1.Clinical examination: losing the shine.
Pankaj Kumar GARG ; Anjay KUMAR
Singapore medical journal 2012;53(2):149-149
2.Early evaluation for treatment efficacy of 5-fluorouracil and hyperthermia on HCT-116 colon cancer cells by fluorine-18-fluorodeoxyglucose uptake.
Zhen-xin WANG ; Bin ZHANG ; Sheng-ming DENG ; Shao-ji CHEN
Chinese Medical Journal 2012;125(4):657-661
BACKGROUNDFluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography imaging can be used to assess the treatment efficacy of chemotherapy and prognosis. The aim of this study was to determine the uptake rate of (18)F-FDG in colon cancer HCT-116 cells, and to evaluate the treatment efficacy of chemotherapy, hyperthermia and thermo-chemotherapy through the uptake inhibition rate of (18)F-FDG.
METHODSThe uptake rate of (18)F-FDG in HCT-116 cells was determined at various experimental conditions. The inhibition rate of cell growth, uptake rate of (18)F-FDG and uptake inhibition rate of (18)F-FDG in HCT-116 cells treated with 5-fluorouracil (5-FU) at various concentrations were determined. In HCT-116 cells subjected to chemotherapy (5-FU, 100 µg/ml), hyperthermia (43°C, 40 minutes) and thermo-chemotherapy for 24 hours, the inhibition rate of cell growth and uptake inhibition rate of (18)F-FDG were determined; early apoptosis, the morphology and ultrastructure of HCT-116 cells were examined; and the contents of glucose and lactate dehydrogenase (LDH) in the cell culture medium of HCT-116 cells were determined. One-way analysis of variance (ANOVA) and correlation analyses were conducted by using SPSS 16.0 software.
RESULTSThe uptake rate of (18)F-FDG in HCT-116 cells was (44.25 ± 2.19)%. Under the condition of adding 5-FU at various concentrations for 24 hours, the uptake rate of (18)F-FDG was negatively correlated with 5-FU dosage (r = -0.879, P < 0.01); the inhibition rate of cell growth revealed a positive correlation with the uptake inhibition rate of (18)F-FDG (r = 0.831, P < 0.01). In HCT-116 cells subjected to hyperthermia, chemotherapy, and thermo-chemotherapy for 24 hours, the uptake inhibition rates of (18)F-FDG were (12.94 ± 2.80)%, (28.25 ± 4.59)%, and (21.60 ± 3.68)%, respectively. The early apoptotic rates of HCT-116 cells were (9.80 ± 0.16)%, (19.80 ± 2.40)%, and (15.70 ± 1.80)%, respectively. Moreover, the contents of glucose and LDH in cell culture medium of HCT-116 cells after treatments were higher than those before treatment.
CONCLUSIONThe uptake inhibition rate of (18)F-FDG can be used for early evaluation of hyperthermia and 5-FU treatment efficacy on cancer cells although hyperthermia (43°C, 40 minutes) does not reveal the synergistic effect on 5-FU at the low dosage.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; metabolism ; Fever ; metabolism ; Fluorodeoxyglucose F18 ; metabolism ; Fluorouracil ; pharmacology ; HCT116 Cells ; Humans ; Microscopy, Electron, Transmission
3.IL-10 suppresses inflammatory granuloma uptake of 18F-FDG in rats.
Jianjun HE ; Qianchun YE ; Ke ZHI
Journal of Central South University(Medical Sciences) 2012;37(7):748-751
OBJECTIVE:
To evaluate the effectiveness of IL-10 in suppressing 18F-FDG uptake in the inflammatory granuloma of SD rats.
