Seeding recurrence of follicular thyroid carcinoma after transoral endoscopic thyroidectomy vestibular approach: a case report.

Background: While track recurrence of thyroid cancer following endoscopic and robotic transaxillary surgeries has been reported previously, no such cases have been reported for transoral endoscopic thyroidectomy vestibular approach (TOETVA). This case report describes the first documented case of recurrence of thyroid cancer along the surgical track after TOETVA. Case Description: The patient underwent right lobectomy via TOETVA for a 4 cm follicular thyroid carcinoma (FTC) initially diagnosed as benign follicular nodule on preoperative gun biopsy. The thyroid capsule partially ruptured within the surgical field during surgery. Ultrasonography and computed tomography conducted 27 months after surgery revealed seeding recurrence in the postsurgical thyroid bed, and subcutaneous layers of the right lower lip, submental area, and mid to right upper neck levels I, IIA, and VI. Two-stage re-operation was done to perform completion thyroidectomy, lymph node dissection, and excision of recurrent nodules, which were pathologically confirmed as metastatic FTC. The patient underwent two treatments of radioactive iodine therapy, and post-therapeutic whole-body scintigraphy and computed tomography showed no residual disease. Conclusions: Careful monitoring after TOETVA is essential due to the rare but potential risk of seeding recurrence, especially when the thyroid gland ruptures during surgery. Surgeons should be aware of this atypical complication and be prepared to recommend surgical and/or medical strategies to manage any local seeding of thyroid tissue that may occur.

Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131 I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer : A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer. PATIENTS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria. RESULTS: Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01-1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88-1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78-1.44). CONCLUSIONS: rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.

Clinical Implications of Adding SPECT/CT to Radioiodine Whole-Body Scan in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to determine the usefulness of adding SPECT/CT to radioiodine whole-body scans (WBSs) for the treatment of differentiated thyroid cancer (DTC). PATIENTS AND METHODS: A systematic review and meta-analysis were performed following the PRISMA guidelines (PROSPERO registration: CRD42022341732) to compare the feasibility of conclusive readings and the frequency of changes in treatment plans in patients with DTC undergoing WBS + SPECT/CT versus WBS. MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles concerning thyroid cancer, radioactive iodine, and SPECT/CT or SPECT, published before August 16, 2023. Studies not comparing WBS + SPECT/CT with WBS, those lacking target outcomes, and those not involving human subjects were excluded. The risk of bias was assessed using the RoBANS 2.0 (Risk of Bias Assessment Tool for Nonrandomized Studies) tool. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the quality of evidence and strength of recommendations. RESULTS: A total of 30 studies (prospective n = 9, retrospective n = 21) were included in the meta-analyses. Adding SPECT/CT to WBS was shown to increase conclusive readings for cervical lesions, extracervical lesions, and all regions. Lesion-based analyses showed improvements of 14%, 20%, and 18%, respectively, whereas scan-based analyses showed improvements of 27%, 9%, and 34%. The addition of SPECT/CT to WBS led to changes in 30% of treatment plans after diagnostic scans and 9% of treatment plans after posttherapeutic scans. The quality of evidence and strength of recommendations were low. CONCLUSIONS: Compelling evidence demonstrates that the addition of SPECT/CT to WBS improves lesion localization, diagnostic performance, and therapy plan for patients with DTC.

Establishment and characterization of BMC-PDC-019: a novel patient-derived cell line of EGFR-mutant pulmonary adenocarcinoma transformed into small-cell lung cancer.

