Clinical Circulating Tumor DNA Testing for Precision Oncology / Journal of the Korean Cancer Association, 대한암학회지

Circulating tumor DNA (ctDNA) is the portion of the cell-free DNA in the blood of cancer patients released from tumor cells via apoptosis, necrosis, or active release. From 10 mL of blood, the 4-5 mL of plasma obtained from a cancer patient contains 5-10 ng/mL of ctDNA. The plasma contains not only ctDNA of tumor origin, but also DNA from normal cells or clonal hematopoiesis. Another characteristic of ctDNA is its rapid clearance from circulation; it has a half-life of 16 minutes to 2.5 hours. Obtaining reliable results from ctDNA requires the application and approval of standardized clinical validation guidelines; however, the status of numerous ctDNA tests currently varies. The clinical use of ctDNA testing should be carefully considered based on the test’s specific needs and characteristics. Here we provide the different characteristics of ctDNA tests and information regarding their validation and approval status.

Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study

Background@#In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19). @*Methods@#This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023. @*Results@#Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27–3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71–5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22–0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15–0.91) reduced the occurrence of adverse events. @*Conclusion@#The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.

Preliminary Study for Quantitative Assessment of Sacroiliitis Activity Using Bone SPECT/CT: Comparison of Diagnostic Performance of Quantitative Parameters / 대한핵의학회잡지

Purpose@#We compared the feasibility of quantitative analysis methods using bone SPECT/CT with those using planar bone scans to assess active sacroiliitis. @*Methods@#We retrospectively reviewed whole-body bone scans and pelvic bone SPECT/CTs of 8 patients who had clinically confirmed sacroiliitis and enrolled 24 patients without sacroiliitis as references. The volume of interest of each sacroiliac joint, including both the ilium and sacrum, was drawn. Active arthritis zone (AAZ) was defined as the zone of voxels with higher SUV than sacral mean SUV within the VOI of SI joint. Then, the following SPECT/CT quantitative parameters, SUVmax (maximum SUV), SUV50% (mean SUV in highest 50% of SUV), and SUV-AAZ, and the ratio of those values to sacral mean SUV (SUVmax/S, SUV50%/S, SUV-AAZ/S) were calculated. For the planar bone scan, the mean count ratio of SI joint/sacrum (SI/S) was conventionally measured. @*Results@#Most of the SPECT/CT parameters of the sacroiliitis group were significantly higher than the normal group, whereas SI/S of the planar bone scan was not significantly different between the two groups. In receiver operating characteristic curve analysis, SUV-AAZ/S showed the highest AUC of 0.992, followed by SUV50%/S and SUVmax/S. All ratio parameters of the SPECT/CT showed higher AUC values than the SUV parameters of SI joint or SI/S of the planar scan. @*Conclusions@#The quantitative analyses of bone SPECT/CT showed better performance in assessing active sacroiliitis than the planar bone scan. SPECT/CT parameters using the ratio of the SI joint to sacrum showed more favorable results than SUV parameters such as SUVmax, SUV50%, and SUV-AAZ.

Transient Mutism Related to Capecitabine-Induced Acute Toxic Leukoencephalopathy

Capecitabine, a precursor of 5-fluorouracil (5-FU), is a well-tolerated and safe chemotherapy that has been used to treat breast, pancreatic, and colorectal cancers. Albeit rare, both 5-FU and capecitbine have been reported to be associated with acute central nervous system toxicity, including cerebellar dysfunction, posterior reversible encephalopathy syndrome, and transient leukoencephalopathies. Here we present a case of 32-year-old female, demonstrating transient mutism related to capecitabine induced acute toxic leukoencephalopathy.

