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Prognostic value of pretreatment 18F-FDG PET-CT in radiotherapy for patients with hepatocellular carcinoma

  • Jo, In Young;Son, Seok-Hyun;Kim, Myungsoo;Sung, Soo Yoon;Won, Yong Kyun;Kang, Hye Jin;Lee, So Jung;Chung, Yong-An;Oh, Jin Kyoung;Kay, Chul-Seung
    • Radiation Oncology Journal
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    • v.33 no.3
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    • pp.179-187
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    • 2015
  • Purpose: The purpose of this study was to investigate the predictable value of pretreatment $^{18}F$-fluorodeoxyglucose positron emission tomography-computed tomography ($^{18}F$-FDG PET-CT) in radiotherapy (RT) for patients with hepatocellular carcinoma (HCC) or portal vein tumor thrombosis (PVTT). Materials and Methods: We conducted a retrospective analysis of 36 stage I-IV HCC patients treated with RT. $^{18}F$-FDG PET-CT was performed before RT. Treatment target was determined HCC or PVTT lesions by treatment aim. They were irradiated at a median prescription dose of 50 Gy. The response was evaluated within 3 months after completion of RT using the Response Evaluation Criteria in Solid Tumors (RECIST). Response rate, overall survival (OS), and the pattern of failure (POF) were analyzed. Results: The response rate was 61.1%. The statistically significant prognostic factor affecting response in RT field was maximal standardized uptake value (maxSUV) only. The high SUV group (maxSUV ${\geq}5.1$) showed the better radiologic response than the low SUV group (maxSUV < 5.1). The median OS were 996.0 days in definitive group and 144.0 days in palliative group. Factors affecting OS were the %reduction of alpha-fetoprotein (AFP) level in the definitive group and Child-Pugh class in the palliative group. To predict the POF, maxSUV based on the cutoff value of 5.1 was the only significant factor in distant metastasis group. Conclusion: The results of this study suggest that the maxSUV of $^{18}F$-FDG PET-CT may be a prognostic factor for treatment outcome and the POF after RT. A %reduction of AFP level and Child-Pugh class could be used to predict OS in HCC.

Therapeutic Effect of Combined Radiotherapy and Hyperthermia in Primary Hepatocellular Carcinoma (원발성 간암의 방사선치료및 온열요법의 병용치료 효과)

  • Kang Ki Mun;Choi Ihl Bohng;Kay Chul Seung;Choi Byung Ok;Chung Su Mi;Kim In Ah;Han Sung Tae;Sun Hee Sik;Chung Kyu Won;Shinn Keyong Sub
    • Radiation Oncology Journal
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    • v.12 no.2
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    • pp.191-199
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    • 1994
  • Purpose : This study was undertaken to show the clinical results of combined radiotherapy and hyperthermia in primary hepatoma Materials and Methods : Between December 1989 and March 1993, 50 patients with hepatomas were treated by combined radiotherapy and hyperthermia. Among them, we analyzed retrospectively 33 patients who received the complete course of treatment. The ages of the patients ranged from 36 to 75(mean age: 55.5 years). Twenty-six patients ($78.8\%$) were men, and 7 ($21.2\%$ were women. According to Child's classification, nine patients ($27.3{\%}$) were A group, 9 ($27.3\%$) were B group, 15 ($45.4\%$) were C group. Radiation therapy was done by a 6 MV and 15 MV linear accelerator. Patients were treated with daily fractions of 150-180 cCy to doses of 2550 cGy -4950 cGy (median : 3000 cGy). Local hyperthermia was done by 8 MHZ RF capacitive heating device (Cancermia. Green Cross Co., Korea), 50-60 min/session, 1-2 sessions/wk, and 8.5 sessions (median number)/patient. We analyzed the prognostic factors including age, sex, tumor type, Child's classification, $\alpha$-fetoprotein, liver cirrhosis, ascites, portal vein invasion, esophageal varix, number of hyperthermia, chemotherapy, total bilirubin level, Karnofsky perfomance status. Results : The overall 1-year survival was $24.2\%$, with a mean survival of 10months. Of 33 patients, tumor regression (PR+MR) was seen in $30.4\%$, no response was seen in $52.2\%,\;17.4\%$ patient was progressed. In patients who had tumor regression, the overall 1-year survival was $42.1\%$ with a mean survival of 14 months. Factors influencing the survival were sex (p=0.05), tumor type (p=0.0248), Child's classification (p=0.0001), liver cirrhosis (p=0.0108), ascites (p=0.0009), and Karnofsky perfomance status (p=0.0028). Complications developed in 28 patients, including 18 hot pain,5 fat necrosis, 3 transient fever, 2 nausea and vomiting. Conclusion : In this study, the results suggests that combined radiotherauy and hyperthermia may improve the survival rate of hepatoma.

