Vascular Uptake on 18 F-FDG PET/CT During the Clinically Inactive State of Takayasu Arteritis Is Associated with a Higher Risk of Relapse

Purpose: To evaluate whether vascular uptake on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) during the clinically inactive state of Takayasu arteritis (TAK) is associated with disease relapse. Materials and methods: Patients with TAK who underwent 18F-FDG PET/CT during the clinically inactive state of the disease between 2006 and 2019 were included. Clinically inactive disease was defined as a status not fulfilling the National Institutes of Health (NIH) criteria for active disease in TAK. Relapse was defined as recurrence of clinically active disease after a clinically inactive period, requiring change in the treatment regimen. Vascular uptake on 18F-FDG PET/CT was assessed using target/background ratio (TBR), calculated as arterial maximum standardized uptake value (SUV)/mean SUV in venous blood pool. Multivariable Cox regression analysis was performed to identify factors associated with relapse. Results: A total of 33 patients with clinically inactive TAK were included. During a median observation period of 4.5 (0.9-8.1) years, relapse occurred in 9 (27.3%) patients at median 1.3 (0.7-6.9) years. Notably, TBR [1.5 (1.3-1.8) vs. 1.3 (1.1-1.4), p=0.044] was significantly higher in patients who relapsed than in those who did not. On multivariable Cox regression analysis, the presence of NIH criterion 2 [adjusted hazard ratio (HR): 7.044 (1.424-34.855), p=0.017] and TBR [adjusted HR: 11.533 (1.053-126.282), p=0.045] were significantly associated with an increased risk of relapse. Conclusion: Vascular uptake on 18F-FDG PET/CT and the presence of NIH criterion 2 are associated with future relapse in patients with clinically inactive TAK.ope