Cooperative Subtype Switch of Thyroid Hormone Receptor and Nuclear Receptor Corepressor Related Epithelial–Mesenchymal Transition in Papillary Thyroid Cancer

Background and Objectives@#Although thyroid hormones affect human cancer progression, the regulatory mechanism of thyroid hormone receptors in carcinogenesis has not been elucidated. This study aimed to evaluate the expression pattern of the thyroid hormone receptor (TR) and its corepressors, and to investigate the clinical and biological functions of TR. @*Materials and Methods@#Transcriptomic and clinical data for thyroid cancer were downloaded from The Cancer Genome Atlas. Paraffin-embedded tissue sections from patients who underwent thyroidectomy were used for immunohistochemistry. BCPAP cells were treated with T3 to investigate the thyroid hormone target genes. Thyroid hormone receptor alpha (THRA) and Thyroid hormone receptor beta (THRB) were knocked down by transient siRNA transfection. @*Results@#THRA and THRB expression was lower in thyroid cancer tissues than in normal tissues. However, strong focal staining of TRβ was observed in the invasive front. High THRB expression was associated with high Silencing Mediator for Retinoid or Thyroid hormone receptor (SMRT) expression, older age, a high MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) score, more aggressive histological subtypes, more frequent extra-thyroidal extension, and advanced TNM stage. THRB expression was positively correlated with Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A), L1 Cell Adhesion Molecule (L1CAM), and Lysyl Oxidase (LOX) expression. Thyroid hormone-induced HIF1A, L1CAM, and LOX upregulation was abolished by siTHRB but not siTHRA in BCPAP cells. High SMRT and high THRB groups (SMRT/THRB) presented more aggressive clinical features and showed an upregulation of HIF1A, L1CAM, and LOX, as well as of epithelial-mesenchymal transition (EMT)-related genes, causing changes in the tumor microenvironment. @*Conclusion@#Cooperative subtype switching from NCOR1/THRA to SMRT/THRB was thus related to aggressive clinical and molecular features, possibly related to EMT and EMT-related tumor microenvironment.

Cancer Survivors with Low Hand Grip Strength Have Decreased Quality of Life Compared with Healthy Controls: The Korea National Health and Nutrition Examination Survey 2014–2017 / 가정의학회지

Background@#Cancer survivors experience decreased physical function and reduced muscle strength, which leads to lower quality of life (QOL). The hand grip strength (HGS) can be a predictor of poor health-related QOL as a parameter of sarcopenia. The purpose of this study was to investigate the relationship between low HGS and QOL in cancer survivors and healthy controls. @*Methods@#We analyzed 392 cancer survivors and 1,176 healthy controls from the Korea National Health and Nutrition Examination Survey, 2014–2017. We defined low HGS as 2 standard deviation values for healthy young Korean adults from a previous study. QOL was evaluated using the European Quality of Life Scale-Five Dimensions. A complex sample logistic regression model was used to assess the relationship between each dimension of low HGS and QOL. @*Results@#The odds ratios (ORs) for decreased QOL were significantly higher in male cancer survivors with low HGS on self-care (OR, 8.51; 95% confidence interval [CI], 1.69–42.83) and usual activities (OR, 6.63; 95% CI, 1.22–36.03). The ORs for problems in mobility (OR, 5.87; 95% CI, 2.04–16.91), usual activities (OR, 14.46; 95% CI, 3.84–54.44), pain/discomfort (OR, 4.90; 95% CI, 2.00–12.01), and anxiety/depression (OR, 6.43; 95% CI, 2.16–19.12) were significantly high in female cancer survivors with low HGS. However, healthy controls showed no significant relationship between low HGS and QOL. @*Conclusion@#For cancer survivors, low HGS was associated with poor QOL in some domains. Strategies to increase muscle strength must be considered to improve the QOL of cancer survivors.

Effect of Increasing Tobacco Prices on Stages of Smoking Cessation: A Korean Nationwide Data Analysis / 가정의학회지

