Mitochondrial DNA mosaicism in normal human somatic cells.

Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10-8 per base pair) and a turnover frequency of 10-20 per year, which are fundamental components shaping the landscape of mtDNA mosaicism over a lifetime. The expansion of mtDNA-truncating mutations toward homoplasmy was substantially suppressed. Our findings provide comprehensive insights into the origins, dynamics and functional consequences of mtDNA mosaicism in human somatic cells.

Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.

Widespread somatic L1 retrotransposition in normal colorectal epithelium.

Throughout an individual's lifetime, genomic alterations accumulate in somatic cells1-11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12-14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

SP-1154, a novel synthetic TGF-ß inhibitor, alleviates obesity and hepatic steatosis in high-fat diet-induced mice.

OBJECTIVE: Obesity-induced inflamed visceral adipose tissue (VAT) secretes pro-inflammatory cytokines thereby promoting systemic inflammation and insulin resistance which further exacerbate obesity-associated nonalcoholic fatty liver disease (NAFLD). Transforming growth factor (TGF)-ß /Smad3 signaling plays a crucial role in the inflammatory events within the VAT. Here, we investigate whether SP-1154, a novel synthetic verbenone derivative, can inhibit TGF-ß/Smad3 signaling thereby exhibiting a therapeutic effect against obesity-induced inflamed VAT and subsequent NAFLD in high-fat diet-induced mice. METHODS: NAFLD was induced by a high-fat diet (60% fat) for 20 weeks using the male C57BL/6 mice. SP-1154 (50 mg/kg) was orally given daily for 20 weeks. In vivo VAT- and systemic inflammation were measured by using 18F-fluorodeoxyglucose positron emission tomography and C-reactive protein levels. Both insulin tolerance- and glucose tolerance test were performed to assess the status of insulin resistance and glucose intolerance. Histological and molecular analyses were performed on harvested liver and VAT. KEY FINDINGS: SP-1154 inhibited TGF-ß/Smad3 signaling pathway and remarkably suppressed high-fat diet-induced VAT inflammation and its related systemic inflammation. Furthermore, SP-1154 significantly improved insulin sensitivity with glucose homeostasis and reduced hepatic steatosis. SP-1154 significantly improves VAT inflammation and obesity-related NAFLD. CONCLUSION: Our novel findings support the potential use of SP-1154 as a therapeutic drug for obesity and its related NAFLD by targeting the inflamed VAT.

Chronic physical exercise alleviates stress-associated amygdala metabolic activity in obese women: A prospective serial 18F-FDG PET/CT study.

Background: Psychological stress is considered as a major risk factor for cardiovascular disease (CVD). Chronic exercise is known to reduce CVD risk partly through attenuating psychological stress. Obesity has been linked with increased levels of psychological stress. We aimed to prospectively evaluate whether physical exercise could alleviate stress-associated amygdala metabolic activity, assessed by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in women with obesity. Material and methods: A total of 43 participants were enrolled in this study. Twenty-three obese women were participated in a physical exercise program 5 days per week for 3 months. The exercise program consisted of aerobic exercise and resistance training. Serial 18F-FDG PET/CT was taken before the start of physical exercise program (baseline) and after finishing the program (post-exercise). A total of 20 participants who underwent 18F-FDG PET/CT for general health check-up were enrolled as non-obese control group. Brain amygdala activity (AmygA) was calculated as maximum standardized uptake value (SUVmax) of amygdala normalized to mean SUV of temporal lobe. Results: Chronic physical exercise significantly reduced AmygA and improved body adiposity and systemic inflammation. AmygA was highest in baseline, intermediate in post-exercise, and lowest in non-obese control group (0.76 ± 0.17, 0.61 ± 0.1, 0.52 ± 0.09, p < 0.001). Furthermore, physical exercise also abrogated the association of AmygA with systemic inflammation. Conclusions: Chronic physical exercise reduced stress-associated amygdala metabolic activity and broke its association with systemic inflammation in obese women. This study could explain the putative mechanism underlying the health beneficial effect of exercise on CVD via attenuation of stress neurobiology.

Changes in treatment intent and target definition for preoperative radiotherapy after 18F-Fluorodeoxyglucose positron emission tomography in rectal cancer: A Meta-analysis.