담도암 줄기 세포의 분자표지자로서 가능성 있는 CD151

Dept. of Medicine/박사Cancer stem cells are currently hypothesized to be responsible for tumorigenesis, metastasis, recurrence, and chemoresistance in the various types of cancer. CD151 is a member of the transmembrane 4 superfamily, which enhances cell motility, invasion, and metastasis of cancer cells. In intrahepatic cholangiocarcinoma, overexpression of CD151 associated with c-Met is implicated in invasion and metastasis, which result in poor prognosis. However, there are few studies that focus on CD151 in cholangiocarcinoma, and the role of CD151 in cancer stem cells, including cholangiocarcinoma stem cells, which have hardly been documented. The aim of this study is therefore to characterize the role of CD151 in cholangiocarcinoma stem cell. To evaluate cholangiocarcinoma stem cell, the author prepared cancer stem like cells using sphere cultivation (SNU-245, SNU-1196). A cDNA microarray was used to gain up-regulated genes between tumorsphere and biliary carcinoma. The expressions of stemness genes and the proteins related to c-Met and Epithelial Mesenchymal Transition (EMT) were evaluated through RT-PCR and western blot to find if tumorsphere has characteristics of stem cell. Expression of CD151 was compared between adherent cells of SNU-1196 and tumorsphere. To evaluate the role of CD151 in cholangiocarcinoma stem cells, CD151 knockdown was done by CD151 siRNA in SNU-1196 cells and then sphere formation and cytotoxicity assay were performed. In order to evaluate the mechanism of CD151, c-Met, EMT pathway related molecules, β-catenin, and Oct 4 were evaluated through western blot. Proliferation and metastatic capabilities were also evaluated after transfection of CD151 siRNA in SNU-1196. As a result, CD151 gene was highly up-regulated in both tumorspheres and biliary carcinoma on cDNA microarray. Cultivated tumorsphere had cancer stem cell-like properties, showing highly expressed Notch, Hedgehog, and Wnt pathway related to stem cells in RT-PCR. Expressions of the proteins that related to c-Met, PI3K, EMT pathway, β-catenin, and Oct 4 were more highly increased and CD151 was more highly expressed in tumorsphere than in adherent cells. After CD151 knockdown, tumorsphere formation was inhibited and chemoresistance was reduced. The expression of the molecules associated c-Met, PI3K, EMT pathways, β-catenin and Oct4 was reduced. Therefore, the characteristics of proliferation and migration were also reduced after transfection of CD151 siRNA in SNU-1196 cells. The author could suggest that CD151 was more expressed in cholangiocarcinoma stem-like cells and regulated self-renewal, chemoresistance, proliferation and metastatic capabilities. It might interact with c-Met and activate PI3K, EMT pathway, β-catenin, and Oct4. So, it would be a potential cholangiocarcinoma stem cell related marker and therapeutic target in the future. 최근 암줄기 세포가 다양한 암에서 종양형성, 전이, 재발, 항암제내성을 일으킨다고 가정하고 있다. CD151은 transmembrane 4 superfamily의 하나로 세포의 이동뿐 아니라 암세포의 침습이나 전이에 관여한다. 간내 담도암에서 CD151과 c-Met의 과발현이 암의 침습과 전이와 연관이 있어 불량 예후를 보인다는 연구와 같이 담도암에서 CD151의 역할에 대한 연구는 있었으나 담도암 줄기세포에서의 역할에 대한 연구는 현재 없다. 이에 본 연구에서는 CD151의 담도암 줄기세포에서 역할을 대해서 알아보고자 하였다. 담도암 줄기세포에 대한 평가를 위해 본 연구에서는 2개의 담도암 세포주(SNU-245, SNU-1196)를 이용하여 tumorsphere를 배양하여 담도암 줄기 양 세포를 얻었다. cDNA microarray를 이용하여 tumorsphere와 담도암에서 과발현된 유전자를 얻었다. Tumorsphere가 줄기세포의 특성을 갖는 지를 보기 위해 RT-PCR과 western blot을 통하여 줄기세포 관련 mRNA와 c-Met과 EMT 관련 단백질을 확인하였다. CD151의 발현을 SNU-1196 세포주의 부착 세포와 tumorsphere에서 비교하였다. CD151의 담도암 줄기 세포에서의 역할을 확인하기 위하여 SNU-1196을 CD151 siRNA로 처리하여 CD151 발현을 억제한 후에 sphere formation assay, cytotoxicity assay를 시행하였다. 또한 c-Met, EMT pathway 관련 인자 및 β-catenin, Oct4의 발현을 western blot을 통하여 확인하였으며 proliferation assay 및 migration assay를 시행하였다. 결과적으로 cDNA microarray에서 CD151이 tumorsphere와 담도암 모두에서 과발현됨을 알 수 있었다. 배양된 tumor sphere는 RT-PCR에서 줄기세포와 관련된 Notch, Hedgehog, Wnt 관련 인자들이 과발현되고 있고, western blot에서 c-Met, PI3K, EMT 관련 인자, β-catenin, Oct4의 발현이 증가되어 있어서 암줄기 세포의 특성을 가지고 있었다. CD151은 부착 세포보다 tumors...ope

Fracture Healing Effects of Locally-Administered Adipose Tissue-Derived Cells

PURPOSE: Although the applications of adipose tissue-derived cells (ADCs) in regenerative medicine have been investigated, the role of ADCs in fracture healing remains unclear. In this study, we examined the fracture-healing effects and survival of transplanted ADCs using micro-computed tomography (CT) and bioluminescence imaging (BLI). MATERIALS AND METHODS: Luciferase-expressing ADCs were suspended in solubilized basement membrane preparation (SBMP) and xenografted on defects in the right femur of nude mice (n=5). SBMP alone was grafted on a defect in the contralateral femur. Serial in vivo micro-CT and BLI were performed for 20 days. Ex vivo BLI images of both femurs were obtained. Differences in the Hounsfield unit (HU), HU(ratio), and luciferase activities were compared using Wilcoxon signed-rank tests and non-parametric longitudinal analyses (p<0.05). RESULTS: In vivo BLI revealed a signal drop on day 2, reconstitution on day 5, and continuous decrement thereafter. Ex vivo BLI revealed residual activity in the ADC-implanted and adjacent areas. No activity was detected in the contralateral femur. The overall increment rate of normalized HUs was higher for ADC-treated femurs than for SBMP-treated femurs. Cell migration to distant injury sites was not detected.ope