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Talin-1 and Non-invasive Fibrosis Models in the Assessment of Patients with Hepatocellular Carcinoma

  • Alsebaey, Ayman;Ahmedy, Iman Aly
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.4077-4082
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    • 2016
  • Background: Hepatocellular carcinoma (HCC) is a dreadful complication of end stage liver disease with high morbidity and mortality. Aim: The aim was to assess the role of serum talin-1 and non-invasive fibrosis in patients with HCC. Materials and Methods: A total of eighty seven subjects were enrolled, with 22 two healthy individuals as a control group (n=22), 22 patients in the cirrhosis group and finally 43 in the group with HCC diagnosed with positive triphasic CT abdomen criteria. Serum talin-1 and noninvasive fibrosis parameters were assessed in all subjects. Results: Compared to the cirrhosis group, patients with HCC had higher serum talin-1 ($32.9{\pm}12.6$ vs. $11.1{\pm}2.79ng/ml$), FIB4 ($9.96{\pm}15.3$ vs. $2.90{\pm}1.87$) and $fibro-{\alpha}$ ($10.9{\pm}18.1$ vs. $1.55{\pm}0.28$) but not fibrosis index scores ($4.47{\pm}0.95$ vs. $4.98{\pm}0.96$; p=0.046). Patients with large focal lesions (${\geq}5cm$) had different ALBI scores ($-1.02{\pm}0.63$ vs. $-1.72{\pm}0.59$; p=0.001) serum talin-1 ($9.72{\pm}13.81$ vs. $28.6{\pm}38.89ng/ml$; p=0.007) and fibrosis index scores ($0.85{\pm}0.99$ vs. $4.20{\pm}4.85$; p=0.026). No statistical differences were noted between patients with and without portal vein thrombosis. For detection of HCC, serum talin-1 had 97.7% sensitivity and 100% specificity with a 17.2 ng/ml cutoff. AFP at a 13.7 ng/ml cutoff had 72.1% sensitivity and 6.3.6% specificity. The cutoff for the $fibro-{\alpha}$ score was 1.61 with 81.4% sensitivity and 77.3% specificity. Serum talin-1 (odds=1.08; C.I=1.016-1.150; p=0.014), fibrosis index score (odds=2.35; C.I=1.055-5.217; p=0.037) and the ALBI score (odds=6.9; C.I=1.924-24.708; p=0.003) were predictors of large focal lesions. Conclusions: Serum talin-1, AST/ALT ratio, $fibro-{\alpha}$ score are useful for the assessment of HCC patients.

Histopathological studies on melano - macrophage centers (MMCs) in spleen and head kidney of immuno - modified tilapia, Oreochromis niloticus (틸라피아(Oreochromis niloticus)의 면역활성변화와 Melano - Macrophage Centers (MMCs)의 행동특성에 관한 병리조직학적 연구)

  • Park, Jeong-Hee;Huh, Min-Do
    • Journal of fish pathology
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    • v.7 no.2
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    • pp.127-149
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    • 1994
  • Histopathological studies on the two lymphomyeloid organs of spleen and head kidney in tilapia, Oreochromis niloticus, were carried out to clarify the significance on the morphological characteristics of melano - macrophage centers (MMCs) which are varied in different physiological and pathological conditions of teleosts. To examine the histological changes by the artificial modification of the immunological states, tilapia were treated intraperitoneally with FKC and LPS of Edwardsiella tarda, and orally with dexamethasone, and then followed by the intraperitoneal injection of colloidal carbon for chasing the macrophages. There were marked differences in phagocytic avidity of macrophages, and accumulating patterns of carbon - ladening macrophages into the MMCs among the test groups. In the non - pretreated control group, carbon - ladening macrophages were densely accumulated at 12th and 20th day within the MMCs of head kidney and spleen, respectively. And, in the groups treated with bacterial antigens (FKC & LPS), the macrophages were more rapidly and densely aggregated within MMCs. But in the group with dexamethasone, only a few carbon particles were detected in both organs. Any compactly isolated form of particles was not found in this group. From the present results, it was strongly suggested that certain changes in immunological states of tilapia influence on the morphology of MMCs including the frequency of appearance, sizes, aggregating patterns or outlines. Therefore, morphology of MMCs would be very important in the interpretation for histopathological findings seen in the teleost's lymphomyeloid organs.