Transformed small-cell lung cancer (tSCLC) from EGFR-mutant adenocarcinoma is a rare and aggressive form of lung cancer that can occur when the tumor develops resistance to EGFR targeted therapy and the cancer cells acquire additional genomic alterations that cause them to transform into SCLC. Treatment for tSCLC has not been established yet, and chemotherapy regimens for de novo SCLC are mostly recommended. However, these treatments showed disappointing outcome, and novel anti-cancer agents and immunological approaches are currently being developed. The patient-derived cell line is a critical tool for pre-clinical and translational research, but cell line models for tSCLC are not publicly available from cell banks. The aim of this study was to establish and characterize a novel cell line for tSCLC. Using a lymph-node biopsy tissue from a 58-year-old female patient, whose tumor was EGFR-mutant lung adenocarcinoma progressed on afatinib, we successfully established a cell line, named BMC-PDC-019. The tumor sample and cell line showed a typical expression of SCLC markers, such as CD56 and synaptophysin. The population doubling-time of BMC-PDC-019 cells was 48 h. We examined a range of proliferation-inhibiting effects of anti-cancer drugs currently used for de novo SCLC, using BMC-PDC-019 cells. We concluded that BMC-PDC-019 would be a useful tool for pre-clinical and translational research.

The Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin/Thyroglobulin Antibody Levels and Negative Iodine Scintigraphy: A Systematic Review and Meta-Analysis.

Background: The objective of this study is to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detecting recurrence in patients with differentiated thyroid cancer (DTC) who have negative whole-body scans (WBSs) but elevated serum thyroglobulin (Tg) or thyroglobulin antibody (TgAb) levels. Methods: This systematic review/meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy criteria (International Prospective Register of Systematic Reviews registration number: CRD42022340924). A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases identified articles reporting the diagnostic accuracy of FDG PET/CT for the detection of recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels published between January 2012 and June 2023. Meta-analyses were performed to determine the diagnostic accuracy of FDG PET/CT on the total target population as well as on subgroups stratified by serum Tg or TgAb, and thyrotropin (TSH) stimulation status at the time of FDG PET/CT. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to evaluate the quality of evidence and the strength of recommendations to facilitate translation of the meta-analysis results into practical recommendations for clinical guidelines. Results: A total of 24 studies involving 1988 patients were included for analysis. The overall pooled sensitivity and specificity values were 0.87 (95% confidence interval [CI] = 0.83-0.92; I2 = 75%) and 0.84 (CI = 0.80-0.89; I2 = 44%), respectively. Subgroup analyses revealed no significant differences in the diagnostic accuracy of FDG PET/CT in patients stratified by serum Tg or TgAb levels, and TSH stimulation status at the time of PET/CT. Treatment plans were changed following FDG PET/CT imaging in 40% (CI = 34-47%; I2 = 39%) of cases. The quality level of evidence for using FDG PET/CT was moderate in both sensitivity and specificity according to the GRADE system. Conclusion: There is moderate quality evidence demonstrating the high diagnostic accuracy of FDG PET/CT in detecting recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels. This evidence corroborates the current guidelines' endorsement of FDG PET/CT as a diagnostic tool in such patients.

Current Status of PSMA-Targeted Radioligand Therapy in the Era of Radiopharmaceutical Therapy Acquiring Marketing Authorization.

Prostate-specific membrane antigen (PSMA) is highly expressed in PCa, which gradually increases in high-grade tumors, metastatic tumors, and tumors nonresponsive to androgen deprivation therapy. PSMA has been a topic of interest during the past decade for both diagnostic and therapeutic targets. Radioligand therapy (RLT) utilizes the delivery of radioactive nuclides to tumors and tumor-associated targets, and it has shown better efficacy with minimal toxicity compared to other systemic cancer therapies. Nuclear medicine has faced a new turning point claiming theranosis as the core of academic identity, since new RLTs have been introduced to clinics through the official new drug development processes for approval from the Food and Drug Administration (FDA) or European Medical Agency. Recently, PSMA targeting RLT was approved by the US FDA in March 2022. This review introduces PSMA RLT focusing on ongoing clinical trials to enhance our understanding of nuclear medicine theranosis and strive for the development of new radiopharmaceuticals.

Preclinical biodistribution and dosimetry and human biodistribution comparing 18F-rhPSMA-7 and single isomer 18F-rhPSMA-7.3.