Background@#In 2015, tobacco prices significantly increased in Korea as part of the government’s smoking cessation policy. This study examined the changes in the stages of smoking cessation among Korean male smokers before and after the implementation of the tobacco price policy, and identified the predictors of such changes. @*Methods@#The study population comprised 3,533 male current smokers (age ≥19 years) who participated in the Korea National Health and Nutrition Survey in 2012, 2013, 2015, and 2016. Current smokers were defined as persons who had smoked ≥100 cigarettes during their lifetime and are continuing to smoke. In accordance with the transtheoretical model, smokers were classified into the precontemplation stage (no plan to quit), contemplation stage, and preparation stage (planning to quit within 6 months). We examined the changes in the smoking cessation stages before and after the implementation of the policy. Multivariate logistic regression analysis was conducted to identify factors related to the likelihood of continuing smoking, after adjustments for potential confounders. @*Results@#Immediately after the policy implementation, the percentage of smokers in the precontemplation stage decreased from 65.6% to 60.8% (P=0.014). However, this effect was temporary. Significant risk factors for remaining in the precontemplation stage were older age (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.002–1.018; P=0.004), being in the lowest income quartile (OR, 1.226; 95% CI, 1.001–1.502; P=0.049), and manual worker or unemployed status (OR, 1.256; 95% CI, 1.036–1523; P=0.020). @*Conclusion@#Increasing tobacco prices only temporarily change the stage of smoking cessation among Korean male smokers.

Combined Effects of Depression and Chronic Disease on the Risk of Mortality: The Korean Longitudinal Study of Aging (2006-2016)

Background@#The prevalence of depression is much higher in people with chronic disease than in the general population. Depression exacerbates existing physical conditions, resulting in a higher-than-expected death rate from the physical condition itself. In our aging society, the prevalence of multimorbid patients is expected to increase; the resulting mental problems, especially depression, should be considered. Using a large-scale cohort from the Korean Longitudinal Study of Aging (KLoSA), we analyzed the combined effects of depression and chronic disease on all-cause mortality. @*Methods@#We analyzed 10-year (2006–2016) longitudinal data of 9,819 individuals who took part in the KLoSA, a nationwide survey of people aged 45–79 years. We examined the association between multimorbidity and depression using chi-square test and logistic regression. We used the Cox proportional hazard model to determine the combined effects of multimorbidity and depression on the all-cause mortality risk. @*Results@#During the 10-year follow up, 1,574 people (16.0%) died. The hazard ratio associated with mild depression increased from 1.35 (95% confidence interval [CI], 1.05–1.73) for no chronic disease to 1.25 (95% CI, 0.98–1.60) for 1 chronic disease, and to 2.00 (95% CI, 1.58–2.52) for multimorbidity. The hazard ratio associated with severe depression increased from 1.73 (95% CI, 1.33–2.24) for no chronic disease, to 2.03 (95% CI, 1.60–2.57) for 1 chronic disease, and to 2.94 (95% CI, 2.37–3.65) for multimorbidity. @*Conclusion@#Patients with coexisting multimorbidity and depression are at an increased risk of all-cause mortality than those with chronic disease or depression alone.

Cancer Survivors with Low Hand Grip Strength Have Decreased Quality of Life Compared with Healthy Controls: The Korea National Health and Nutrition Examination Survey 2014–2017 / 가정의학회지

Background@#Cancer survivors experience decreased physical function and reduced muscle strength, which leads to lower quality of life (QOL). The hand grip strength (HGS) can be a predictor of poor health-related QOL as a parameter of sarcopenia. The purpose of this study was to investigate the relationship between low HGS and QOL in cancer survivors and healthy controls. @*Methods@#We analyzed 392 cancer survivors and 1,176 healthy controls from the Korea National Health and Nutrition Examination Survey, 2014–2017. We defined low HGS as 2 standard deviation values for healthy young Korean adults from a previous study. QOL was evaluated using the European Quality of Life Scale-Five Dimensions. A complex sample logistic regression model was used to assess the relationship between each dimension of low HGS and QOL. @*Results@#The odds ratios (ORs) for decreased QOL were significantly higher in male cancer survivors with low HGS on self-care (OR, 8.51; 95% confidence interval [CI], 1.69–42.83) and usual activities (OR, 6.63; 95% CI, 1.22–36.03). The ORs for problems in mobility (OR, 5.87; 95% CI, 2.04–16.91), usual activities (OR, 14.46; 95% CI, 3.84–54.44), pain/discomfort (OR, 4.90; 95% CI, 2.00–12.01), and anxiety/depression (OR, 6.43; 95% CI, 2.16–19.12) were significantly high in female cancer survivors with low HGS. However, healthy controls showed no significant relationship between low HGS and QOL. @*Conclusion@#For cancer survivors, low HGS was associated with poor QOL in some domains. Strategies to increase muscle strength must be considered to improve the QOL of cancer survivors.