METHODS:
Eight SD rats were killed, and their blood was collected sterily. After centrifugion, the white blood cells were incubated in PRMI 1640 for 3 days. Then each culture flask of white blood cells was divided into two equal parts. To one group was added 0.2 mL IL-10 solution (0.1 mg/mL); to the control was added with 0.2 mL of 0.9% sodium chloride solution. All cells were then incubated for 120 minutes at 37 degree, after which 18F-FDG (1.85 MBq) was added. Sixty minutes later, the cells were washed twice with PBS and the extent of uptake 18F-FDG determined. In vivo, an inflammatory granuloma was produced by hypodermic injection of rats with a mixture of Freund's complete adjuvant, bovine serum albumin and talcum powder. Each rat was maintained for 8 weeks. Imaging of the inflammatory granulomas was performed using the 18F-FDG signal. IL-10 was injected into SD rats at 10 μg/kg of body weight. Sixty minutes later, 7.4 MBq of 18F-FDG were injected, and, after a further 60 minutes, the rats underwent a PET-CT scan. The region of interest (ROI) of the inflammatory granuloma was delineated and the standard uptake value (SUV) calculated. A second PET-CT scan was done without IL-10 on the next day. The granulomatous tissue underwent pathological examination.
RESULTS:
In the intro test, the with blood cell uptaking ratio of 18F-FDG was (50.3±6.7)% without IL-10, and (34.6±3.5)% with IL-10(t=8.9, P<0.01). IL-10 suppressed the rat white blood cell uptaking 18F-FDG. In the PET-CT scan, the SUV of ROI on inflammatory granuloma was 1.7±0.4 with IL-10 and 2.1±0.3 without IL-10 (t=20.6, P<0.01). IL-10 suppressed the inflammatory granuloma uptaking 18F-FDG.
CONCLUSION
IL-10 can suppress the inflammatory granuloma of SD rats uptaking 18F-FDG.
Animals
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Female
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Fluorodeoxyglucose F18
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pharmacokinetics
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Freund's Adjuvant
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Granuloma
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chemically induced
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metabolism
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Interleukin-10
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pharmacology
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Lung Diseases
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chemically induced
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metabolism
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Male
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Radiopharmaceuticals
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pharmacokinetics
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Rats
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Serum Albumin, Bovine
4.FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model.
Hee Sun PARK ; Jin Wook CHUNG ; Hwan Jun JAE ; Young Il KIM ; Kyu Ri SON ; Min Jong LEE ; Jae Hyung PARK ; Won Jun KANG ; Jung Hwan YOON ; Hesson CHUNG ; Kichang LEE
Korean Journal of Radiology 2007;8(3):216-224
OBJECTIVE: We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. RESULTS: The SUV of the VX2 tumors before treatment (3.87+/-1.51[mean+/-SD]) was significantly higher than that of nontumorous liver parenchyma (1.72+/-0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05+/-1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41+/-0.73) than that before treatment (p = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48%+/-15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. CONCLUSION: Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.
Animals
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Disease Models, Animal
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Enzyme Inhibitors/*pharmacology
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Feasibility Studies
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Fluorodeoxyglucose F18
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Infusions, Intra-Arterial
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Injections, Intra-Arterial
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Liver Neoplasms, Experimental/*drug therapy/pathology/*radionuclide imaging
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Necrosis
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*Positron-Emission Tomography
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Pyruvate Dehydrogenase Complex/antagonists & inhibitors
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Pyruvates/*pharmacology
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Rabbits
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Radiopharmaceuticals
5.Differences in Regional Glucose Metabolism of the Brain Measured with F-18-FDG-PET in Patients with Essential Tremor According to Their Response to Beta-Blockers.
In Uk SONG ; Sang Won HA ; Young Soon YANG ; Yong An CHUNG
Korean Journal of Radiology 2015;16(5):967-972
OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.
Adrenergic beta-Antagonists/*pharmacology/therapeutic use
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Aged
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Brain/*drug effects/metabolism/radiography
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Brain Mapping
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Essential Tremor/*diagnosis/drug therapy/radiography
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Fluorodeoxyglucose F18/*chemistry
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Glucose/*metabolism
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Humans
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Male
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Middle Aged
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*Positron-Emission Tomography
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Propranolol/pharmacology/therapeutic use
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Radiopharmaceuticals/*chemistry
6.Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.