BACKGROUND: Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands such as 18F-rhPSMA-7 are a new class of theranostic agents in clinical development for prostate cancer. We compared preclinical dosimetry and human biodistribution of 18F-rhPSMA-7 with that of single diastereoisomer form, 18F-rhPSMA-7.3. METHODS: Preclinical dosimetry was performed with SCID-mice sacrificed at multiple timepoints (10-300 min) post-injection of 25.6 ± 3.6 MBq 18F-rhPSMA-7 or 28.5 ± 4.8 MBq 18F-rhPSMA-7.3 (n = 3-6 mice per timepoint). Heart, lung, liver, spleen, pancreas, fat, stomach, small intestine, large intestine, kidney, muscle, bone, bladder, testicles, tail, and brain tissue were harvested, and urine and blood samples collected. Percentage of injected dose per gram was calculated. Absorbed doses were estimated with OLINDA/EXM 1.0. 18F-rhPSMA-7 (n = 47) and 18F-rhPSMA-7.3 (n = 33) PET/CT exams were used to estimate human biodistribution. Mean (range) injected activities were 324 (236-424) MBq versus 345 (235-420) MBq, and acquisition times were 84 (42-166) versus 76 (59-122) minutes for 18F-rhPSMA-7 versus 18F-rhPSMA-7.3, respectively. SUVmean was determined for background (gluteal muscle), normal organs (salivary glands, blood pool, lung, liver, spleen, pancreas, duodenum, kidney, bladder, bone) and up to three representative tumour lesions. Qualitative analyses assessed image quality, non-specific blood pool activity, and background uptake in bone/marrow using 3/4-point scales. RESULTS: Preclinical dosimetry revealed that at 3.5 h and 1 h bladder voiding intervals, the extrapolated total effective doses were 26.6 and 12.2 µSv/MBq for 18F-rhPSMA-7 and 21.7 and 12.8 µSv/MBq for 18F-rhPSMA-7.3 respectively. Human biodistribution of both agents was typical of other PSMA-ligands and broadly similar to each other; SUVmean were 16.9 versus 16.2 (parotid gland), 19.6 versus 19.9 (submandibular gland), 2.0 versus 1.9 (blood pool, p < 0.005), 0.7 versus 0.7 (lungs), 7.0 versus 7.3 (liver), 9.1 versus 8.4 (spleen), 32.4 versus 35.7 (kidney), 2.5 versus 2.8 (pancreas), 10.9 versus 11.0 (duodenum), 1.1 versus 1.3 (bone) and 4.6 versus 2.0 (bladder; p < 0.001) for 18F-rhPSMA-7 versus 18F-rhPSMA-7.3, respectively. Tumour SUVmean was higher for 18F-rhPSMA-7.3 (32.5 ± 42.7, n = 63 lesions) than for 18F-rhPSMA-7 (20.0 ± 20.2, n = 89 lesions). CONCLUSIONS: Radiation dosimetry is favourable for both agents. Radiation exposure, assuming a 1 h voiding interval, is less than 5 mSv after injection of 370 MBq. 18F-rhPSMA-7.3 showed significantly lower bladder uptake, and a higher uptake trend in tumours compared with 18F-rhPSMA-7.

Comparative Transcriptome Profiling of Young and Old Brown Adipose Tissue Thermogenesis.

Brown adipose tissue (BAT) is a major site for uncoupling protein 1 (UCP1)-mediated non-shivering thermogenesis. BAT dissipates energy via heat generation to maintain the optimal body temperature and increases energy expenditure. These energetic processes in BAT use large amounts of glucose and fatty acid. Therefore, the thermogenesis of BAT may be harnessed to treat obesity and related diseases. In mice and humans, BAT levels decrease with aging, and the underlying mechanism is elusive. Here, we compared the transcriptomic profiles of both young and aged BAT in response to thermogenic stimuli. The profiles were extracted from the GEO database. Intriguingly, aging does not cause transcriptional changes in thermogenic genes but upregulates several pathways related to the immune response and downregulates metabolic pathways. Acute severe CE upregulates several pathways related to protein folding. Chronic mild CE upregulates metabolic pathways, especially related to carbohydrate metabolism. Our findings provide a better understanding of the effects of aging and metabolic responses to thermogenic stimuli in BAT at the transcriptome level.