Effect of Increasing Tobacco Prices on Stages of Smoking Cessation: A Korean Nationwide Data Analysis / 가정의학회지

Background@#In 2015, tobacco prices significantly increased in Korea as part of the government’s smoking cessation policy. This study examined the changes in the stages of smoking cessation among Korean male smokers before and after the implementation of the tobacco price policy, and identified the predictors of such changes. @*Methods@#The study population comprised 3,533 male current smokers (age ≥19 years) who participated in the Korea National Health and Nutrition Survey in 2012, 2013, 2015, and 2016. Current smokers were defined as persons who had smoked ≥100 cigarettes during their lifetime and are continuing to smoke. In accordance with the transtheoretical model, smokers were classified into the precontemplation stage (no plan to quit), contemplation stage, and preparation stage (planning to quit within 6 months). We examined the changes in the smoking cessation stages before and after the implementation of the policy. Multivariate logistic regression analysis was conducted to identify factors related to the likelihood of continuing smoking, after adjustments for potential confounders. @*Results@#Immediately after the policy implementation, the percentage of smokers in the precontemplation stage decreased from 65.6% to 60.8% (P=0.014). However, this effect was temporary. Significant risk factors for remaining in the precontemplation stage were older age (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.002–1.018; P=0.004), being in the lowest income quartile (OR, 1.226; 95% CI, 1.001–1.502; P=0.049), and manual worker or unemployed status (OR, 1.256; 95% CI, 1.036–1523; P=0.020). @*Conclusion@#Increasing tobacco prices only temporarily change the stage of smoking cessation among Korean male smokers.

Combined Effects of Depression and Chronic Disease on the Risk of Mortality: The Korean Longitudinal Study of Aging (2006-2016)

Background@#The prevalence of depression is much higher in people with chronic disease than in the general population. Depression exacerbates existing physical conditions, resulting in a higher-than-expected death rate from the physical condition itself. In our aging society, the prevalence of multimorbid patients is expected to increase; the resulting mental problems, especially depression, should be considered. Using a large-scale cohort from the Korean Longitudinal Study of Aging (KLoSA), we analyzed the combined effects of depression and chronic disease on all-cause mortality. @*Methods@#We analyzed 10-year (2006–2016) longitudinal data of 9,819 individuals who took part in the KLoSA, a nationwide survey of people aged 45–79 years. We examined the association between multimorbidity and depression using chi-square test and logistic regression. We used the Cox proportional hazard model to determine the combined effects of multimorbidity and depression on the all-cause mortality risk. @*Results@#During the 10-year follow up, 1,574 people (16.0%) died. The hazard ratio associated with mild depression increased from 1.35 (95% confidence interval [CI], 1.05–1.73) for no chronic disease to 1.25 (95% CI, 0.98–1.60) for 1 chronic disease, and to 2.00 (95% CI, 1.58–2.52) for multimorbidity. The hazard ratio associated with severe depression increased from 1.73 (95% CI, 1.33–2.24) for no chronic disease, to 2.03 (95% CI, 1.60–2.57) for 1 chronic disease, and to 2.94 (95% CI, 2.37–3.65) for multimorbidity. @*Conclusion@#Patients with coexisting multimorbidity and depression are at an increased risk of all-cause mortality than those with chronic disease or depression alone.

Low Doses of Baclofen Induced Nonconvulsive Status Epilepticus in a Patient with Chronic Kidney Disease

Baclofen, a gamma-aminobutyric acid B agonist, is frequently used in the treatment of various neurologic diseases including spasticity, dystonia and trigeminal neuralgia. This drug usually acts at the presynaptic motor neuron to induce an antispastic response. Oral baclofen toxicity is extremely rare, but is often reported to affect patients with renal disease. Here, we report a patient with chronic kidney disease who was treated with relatively low doses of baclofen (5 mg twice per day) and experienced nonconvulsive status epilepticus.