Da Un JEONG ; Jin Hwan OH ; Ji Eun LEE ; Jihyeon LEE ; Zang Hee CHO ; Jin Woo CHANG ; Won Seok CHANG
Yonsei Medical Journal 2016;57(1):165-172
PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.
Acetylcholine/metabolism
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Alzheimer Disease
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Animals
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Antibodies, Monoclonal/*pharmacology
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Basal Forebrain/*drug effects/metabolism
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Cholinergic Agents/administration & dosage/*pharmacology
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Cholinergic Neurons/*drug effects/metabolism
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Fluorodeoxyglucose F18
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GABAergic Neurons/*drug effects/metabolism
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Glucose/*metabolism
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Gyrus Cinguli/*drug effects/metabolism
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Humans
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Injections
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Maze Learning
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Motor Activity/physiology
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Positron-Emission Tomography
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Rats
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Ribosome Inactivating Proteins, Type 1/*pharmacology
7.Recent Chemotherapy Reduces the Maximum-Standardized Uptake Value of 18F-Fluoro-Deoxyglucose Positron Emission Tomography in Colorectal Cancer.
Minjong LEE ; Tae Sung YEUM ; Ji Won KIM ; Sohee OH ; Shin Ae LEE ; Hong Ran MOON ; Young Hoon CHOI ; Yoo Min HAN ; Ji Min CHOI ; Dong Kee JANG
Gut and Liver 2014;8(3):254-264
BACKGROUND/AIMS: The aim of this study was to evaluate the influence of recent chemotherapy on the patterns of the maximum-standardized uptake value (M-SUV) and sensitivity of 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in colorectal cancer. METHODS: We retrospectively analyzed the FDG-PET/CT of 509 patients who underwent surgery for colorectal cancer. Subgroup analysis was performed according to chemotherapy status; 401 patients were not treated with chemotherapy and 108 patients were treated with chemotherapy within 6 months prior to surgery. Pathologic analysis of the surgical specimen was used as the gold standard. RESULTS: The M-SUV was significantly lower in patients treated with chemotherapy than in those not treated with chemotherapy in pathologically confirmed same stages of disease. The difference in the sensitivity of the M-SUV according to chemotherapy status was greatest using a cutoff M-SUV value of 6.4 (p<0.001). The longest diameter of the primary tumor was the most important factor that correlated with M-SUV of the primary tumor irrespective of the chemotherapy effect (p<0.001). The M-SUV of the primary tumor was not an independent predictor of lymph node metastasis in colorectal cancer. CONCLUSIONS: The results indicate that the M-SUV of FDG-PET/CT should be interpreted in the context of concurrent chemotherapy.
Aged
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Antineoplastic Agents/*adverse effects
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Chemoradiotherapy, Adjuvant/adverse effects
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Chemotherapy, Adjuvant/adverse effects
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Colorectal Neoplasms/drug therapy/pathology/*radionuclide imaging
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Female
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Fluorodeoxyglucose F18/diagnostic use/*pharmacology
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Humans
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Male
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Positron-Emission Tomography/methods
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Radiopharmaceuticals/diagnostic use/*pharmacology
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Retrospective Studies
8.Suppressive Effect of 19-nor-1alpha-25-Dihydroxyvitamin D2 on Gastric Cancer Cells and Peritoneal Metastasis Model.