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.

Differential Expression of Glucose Transporters and Hexokinases in Prostate Cancer with a Neuroendocrine Gene Signature: A Mechanistic Perspective for 18F-FDG Imaging of PSMA-Suppressed Tumors.

Although the incidence of de novo neuroendocrine prostate cancer (PC) is rare, recent data suggest that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine hallmarks and androgen receptor (AR) suppression in PC. Previous clinical reports indicate that PCs with a phenotype similar to neuroendocrine tumors can be more amenable to imaging by 18F-FDG than by PSMA-targeting radioligands. In this study, we evaluated the association between neuroendocrine gene signature and 18F-FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported 18F-FDG avidity of PSMA-suppressed tumors. Methods: Data-mining approaches, cell lines, and patient-derived xenograft models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes HK1-HK3 and GCK), and PSMA (FOLH1 gene) after AR inhibition and in correlation with neuroendocrine hallmarks. Also, we characterize a neuroendocrine-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no neuroendocrine histopathology. We measured glucose uptake in a neuroendocrine-induced in vitro model and a zebrafish model by nonradioactive imaging of glucose uptake using a fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrated that a neuroendocrine gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR inhibitors, high expression of GCK and low expression of SLC2A12 correlated with neuroendocrine histopathology and PSMA gene suppression. GLUT12 suppression and upregulation of glucokinase were observed in neuroendocrine-induced PC cell lines and patient-derived xenograft models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: A neuroendocrine gene signature in neuroendocrine PC and NELPC associates with a distinct transcriptional profile of GLUTs and hexokinases. PSMA suppression correlates with GLUT12 suppression and glucokinase upregulation. Alteration of 18F-FDG uptake-associated genes correlated positively with higher glucose uptake in AR- and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient preclinical method for monitoring nonradioactive glucose uptake.

Quantitative and Qualitative Analyses of Biodistribution and PET Image Quality of a Novel Radiohybrid PSMA, 18F-rhPSMA-7, in Patients with Prostate Cancer.

Radiohybrid PSMA (rhPSMA) ligands, a new class of theranostic prostate-specific membrane antigen (PSMA)-targeting agents, feature fast 18F synthesis and utility for labeling with radiometals. Here, we assessed the biodistribution and image quality of 18F-rhPSMA-7 to determine the best imaging time point for patients with prostate cancer. Methods: In total, 202 prostate cancer patients who underwent a clinically indicated 18F-rhPSMA-7 PET/CT were retrospectively analyzed, and 12 groups based on the administered activity and uptake time of PET scanning were created: 3 administered activities (low, 222-296 MBq; moderate, 297-370 MBq; and high, 371-444 MBq) and 4 uptake time points (short, 50-70 min; intermediate, 71-90 min; long, 91-110 min; and extra long, ≥111 min). For quantitative analyses, SUVmean and organ- or tumor-to-background ratio were determined for background, healthy organs, and 3 representative tumor lesions. Qualitative analyses assessed overall image quality, nonspecific blood-pool activity, and background uptake in bone or marrow using 3- or 4-point scales. Results: In quantitative analyses, SUVmean showed a significant decrease in the blood pool and lungs and an increase in the kidneys, bladder, and bones as the uptake time increased. SUVmean showed a trend to increase in the blood pool and bones as the administered activity increased. However, no significant differences were found in 377 tumor lesions with respect to the administered activity or uptake time. In qualitative analyses, the overall image quality was stable along with the uptake time, but the proportion rated to have good image quality decreased as the administered activity increased. All other qualitative image parameters showed no significant differences for the administered activities, but they showed significant trends with increasing uptake time: less nonspecific blood activity, more frequent background uptake in the bone marrow, and increased negative impact on clinical decision making. Conclusion: The biodistribution of 18F-rhPSMA-7 was similar to that of established PSMA ligands, and tumor uptake of 18F-rhPSMA-7 was stable across the administered activities and uptake times. An early imaging time point (50-70 min) is recommended for 18F-rhPSMA-7 PET/CT to achieve the highest overall image quality.