Liver X Receptor β Related to Tumor Progression and Ribosome Gene Expression in Papillary Thyroid Cancer

Background@#Intracellular lipid deposition has been reported in thyroid glands in obese animal and human. To understand the regulatory mechanism of lipid metabolism in thyroid cancer, we investigated the expression status of liver X receptor (LXR) and analyzed its clinicopathological characteristics and molecular biological features. @*Methods@#Expression status of LXR and its transcriptional targets in human cancers were analyzed using The Cancer Genome Atlas (TCGA). The gene-sets related to high LXRβ expression was investigated by gene set enrichment analysis (GSEA) using Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways and gene ontology biologic process. Quantitative reverse transcription polymerase chain reaction was performed in thyroid cancer samples using our validation cohort. @*Results@#In contrast to low expression of LXRα, LXRβ was highly expressed in thyroid cancer compared to the other types of human cancers. High LXRβ expression was correlated with the expression of LXRβ transcriptional targets genes, such as apolipoprotein C1 (APOC1), APOC2, apolipoprotein E (APOE), ATP binding cassette subfamily G member 8 (ABCG8), sterol regulatory elementbinding protein 1c (SREBP1c), and SPOT14. Furthermore, High LXRβ expression group indicated poor clinicopathological characteristics and aggressive molecular biological features independently from the drive mutation status. Mechanistically, high LXRβ expression was coordinately related to ribosome-related gene sets. @*Conclusion@#The mechanistic link between LXRβ and ribosomal activity will be addressed to develop new diagnostic and therapeutic targets in thyroid cancers.

Predicting Vascularized Bone Graft Viability Using 1-Week Postoperative Bone SPECT/CT After Maxillofacial Reconstructive Surgery / 대한핵의학회잡지

Purpose@#We aimed to evaluate the performance of hybrid bone single-photon emission computed tomography (SPECT)/computed tomography (CT) in predicting bone graft viability after maxillary or mandibular reconstructive surgery with vascularized bone grafts. @*Methods@#We retrospectively reviewed 46 bone planar scintigraphy and SPECT/CT images of 45 adult patients taken at 1 week (5–8 days) after maxillary or mandibular reconstructive surgery with vascularized bone grafts. By visual analysis, two nuclear medicine physicians scored the uptake degrees of each bone graft segment compared with the calvarium uptake on planar bone scintigraphy and SPECT/CT, respectively (0 = absence of uptake, 1 = less uptake, 2 = similar uptake, and 3 = more uptake). The imaging results were compared with clinical follow-up for assessing bone graft viability. @*Results@#During follow-up, five bone graft segments were surgically removed and confirmed as nonviable—one had a score of 0, although the other four had a score of 1–3 on planar bone scintigraphy. All five bone graft segments were scored 0 on SPECT/CT and eventually confirmed as nonviable. All other graft segments with a score of > 1 on SPECT/CT were viable and uneventful.The anatomical CT information on SPECT/CT images was helpful in discriminating bone graft uptake from adjacent bone or soft tissue uptake. @*Conclusions@#The absence of tracer uptake by the vascularized bone graft on bone SPECT/CT at 1 week after maxillary or mandibular reconstructive surgery can predict graft failure. Bone SPECT/CT can be used to predict vascularized bone graft viability postoperatively.

Age-Specific Cutoffs of the Sysmex UF-1000i Automated Urine Analyzer for Rapid Screening of Urinary Tract Infections in Outpatients

We investigated the usefulness of age-specific cutoffs for screening of urinary tract infections (UTIs) in Korean outpatients, using the automated urine analyzer UF-1000i (Sysmex, Kobe, Japan). We retrospectively reviewed outpatient medical records. Urine samples of 7,443 outpatients from January 2010 to December 2017 were analyzed using urine culture and UF-1000i. ROC curves were calculated for each UF-1000i parameter based on the culture results. There were 1,398 culture positive samples, 5,774 culture negative samples, and 271 contaminated samples. UF-1000i had an area under the curve of ≥0.9 in outpatients >15 years. The appropriate cutoffs, which are the sum of bacterial (B-A-C) and white blood cell (WBC) counts, were 297.10/µL (15–24 years), 395.65/µL (25–44 years), 135.65/µL (45–64 years), 67.95/µL (65–74 years), and 96.5/µL (≥75 years). B-A-C and WBC counts differed among the three most frequently identified bacteria (Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis). The UF-1000i system is useful for applying age-specific cutoffs to screen for UTIs, thereby preventing antibiotic abuse and reducing antibiotic resistance. Future studies can explore how its B-A-C and WBC counts can facilitate selection of empirical antibiotics by distinguishing between gram-positive and gram-negative bacteria.