PURPOSE: To evaluate the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on changes in treatment plan and target definition for preoperative radiotherapy in patients with rectal cancer. METHODS: Embase, PubMed, and Cochrane Library were searched up to November 2020 for all studies investigating the role of preoperative FDG PET in patients who underwent neoadjuvant radiotherapy before curative-intent surgery. The proportion of patients whose treatment plan (curative vs. palliative intent) or target definition was changed after FDG PET was analyzed. A random-effects model was used for pooled analysis. The change in target definition was compared between conventional radiological imaging-based target volume [gross tumor volume (GTV) or planning target volume (PTV)] and PET-based target volume (GTV or PTV) using the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 336 patients from twelve studies were included. In eight studies, PET changed either the treatment intent or target definition in 24.8% of patients (95% CI 15.1% to 37.9%, I2 = 69%). In ten studies, the PET-based GTV was lower than the conventional imaging-based target volume (SMD -7.0, 95% CI -1.39 to -0.01). However, there was no significant difference between conventional imaging-based and PET-based PTV (SMD -0.07, 95% CI -0.75 to 0.62). In six studies evaluating the initial staging based on PET, the initial staging (nodal or metastasis status) was changed in 53 of 229 patients (23.1%). Newly detected or additional distant metastases were identified in 22 patients (9.6%) after FDG PET. CONCLUSION: The use of FDG PET influences radiotherapy planning in a fourth of patients with rectal cancer. FDG PET can provide additive information for accurate tumor delineation, although PET-based PTV did not significantly change. These findings suggest that FDG PET may be beneficial to patients with rectal cancer before establishing a radiotherapy plan.

Dissecting single-cell genomes through the clonal organoid technique.

The revolution in genome sequencing technologies has enabled the comprehensive detection of genomic variations in human cells, including inherited germline polymorphisms, de novo mutations, and postzygotic mutations. When these technologies are combined with techniques for isolating and expanding single-cell DNA, the landscape of somatic mosaicism in an individual body can be systematically revealed at a single-cell resolution. Here, we summarize three strategies (whole-genome amplification, microdissection of clonal patches in the tissue, and in vitro clonal expansion of single cells) that are currently applied for single-cell mutational analyses. Among these approaches, in vitro clonal expansion, particularly via adult stem cell-derived organoid culture technologies, yields the most sensitive and precise catalog of somatic mutations in single cells. Moreover, because it produces living mutant cells, downstream validation experiments and multiomics profiling are possible. Through the synergistic combination of organoid culture and genome sequencing, researchers can track genome changes at a single-cell resolution, which will lead to new discoveries that were previously impossible.

Clustering subtypes of breast cancer by combining immunohistochemistry profiles and metabolism characteristics measured using FDG PET/CT.

BACKGROUND: The aim of this study was to investigate the effect of combining immunohistochemical profiles and metabolic information to characterize breast cancer subtypes. METHODS: This retrospective study included 289 breast tumors from 284 patients who underwent preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT). Molecular subtypes of breast cancer were classified as Hormonal, HER2, Dual (a combination of both Hormonal and HER2 features), and triple-negative (TN). Histopathologic findings and immunohistochemical results for Ki-67, EGFR, CK 5/6, and p53 were also analyzed. The maximum standardized uptake value (SUV) measured from FDG PET/CT was used to evaluate tumoral glucose metabolism. RESULTS: Overall, 182, 24, 47, and 36 tumors were classified as Hormonal, HER2, Dual, and TN subtypes, respectively. Molecular profiles of tumor aggressiveness and the tumor SUV revealed a gradual increase from the Hormonal to the TN type. The tumor SUV was significantly correlated with tumor size, expression levels of p53, Ki-67, and EGFR, and nuclear grade (all p < 0.001). In contrast, the tumor SUV was negatively correlated with the expression of estrogen receptors (r = - 0.234, p < 0.001) and progesterone receptors (r = - 0.220, p < 0.001). Multiple linear regression analysis revealed that histopathologic markers explained tumor glucose metabolism (adjusted R-squared value 0.238, p < 0.001). Tumor metabolism can thus help define breast cancer subtypes with aggressive/adverse prognostic features. CONCLUSIONS: Metabolic activity measured using FDG PET/CT was significantly correlated with the molecular alteration profiles of breast cancer assessed using immunohistochemical analysis. Combining molecular markers and metabolic information may aid in the recognition and understanding of tumor aggressiveness in breast cancer and be helpful as a prognostic marker.

Stress-Related Amygdala Metabolic Activity Is Associated With Low Bone Mineral Density in Postmenopausal Women: A Pilot 18F-FDG PET/CT Study.