The 18F-FDG PET/CT response to radiotherapy for patients with spinal metastasis correlated with the clinical outcomes

PURPOSE: To evaluate the potential role of 18F-fluorodeoxyglucose-positron emission tomography/computerized tomography (FDG-PET/CT) for predicting treatment response after radiotherapy (RT) in patients with spinal metastases. MATERIALS AND METHODS: A retrospective analysis was performed of 42 patients with spinal metastases who received RT from January 2010 to December 2014. All patients underwent FDG-PET/CT before and after treatment. Changes in metabolic responses, expressed as the maximum, mean, peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were analyzed to determine their association with clinical outcomes. RESULTS: The median age at the time of spinal metastasis diagnosis was 58 years. Median progression-free survival (PFS) and overall survival after RT were 15 months and 22.4 months, respectively. RT produced a significant decrease in SUVmean (2.27 to 1.41), SUVmax (6.87 to 2.99), SUVpeak (5.75 to 2.33) and TLG (52.84 to 24.17) when compared with the baseline values (p70% reduction in maximum SUV after treatment was independently associated with good PFS (p = 0.036). CONCLUSIONS: RT is an effective treatment for patients with spinal metastases, and there were significant changes in PET parameters compared with baseline. The metabolic response measured by SUV and TLG changes in FDG-PET/CT correlated with the clinical outcomes, especially with shorter PFS in patients who had higher residual maximum SUV after treatment.ope

Clinical practice guidelines for gastric cancer in Korea: An evidence-based approach

Although gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to those in western countries. However, there are currently no Korean multidisciplinary guidelines for gastric cancer. Experts from related societies developed guidelines de novo to meet Korean circumstances and requirements, including 23 recommendation statements for diagnosis (n=9) and treatment (n=14) based on relevant key questions. The quality of the evidence was rated according to the GRADE evidence evaluation framework: the evidence levels were based on a systematic review of the literature, and the recommendation grades were classified as either strong or weak. The applicability of the guidelines was considered to meet patients’ view and preferences in the context of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy, endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic evaluation. An external review of the guidelines was conducted during the finalization phase.ope

An extragastrointestinal stromal tumor in the omentum with peritoneal seeding mimicking an appendiceal mucinous cancer with carcinomatosis

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors tend to present most frequently in the stomach, followed by the small intestine. GISTs can also arise from the omentum, retroperitoneum, mesentery, or pleura and are termed extragastrointestinal stromal tumors (EGISTs) when they do so. EGISTs arising from the omentum are very rare. Due to the limited incidence of EGISTs in the omentum, the diagnostic criteria are not well established, and making a correct diagnosis may be difficult. In this report, we present a case of an EGIST of the omentum with peritoneal metastasis that was initially suspected to be an appendiceal mucinous carcinoma with carcinomatosis on positron emission tomography/computed tomography imaging.ope

Multiple Myeloma Mimics Bone Metastasis From a Rectal Adenocarcinoma

A presumptive diagnosis of bone metastasis can be easily made when a patient with a history of colorectal cancer develops bone lesions that are seen on follow-up imaging. In this case report, we describe a patient whose multiple bone lesions were wrongly attributed to a recurrence of rectal cancer rather than being identified as multiple myeloma lesions. When clinicians detect new, abnormal, bony lesions in a patient with a previous history of cancer, they should consider diseases such as multiple myeloma in their differential diagnosis.ope

Use of F-18-sodium fluoride bone PET for disability evaluation in ankle trauma: a pilot study