Prognostic influence of Korean public medical insurance system on breast cancer patients.

PURPOSE: To investigate the prognostic influence of Korean public medical insurance system on breast cancer patients. METHODS: Data of 1,068 patients with primary invasive breast cancer were analyzed. Korean public medical insurance status was classified into 2 groups: National Health Insurance and Medical Aid. Kaplan-Meier estimator and Cox proportional hazards model were used for survival analysis. RESULTS: The Medical Aid group showed worse prognoses compared to the National Health Insurance group both in overall survival (P = 0.001) and recurrence-free survival (P = 0.006). The Medical Aid group showed higher proportion of patients with tumor size > 2 cm (P = 0.022), more advanced stage (P = 0.039), age > 50 years (P = 0.003), and low education level (P = 0.003). The Medical Aid group showed higher proportion of patients who received mastectomy (P < 0.001) and those who received no radiation therapy (P = 0.013). The Medical Aid group showed a higher rate of distant recurrence (P = 0.014) and worse prognosis for the triple negative subtype (P = 0.006). Medical insurance status was a significant independent prognostic factor in both univariate analysis and multivariate analysis. CONCLUSION: The Medical Aid group had worse prognosis compared to the National Health Insurance group. Medical insurance status was a strong independent prognostic factor in breast cancer. Unfavorable clinicopathologic features could explain the worse prognosis for the Medical Aid group. Careful consideration should be given to medical insurance status as one of important prognostic factors for breast cancer patients.

Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation in Various Cancers.

PURPOSE: Although glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) are known as major proteins involved in the molecular mechanisms for accumulating 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in cancer cells, sometimes, [18F] FDG accumulation cannot be explained by the expression of these two proteins. We investigated the involvement of adenine nucleotide translocase 2 (ANT2), which catalyzes ADP/ATP exchange at the mitochondrial inner membrane, in [18F] FDG accumulation. PROCEDURES: ANT2 expression was evaluated in various cancer cell lines and human cancer tissues (microarrays) using western blot and immunohistochemical (IHC) staining, respectively. The expression levels of ANT2 were compared to [18F] FDG accumulation and pathologic findings, including differentiation grade. Additionally, we modulated ANT2 expression levels using ANT2 siRNA and an ANT2 expression vector in cancer cells and murine xenografted tumors. RESULTS: [18F] FDG accumulation correlated with ANT2 expression in various cancer cell lines; this was not explained by GLUT1 and/or HK2 expression. At both the cell and tissue levels, ANT2 expression was high in less-differentiated or more malignant type of cancers. [18F] FDG accumulation changed according to the modulation of the ANT2 expression level. CONCLUSION: In various cancer cells and tissues, the expression levels of ANT2 explained [18F] FDG accumulation better than those of GLUT1 and HK2. ANT2 can be used as a marker of dedifferentiated pathology and aggressiveness of cancer.

Impact of Breast Cancer Subtypes on Prognosis of Women with Operable Invasive Breast Cancer: A Population-based Study Using SEER Database.