Background: Psychological stress is associated with postmenopausal osteoporosis. However, the underlying mechanism of stress-related brain neural activity with osteoporosis is not fully elucidated. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is an established method to evaluate the metabolic activity of brain amygdala, a region involved in stress. We aimed to evaluate the relationship between metabolic activity of amygdala (AmygA) and osteoporosis in postmenopausal women. Materials and Methods: A total of 115 postmenopausal women who underwent 18F-FDG PET/CT and dual-energy X-ray absorptiometry for routine health screening were enrolled in this study. AmygA was defined as the maximum standardized uptake value (SUVmax) of amygdala divided by the mean SUV of temporal lobe. The levels of psychological stress were measured using the Psychosocial Well-being Index-Short Form (PWI-SF). Results: The participants with osteoporosis exhibited significantly higher AmygA than without osteoporosis (0.81 ± 0.16 vs. 0.61 ± 0.13, p < 0.001). The AmygA value of 0.69 was suggested as an optimal cut-off value to identify participant with osteoporosis (sensitivity; 79.1%, specificity; 83.3%, area under the curve; 0.841, p < 0.001). Furthermore, AmygA showed significant association with osteoporosis in postmenopausal woman by multivariate analysis. Psychological stress scale (PWI-SF) was well correlated with AmygA and AmygA was highest in high stress risk-, intermediate in moderate stress risk-, and lowest in healthy group. Conclusions: AmygA measured by 18F-FDG PET/CT is associated with osteoporosis in postmenopausal women. Our results provide the possibility that stress-related neurobiological activity involving amygdala is linked with postmenopausal osteoporosis.

SlHair2 Regulates the Initiation and Elongation of Type I Trichomes on Tomato Leaves and Stems.

Trichomes are hair-like structures that are essential for abiotic and biotic stress responses. Tomato Hair (H), encoding a C2H2 zinc finger protein, was found to regulate the multicellular trichomes on stems. Here, we characterized Solyc10g078990 (hereafter Hair2, H2), its closest homolog, to examine whether it was involved in trichome development. The H2 gene was highly expressed in the leaves, and its protein contained a single C2H2 domain and was localized to the nucleus. The number and length of type I trichomes on the leaves and stems of knock-out h2 plants were reduced when compared to the wild-type, while overexpression increased their number and length. An auto-activation test with various truncated forms of H2 using yeast two-hybrid (Y2H) suggested that H2 acts as a transcriptional regulator or co-activator and that its N-terminal region is important for auto-activation. Y2H and pull-down analyses showed that H2 interacts with Woolly (Wo), which regulates the development of type I trichomes in tomato. Luciferase complementation imaging assays confirmed that they had direct interactions, implying that H2 and Wo function together to regulate the development of trichomes. These results suggest that H2 has a role in the initiation and elongation of type I trichomes in tomato.

Association of Inflammatory Metabolic Activity of Psoas Muscle and Acute Myocardial Infarction: A Preliminary Observational Study with 18F-FDG PET/CT.

Inflamed skeletal muscle promotes chronic inflammation in atherosclerotic plaques, thereby contributing to the increased risk of coronary artery disease (CAD). In this study, we evaluated the metabolic activity of psoas muscle, using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), and its association with carotid artery inflammation and acute myocardial infarction (AMI). In total, 90 participants (32 AMI, 33 chronic stable angina (CSA), and 25 control) were enrolled in this prospective study. Metabolic activity of skeletal muscle (SM) was measured by using maximum standardized uptake value (SUVmax) of psoas muscle, and corresponding psoas muscle area (SM area) was also measured. Carotid artery inflammation was evaluated by using the target-to background ratio (TBR) of carotid artery. SM SUVmax was highest in AMI, intermediate in CSA, and lowest in control group. SM SUVmax was significantly correlated with carotid artery TBR and systemic inflammatory surrogate markers. Furthermore, SM SUVmax was independently associated with carotid artery TBR and showed better predictability than SM area for the prediction of AMI. Metabolic activity of psoas muscle assessed by 18F-FDG PET/CT was associated with coronary plaque vulnerability and synchronized with the carotid artery inflammation in the participants with CAD. Furthermore, it may also be useful to predict AMI.

Effect of Exercise on Inflamed Psoas Muscle in Women with Obesity: A Pilot Prospective 18F-FDG PET/CT Study.