False-negative Hepatobiliary Scintigraphy for Biliary Atresia / 대한핵의학회잡지

We present the case of a patient with biliary and duodenal atresia who showed false-negative hepatobiliary scintigraphy results. The patient was born at 37 weeks and 2 days of gestation. Her mother had undergone amnioreduction after detection of a double-bubble ultrasound sign in the fetal abdomen. At 2 days of age, total serum bilirubin level was elevated. On hepatobiliary scintigraphy 4 days later, the gallbladder was visualized from 30 min and it showed duodeno-gastric reflux at 240 min. After 24 h, the radiotracer was almost washed out in the hepatic parenchyma, but there was retention in the gastroduodenal junction. Because the biliary to duodenal transit was visible, biliary atresia seemed unlikely. Abdominal ultrasonography at 7 days of age showed a small dysmorphic gallbladder, but triangular cord sign was not definite. Magnetic resonance cholangiography revealed atretic gallbladder. Although cystic and common bile ducts were visible, the proximal common hepatic bile duct was not visible. The next day, serum total bilirubin levels remained elevated (17.1 mg/dl) with direct bilirubin level of 1.2 mg/dl. Kasai portoenterostomy with duodeno-duodenostomy was performed at 10 days of age. Histopathological evaluation showed a fibrous obliteration of the common bile duct, consistent with that of biliary atresia.

False-negative Hepatobiliary Scintigraphy for Biliary Atresia / 대한핵의학회잡지

We present the case of a patient with biliary and duodenal atresia who showed false-negative hepatobiliary scintigraphy results. The patient was born at 37 weeks and 2 days of gestation. Her mother had undergone amnioreduction after detection of a double-bubble ultrasound sign in the fetal abdomen. At 2 days of age, total serum bilirubin level was elevated. On hepatobiliary scintigraphy 4 days later, the gallbladder was visualized from 30 min and it showed duodeno-gastric reflux at 240 min. After 24 h, the radiotracer was almost washed out in the hepatic parenchyma, but there was retention in the gastroduodenal junction. Because the biliary to duodenal transit was visible, biliary atresia seemed unlikely. Abdominal ultrasonography at 7 days of age showed a small dysmorphic gallbladder, but triangular cord sign was not definite. Magnetic resonance cholangiography revealed atretic gallbladder. Although cystic and common bile ducts were visible, the proximal common hepatic bile duct was not visible. The next day, serum total bilirubin levels remained elevated (17.1 mg/dl) with direct bilirubin level of 1.2 mg/dl. Kasai portoenterostomy with duodeno-duodenostomy was performed at 10 days of age. Histopathological evaluation showed a fibrous obliteration of the common bile duct, consistent with that of biliary atresia.

Low Dose Exposure to Di-2-Ethylhexylphthalate in Juvenile Rats Alters the Expression of Genes Related with Thyroid Hormone Regulation

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

Successful Localization Using ⁶⁸Ga-DOTATOC PET/CT of a Phosphaturic Mesenchymal Tumor Causing Osteomalacia in a Patient with Concurrent Follicular Lymphoma / 대한핵의학회잡지

Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of ⁶⁸Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body ¹⁸F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. ⁶⁸Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient's serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.

Successful Localization Using ⁶⁸Ga-DOTATOC PET/CT of a Phosphaturic Mesenchymal Tumor Causing Osteomalacia in a Patient with Concurrent Follicular Lymphoma / 대한핵의학회잡지

Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of ⁶⁸Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body ¹⁸F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. ⁶⁸Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient's serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.