Mi Ra PARK ; Ji Hee LEE ; Myung Suk PARK ; Jun Eul HWANG ; Hyun Jeong SHIM ; Sang Hee CHO ; Ik Joo CHUNG ; Woo Kyun BAE
Journal of Korean Medical Science 2012;27(9):1037-1043
The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), inhibits the growth of several types of human cancer cells in vitro, but its therapeutic use is limited because it causes hypercalcemia. Among its analogs, 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol), has fewer calcemic effects and exhibits an activity equipotent to that of calcitriol. We assessed the antitumor and anti-inflammatory effects of paricalcitol in gastric cancer cells, and evaluated the potential role of vitamin D in the treatment of peritoneal metastatic gastric cancer. In this study, treatment with paricalcitol inhibited gastric cancer cell growth and induced cell cycle arrest. Paricalcitol also induced apoptosis and showed anti-inflammatory activity. Moreover, the growth of intraperitoneal metastases in vivo was reduced in mice treated with paricalcitol. 18F-FDG uptake was significantly lower in the paricalcitol group compared to control group (SUV; control group 13.2 +/- 5.3 vs paricalcitol group 4.5 +/- 3.0). Intraperitoneal tumor volume was significantly lower in paricalcitol treated mice (control group 353.2 +/- 22.9 mm3 vs paricalcitol group 252.0 +/- 8.4 mm3). These results suggest that the vitamin D analog, paricalcitol, has anticancer activity on gastric cancer cells by regulation of the cell cycle, apoptosis, and inflammation.
Animals
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Antineoplastic Agents/chemistry/*pharmacology/therapeutic use
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Apoptosis/drug effects
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Cell Cycle Checkpoints/drug effects
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Cell Cycle Proteins/metabolism
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Cell Line, Tumor
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Cell Proliferation/drug effects
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Disease Models, Animal
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Ergocalciferols/chemistry/*pharmacology/therapeutic use
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Fluorodeoxyglucose F18/chemistry/diagnostic use
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Humans
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Mice
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Mice, Inbred BALB C
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Peritoneal Neoplasms/drug therapy/*secondary
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Positron-Emission Tomography
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Stomach Neoplasms/drug therapy/*pathology
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Transplantation, Heterologous
9.Circumferential Resection Margin Involvement in Stage III Rectal Cancer Patients Treated with Curative Resection Followed by Chemoradiotherapy: A Surrogate Marker for Local Recurrence?.
Jeonghyun KANG ; Hyunki KIM ; Hyuk HUR ; Byung Soh MIN ; Seung Hyuk BAIK ; Kang Young LEE ; Seung Kook SOHN ; Nam Kyu KIM
Yonsei Medical Journal 2013;54(1):131-138
PURPOSE: Circumferential resection margin (CRM) involvement is a well-known predictor for poor prognosis in rectal cancer. However, the significance is controversial in some studies. Accordingly, this study attempted to examine the prognostic impact of CRM involvement in stage III rectal cancer. MATERIALS AND METHODS: Between January 1990 and December 2007, a total of 449 patients who underwent curative resection followed by complete adjuvant chemoradiotherapy for stage III rectal cancer located within 12 cm from the anal verge were selected. Patients were divided into a CRM-positive group (n=79, 17.6%) and a CRM-negative group (n=370, 82.4%). RESULTS: With a median follow-up of 56.6 months, recurrent disease was seen in 53.2 and 43.5% of the CRM-positive and CRM-negative group, respectively. CRM involvement was an independent prognostic factor for 5-year systemic recurrence-free survival (HR: 1.5, CI: 1.0-2.2, p=0.017). However, no significant difference was observed for local recurrence rate between the two groups (13.0 and 13.5%, respectively, p=0.677). CONCLUSION: In this study, local recurrence rate did not differ according to CRM involvement status in stage III rectal cancer patients, although CRM involvement was shown to be an independent poor prognostic factor. Accordingly, validation of the results of this study by further large prospective randomized trials is warranted.
Aged
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Biological Markers
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Chemoradiotherapy/*methods
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Female
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Fluorodeoxyglucose F18/pharmacology
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Follow-Up Studies
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Humans
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Lymphatic Metastasis
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Magnetic Resonance Imaging
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Male
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Middle Aged
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Neoplasm Metastasis
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Neoplasm Recurrence, Local
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Neoplasm Staging
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Positron-Emission Tomography
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Prognosis
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Rectal Neoplasms/diagnosis/*surgery/*therapy
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Recurrence
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Surgical Procedures, Operative
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Tomography, X-Ray Computed
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Treatment Outcome