Obesity increases inflammation in skeletal muscle thereby promoting systemic inflammation which leads to increased risk of cardiometabolic disease. This prospective study aimed to evaluate whether the metabolic activity of psoas muscle (PM) was associated with systemic inflammation, and whether physical exercise could reduce the PM metabolic activity evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in women with obesity. A total of 23 women with obesity who participated in a 3-month physical exercise program were enrolled. 18F-FDG PET/CT was performed before the start of the program (baseline) and after completion of the program. The maximum standardized uptake value of psoas muscle (PM SUVmax) was used for the PM metabolic activity. The SUVmax of spleen and bone marrow, and the high-sensitivity C-reactive protein were used to evaluate the systemic inflammation. At baseline, PM SUVmax was strongly correlated with the systemic inflammation. The exercise program significantly reduced the PM SUVmax, in addition to adiposity and systemic inflammation. Furthermore, we found that the association between PM SUVmax and the systemic inflammation disappeared after completion of the exercise program. In women with obesity, PM SUVmax, assessed by 18F-FDG PET/CT, was associated with obesity-induced systemic inflammation and exercise reduced the PM SUVmax and eliminated its association with systemic inflammation.

Metabolic Activity of Visceral Adipose Tissue Is Associated with Metastatic Status of Lymph Nodes in Endometrial Cancer: A 18F-FDG PET/CT Study.

Obesity contributes to increased cancer incidence and aggressiveness in patients with endometrial cancer. Inflamed metabolic activity of visceral adipose tissue (VAT) is regarded as a key underlying mechanism of adverse consequences of obesity. The aim of this study was to investigate the association between inflammatory metabolic activity of VAT evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and metastatic status of lymph nodes (LN) in patients with endometrial cancer. In total, 161 women with newly diagnosed endometrial cancer, who received preoperative 18F-FDG PET/CT, were enrolled. VAT inflammatory metabolic activity was defined as V/S ratio and measured from the maximum standardized uptake value (SUVmax) of VAT normalized to the SUVmax of subcutaneous adipose tissue (SAT). The positive LN metastasis group exhibited a significantly higher V/S ratio than the negative LN metastasis group. Systemic inflammatory surrogate markers including high sensitivity C-reactive protein, spleen SUVmax, and bone marrow SUVmax were also higher in the LN metastasis group than in the negative LN metastasis group, showing significant correlations with V/S ratio. In multivariate logistic regression analysis, V/S ratio was independently associated with LN metastasis. V/S ratio is independently associated with the LN metastasis status in patients with endometrial cancer. This finding could be useful as a potential surrogate marker of obesity-induced VAT inflammation associated with tumor aggressiveness.

Recent Survey of Effective Doses of F-18 FDG Torso PET/CT in Korea and the Current Recommendations for CT Protocols of PET/CT.

PURPOSE: This study aimed to construct a database of the effective doses (ED) from F-18 fluorodeoxyglucose (FDG) torso positron emission tomography/computed tomography (PET/CT) in Korea to provide data that supports the reduction of the CT dose of PET/CT and optimization of PET/CT protocols in Korea. METHODS: We investigated data of ED and CT parameters of FDG PET/CT. The data were analyzed by body weight groups. RESULTS: A total of 31 hospitals participated in the survey (99 adults). The mean total EDs (± SD) were 8.77 ± 2.76, 10.93 ± 3.14, and 12.57 ± 3.79 mSv for the 55-, 70-, and 85-kg groups, respectively. The FDG EDs were 4.80 ± 0.98, 6.05 ± 1.15, and 6.89 ± 1.52 mSv, and the CT EDs were 4.00 ± 2.12, 4.88 ± 2.51, and 5.68 ± 2.89 mSv, respectively. Of the enrolled hospitals, 54.5% used ultra-low-dose CT protocols, and their CT ED was significantly lower than low-dose CT group in all groups (2.9 ± 1.0, 3.2 ± 1.1, and 3.3 ± 1.0 mSv vs. 6.6 ± 1.6, 7.2 ± 2.1, and 7.9 ± 2.2 mSv, all p < 0.001, respectively). In the ultra-low-dose CT group, the CT ED with the iterative reconstruction was significantly lower than that of CT without iterative reconstruction in the 55-kg group (2.4 ± 0.9 vs. 3.3 ± 0.9, p = 0.04). CONCLUSIONS: These results and current recommendations can be helpful for optimizing PET/CT diagnostic reference level (DRL) and reducing unnecessary PET/CT radiation exposure.

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.

Prognostic Value of Metabolic Information in Advanced Gastric Cancer Using Preoperative 18F-FDG PET/CT.