PURPOSE: To determine the prognostic roles of breast cancer subtypes in females with operable invasive breast cancer.Experimental Design: Data of 321,958 patients from Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Breast cancer subtypes were classified into four categories according to the status of hormone receptor (HRc) and HER2: HRc(+)/HER2(-), HRc(+)/HER2(+), HRc(-)/HER2(+), and HRc(-)/HER2(-). RESULTS: Proportions of HRc(+)/HER2(-), HRc(+)/HER2(+), HRc(-)/HER2(+), HRc(-)/HER2(-), and unknown subtype were 70.3%, 9.4%, 3.9%, 10.4%, and 6.0%, respectively. HRc(+)/HER2(-) showed the highest 5-year breast cancer-specific survival (BCSS) rate (95.5%), followed by HRc(+)/HER2(+) (94.1%), HRc(-)/HER2(+) (89.3%), and HRc(-)/HER2(-) (83.1%). HRc(+)/HER2(-) and HRc(+)/HER2(+) showed higher 5-year overall survival (OS) rates (88.4% and 88.2%, respectively) than HRc(-)/HER2(+) and HRc(-)/HER2(-) (83.9% and 76.5%, respectively). HRc(-)/HER2(-) showed the worst BCSS irrespective of race, age, or stage. Although proportions of HRc(-)/HER2(-) in the subgroup with negative event regarding BCSS and OS were 10.4% and 10.2%, respectively, they were 34.2% and 22.7%, respectively, in the subgroup with positive event. Subtype was a significant factor in both univariable and multivariable analyses regarding both BCSS and OS (all P < 0.001). CONCLUSIONS: Breast cancer subtype was a significant independent prognostic factor regarding both BCSS and OS in multivariable analyses. HRc(+) subtypes showed better prognosis compared with HRc(-) subtypes regarding both BCSS and OS. HRc(-)/HER2(+) showed better prognosis than HRc(-)/HER2(-) but worse prognosis than HRc(+) subtypes regarding both BCSS and OS. The triple-negative subtype showed the worst BCSS compared with the other subtypes irrespective of race, age, or stage.

Neuroendocrine differentiation of prostate cancer leads to PSMA suppression.

Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression of FOLH1, NEPC marker genes and SSTR2. We evaluated the transcript abundance for FOLH1 and SSTR2 genes as well as NE markers across 909 tumors. A significant suppression of FOLH1 in NEPC patient samples and AdPC samples with high expression of NE marker genes was observed. We also investigated protein alterations of PSMA and SSTR2 in an NE-induced cell line derived by hormone depletion and lineage plasticity by loss of p53. PSMA is suppressed following NE induction and cellular plasticity in p53-deficient NEPC model. The PSMA-suppressed cells have more colony formation ability and resistance to enzalutamide treatment. Conversely, SSTR2 was only elevated following hormone depletion. In 18 NEPC patient-derived xenograft (PDX) models we find a significant suppression of FOLH1 and amplification of SSTR2 expression. Due to the observed FOLH1-supressed signature of NEPC, this study cautions on the reliability of using PMSA as a target for molecular imaging of NEPC. The observed elevation of SSTR2 in NEPC supports the possible ability of SSTR2-targeted imaging for follow-up imaging of low PSMA patients and monitoring for NEPC development.

Prostate-Specific Membrane Antigen PET Imaging in Prostate Cancer: Opportunities and Challenges.

The aim of this systematic review was to describe the characteristics of prostate-specific membrane antigen (PSMA)-targeting PET and their clinical applications in prostate cancer patients. There have been major strides in the design, synthesis of PSMA-targeting PET tracers over the past several years. PSMA-targeting PET tracers can be categorized, according to positron emitters and targeting strategies for the PSMA. The majority of PSMA PET studies has been focused on patients with biochemical recurrence, but additional values of PSMA PET have also been investigated for use in primary staging, treatment planning, response evaluation, and PSMA radioligand therapy. PSMA PET is expected to bring improvements in the management of patients, but the impact of improved diagnosis by PSMA on overall survival remains unanswered. Many challenges still await PSMA PET to expedite the use in the clinical practice. At this early stage, prospective multicenter trials are needed to validate the effectiveness and usefulness of PSMA PET.

Findings of Single-Photon Emission Computed Tomography and Its Relation with Quantitative Coronary Angiography in Patients with Significant Stenosis of the Left Main Coronary Artery.