BACKGROUND: There are no objective and accurate rating tools for permanent impairment of traumatized ankles. The purpose of this study is to assess the role of 18F-Sodium fluoride (18F-NaF) positron emission tomography-computed tomography (PET/CT) bone scans in evaluating patients with limited ankle range of motion (ROM) after trauma. METHODS: 18F-NaF PET/CT was performed in 121 patients (75 men, 46 women; mean age: 45.8) who had ROM  2.5 was automatically obtained from the 3D volume that included the ankle joint. The maximum & mean SUV (SUVmax & SUVmean), and the total lesion activity (TLA) were measured. RESULTS: The median period from injury to performing 18F-NaF PET/CT was 290 days. The causes of injury were as follows: fracture (N = 95), Achilles tendon rupture (N = 12), and ligament injury (N = 12). Hot uptake in the ankle was seen in 113 of 121 patients. The fracture group had higher SUVmax, SUVmean, and TLA values than the non-fracture group. More limited ROM correlated with higher hot-uptake parameters (SUVmax, SUVmean, TLA). In subgroup analysis, the same correlations were present in the fracture, but not in the non-fracture group. CONCLUSIONS: 18F-NaF PET/CT can provide considerable information in impairment evaluations of limited ankle ROM, particularly in fracture around the ankle. Thus, 18F-NaF bone PET/CT may provide an additional option as an objective imaging tool in disability assessment after ankle injury.ope

Huge Pulmonary Sclerosing Pneumocytoma with Endobronchial Invasion: A Case Report with a Literature Review

Pulmonary sclerosing pneumocytoma (PSP) is a tumor of pneumocytic origin that is classified as a benign neoplasm. To date, aggressive behavior of this tumor has rarely been reported. Here, we describe a case of a 56-year-old woman with a huge, 19-cm PSP that resulted in mediastinal shift and showed microscopic endobronchial invasion and necrosis. The differential diagnosis included malignant mesenchymal tumors, such as solitary fibrous tumor; however, PSP was confirmed based on the characteristic thyroid transcription factor 1 positivity and membranous expression of Ki-67 on immunohistochemical staining of tumor cells.ope

[18F]-Fluorodeoxyglucose Positron Emission Tomography Can Contribute to Discriminate Patients with Poor Prognosis in Hormone Receptor-Positive Breast Cancer.

BACKGROUND: Patients with hormone receptor-positive breast cancer typically show favorable survival. However, identifying individuals at high risk of recurrence among these patients is a crucial issue. We tested the hypothesis that [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans can help predict prognosis in patients with hormone receptor-positive breast cancer. METHODS: Between April 2004 and December 2008, 305 patients with hormone receptor-positive breast cancer who underwent FGD-PET were enrolled. Patients with luminal B subtype were identified by positivity for human epidermal growth factor receptor-2 (HER2) or high Ki67 (≥14%) according to criteria recently recommended by the St. Gallen panelists. The cut-off value of SUVmax was defined using the time-dependent receiver operator characteristic curve for recurrence-free survival (RFS). RESULTS: At a median follow up of 6.23 years, continuous SUVmax was a significant prognostic factor with a hazard ratio (HR) of 1.21 (p = 0.021). The cut-off value of SUVmax was defined as 4. Patients with luminal B subtype (n = 82) or high SUVmax (n = 107) showed a reduced RFS (p = 0.031 and 0.002, respectively). In multivariate analysis for RFS, SUVmax carried independent prognostic significance (p = 0.012) whereas classification with immunohistochemical markers did not (p = 0.274). The Harell c-index was 0.729. High SUVmax was significantly associated with larger tumor size, positive nodes, HER2 positivity, high Ki67 (≥14%), high tumor grade, and luminal B subtype. CONCLUSIONS: Among patients with hormone receptor-positive breast cancer, FDG-PET can help discriminate patients at high risk of tumor relapse.ope