PURPOSE: This study evaluated the usefulness of semiquantitative and volumetric PET parameters for predicting prognosis in patients with advanced gastric cancer (AGC). METHODS: We enrolled 213 patients who underwent 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) prior to curative surgery for AGC. Maximum standardized uptake value (SUVmax) and tumor-to-liver uptake ratio (TLR) were measured in all patients. Metabolic tumor volume (MTV) and total lesion glycolysis were measured in volume-measurable patients. For further quantification of FDG uptake, we developed PET prognostic scores by combining SUVmax and MTV (1: low SUVmax/low MTV; 2: high SUVmax/low MTV; 3: high SUVmax/high MTV). Comparison of PET parameters between recurrence and non-recurrence groups was performed. Univariate and multivariate analyses for recurrence-free survival (RFS) and overall survival (OS) were subsequently performed. RESULTS: The recurrence rate was 32.4% (69/213 patients). Mean SUVmax and mean MTV of the recurrence group were significantly higher than those of the non-recurrence group (p = 0.026 and p = 0.025). TLR showed marginal significance (p = 0.051). In multivariate analysis for RFS including all patients, SUVmax (p = 0.022), TLR (p = 0.010), and PET score (p = 0.003) were independent prognostic factors. In post hoc analysis of PET score, significant differences in RFS were observed between PET scores 2 and 3 as well as scores 1 and 3. No significant difference in RFS was observed between scores 1 and 2. Only PET score was statistically significant for OS in univariate analysis. None of the PET parameters were statistically significant for OS in multivariate analysis. CONCLUSION: High SUVmax and high MTV of the primary tumor suggest a high risk of recurrence for AGC patients. Even if SUVmax is similar, the prognosis may vary depending on MTV. Combining PET parameters results in a better prediction for prognosis.

Composite criteria using clinical and FDG PET/CT factors for predicting recurrence of hepatocellular carcinoma after living donor liver transplantation.

OBJECTIVES: Fluorodeoxyglucose (FDG) PET/CT is effective for predicting recurrence of hepatocellular carcinoma after liver transplantation. This study aimed to design composite criteria for predicting post-transplantation recurrence using clinical and FDG PET/CT factors. METHODS: We retrospectively enrolled 239 patients who underwent living donor transplantation in two independent centers between 2005 and 2013. On PET, maximum tumor-to-background ratio (TBRmax) was measured. Significant predictors for recurrence were selected by logistic regression and survival analyses. With varying cutoff values for the selected factors, composite criteria were designed to maximize the predictive performance for recurrence, and tenfold cross-validation was performed. Predictive values were compared between the composite criteria and the conventional recipient selection criteria. RESULTS: Tumor size, number, alpha-fetoprotein, and TBRmax were selected as significant predictors in both logistic regression and multivariate survival analyses. In combination of these factors, the highest diagnostic performance was sensitivity of 75.7% and specificity of 88.5% with cutoff values of tumor size < 6.0 cm, tumor number < 8, alpha-fetoprotein < 465 ng/mL, and TBRmax < 2.8. The composite criteria exhibited the highest performance for predicting recurrence and recurrence-free survival among the tested criteria including conventional ones. CONCLUSIONS: The composite criteria adding FDG PET findings to clinical factors are effective in selecting appropriate liver cancer patients who are candidates for liver transplantation. KEY POINTS: • In patients with HCC, tumor uptake on FDG PET/CT, tumor size, number, and serum AFP level are recognized individual predictors for tumor recurrence after LT. • A composite criterion set, combining tumor size, number, serum AFP level, and maximum tumor-to-background ratio (TBR max ), predicts post-LT recurrence most effectively when compared with conventional criteria sets in selecting candidates for living donor LT.

Predictive Value of Preoperative Volume-Based 18F-2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography/Computed Tomography Parameters in Patients with Resectable Lung Adenocarcinoma.

PURPOSE: This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma. METHODS: We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method. RESULTS: The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean ± SD SUVmax, MTV30%, and TLG30% of the entire cohort were 4.79 ± 2.94, 19.45 ± 24.85, and 56.43 ± 101.88, respectively. The cut-off values of MTV30% and TLG30% for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV30% patients compared with 86.2% in high-MTV30% patients (p = 0.018) and 96.0% in low-TLG30% patients compared with 88.5% in high-TLG30% patients (p < 0.001). On univariate and multivariate analysis, TLG30% (HR, 2.828, p < 0.001; HR, 2.738, p < 0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS). CONCLUSION: TLG30% value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.