Objective: Unrecognized left main coronary artery disease (LMCD) is often fatal; however, accuracy of non-invasive tests for diagnosing LMCD is still unsatisfactory. This study was performed to elucidate single-photon emission computed tomography (SPECT) detection of LMCD using quantitative coronary angiography (QCA) data. Materials and Methods: Fifty-five patients (39 men; mean age, 68.1 ± 10.9 years) diagnosed with significant left main (LM) stenosis (≥ 50%) by invasive coronary angiography (ICA) were retrospectively reviewed. All study patients underwent SPECT with pharmacologic stress within 30 days of ICA. All coronary lesions were quantified via QCA, and SPECT findings were compared with QCA results. Results: Only four patients (7.3%) had isolated LMCD; all others had combined significant stenosis (≥ 70%) of one or more other epicardial coronary arteries. Patients with more severe coronary artery disease tended to have higher values for summed difference scores in a greater number of regions, but the specific pattern was not clearly defined. Summed stress score of SPECT did not differ according to LM stenosis severity. Only three patients (5.4%) had a typical LM pattern of reversible perfusion defect on SPECT. A significant negative linear correlation between stenosis severity and stress perfusion percent was found in the left anterior descending artery region (r = -0.455, p < 0.001) but not in the left circumflex artery. Conclusion: Single-photon emission computed tomography findings were heterogeneous, not specific and poorly correlated to QCA data in patients with significant LMCD. This may be due to highly prevalent significant stenosis of other epicardial coronary arteries.

Influence of Androgen Deprivation Therapy on the Uptake of PSMA-Targeted Agents: Emerging Opportunities and Challenges.

Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer.

Incidentally Detected Small Intestine Intussusception Caused by Primary Small Intestine Carcinoma on 18F-FDG PET/CT.

Small intestine intussusception in adults is a rare condition mainly caused by primary or metastatic small intestine malignancy. Here, we present a 72-year-old male patient who was diagnosed with small intestine cancer that was presented as small intestine intussusception on hybrid 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). The patient was initially referred for an abnormality on a chest radiography and severe anemia. FDG PET/CT showed the lung lesion in the right upper lobe of lung as a high FDG uptake mass. Accidentally, FDG PET demonstrated another intense hypermetabolic intraluminal lesion in the small intestine accompanied with intussusception shown as a circumferential hypermetabolic wall. By pathologic examination, the patient was diagnosed as primary small intestine cancer with lung metastasis. This case highlights usefulness of hybrid FDG PET/CT to identify unexpected malignancy.

Additional Value of Brachial-Ankle Pulse Wave Velocity to Single-Photon Emission Computed Tomography in the Diagnosis of Coronary Artery Disease.

AIM: The aim of this study was to investigate whether information on arterial stiffness can improve the value of single-photon emission computed tomography (SPECT) in the detection of obstructive coronary artery disease (CAD). METHODS: A total of 233 patients (age: 62.2±10.8 years, 60.3% males) with detected ischemia on SPECT undergoing invasive coronary angiography (ICA) and brachial-ankle pulse wave velocity (baPWV) measurement within a month was retrospectively reviewed. RESULTS: Of the 233 patients, 190 (81.5%) had obstructive CAD (≥50% luminal stenosis). The difference in baPWV according to the presence of obstructive CAD was significant in patients in the mild ischemia group [summed stress score (SSS): 4-8] (1,770±364 cm versus 1,490±328 cm, p＜0.001) but not in the moderate (SSS: 9-13) or severe (SSS: ≥14) ischemia groups (p＞0.05 for each). Receiver operating characteristic curve analyses showed that the diagnostic value of baPWV for obstructive CAD was significant only in patients in the mild ischemia group (area under curve: 0.714; p=0.001) but not in the moderate or severe ischemia groups (p＞0.05 for each). Adding information on baPWV to SPECT results and clinical parameters significantly increased diagnostic accuracy in the detection of obstructive CAD in patients with mild ischemia (integrated discrimination improvement p=0.006) but not in those with moderate or severe ischemia on SPECT (p＞0.05 for each). CONCLUSIONS: The results of this study suggest that baPWV may have additional value to SPECT for the detection of obstructive CAD, especially in patients with mild ischemia on SPECT.