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Rotavirus-associated neonatal necrotizing enterocolitis (로타바이러스 감염이 관련된 신생아 괴사성 장염)

  • Seo, Hyun Joo;Jung, Yu Jin;Park, Soo Kyung;Choi, Seo Hui;Lee, Ji Hyuk;Kim, Myo Jing;Chang, Yun Sil;Park, Won Soon
    • Clinical and Experimental Pediatrics
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    • v.52 no.1
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    • pp.56-60
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    • 2009
  • Purpose : This study aimed to test whether rotavirus-associated necrotizing enterocolitis (RV+NEC) produced different clinical findings or outcomes from those of non-rotavirus necrotizing enterocolitis (RV-NEC). Methods : Eight patients from the RV+NEC group and 22 patients from the RV-NEC group diagnosed with modified Bell stage II or higher NEC were selected for this study. Fecal specimens from all infants were tested for rotavirus infection using a monoclonal antibody-based enzyme immunoassay (EIA). Clinical, radiographic, and clinical outcome data were analyzed retrospectively. Results : RV+NEC infants had a significantly higher birth weight and were born at a significantly higher gestational age ($33.5{\pm}3.3$ weeks vs. $29.3{\pm}4.4$ weeks; P=0.01). There were no differences in the occurrence of thrombocytopenia, mural gas, and pneumoperitoneum between the 2 groups. However, portal vein gas was more common in the RV+NEC group (88% vs. 9%; P<0.01). Neither the incidence of Bell stage III (or higher) NEC nor surgical intervention differed between the two groups. The number of complications and mortality rates were also similar. Conclusion : Rotavirus-associated NEC occurs in infants with a higher birth weight and those born at a greater gestational age. However, the severity of the condition and the resulting outcomes did not differ from those for infants affected by non-rotavirus NEC.

Pharmacokinetic Preformulation Study of rH IL-2 (인터루킨-2의 제제설계를 위한 체내 동태학적 연구)

  • Seo, Min-Seok;Shim, Chang-Koo;Kwon, Jong-Bum;Na, Do-Sun;Lee, Sun-Bok;Hahm, Kyung-Soo;Han, Moon-Hi
    • YAKHAK HOEJI
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    • v.34 no.4
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    • pp.238-243
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    • 1990
  • Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

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Effect of Formaldehyde Treated Rape Seed Oil Cake Based Diet Supplemented with Molasses on Growth Rate and Histopathological Changes in Goats

  • Sahoo, B.;Walli, T.K.;Sharma, A.K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.7
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    • pp.997-1003
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    • 2006
  • An experiment with twenty crossbred goat kids (male) of 2-3 months old, weighing about 12 kg was conducted to study the effect of feeding formaldehyde treated rape seed oil cake based diet supplemented with molasses on growth rate and histopathological changes of different organs. Goats were randomly divided into four groups of 5 animals each and were individually fed for a period of 120 days. The animals in group I (URC) and II (URCM) were fed concentrate mixture (CM-I) containing untreated rape seed oil cake (30%) while, the animals in group III (TRC) and IV (TRCM) were offered concentrate mixture (CM-II) containing formaldehyde treated rape seed oil cake. Further, molasses as energy source was additionally supplemented with the concentrate mixture at the rate of 8% of concentrate mixture on dry matter basis to animals in group II and IV. All the animals were maintained on roughage (Berseem hay:wheat straw = 2:1) and concentrate in 50:50 ratio. Average daily gain (g/d) of animals in group IV was significantly (p<0.05) higher than that in group I., but at par with group II and III. Feed conversion efficiency was also significantly (p<0.05) higher in group IV (10.14) than group I and II but at par with group III. The growth rate however increased by 50.2% in group IV showing more consistency in maintaining highest growth rate due to better balance of nutrients. At the end of four months of feeding trial, two animals from each group were sacrificed for histopathological study of different organs. Significant histopathological changes in liver, heart, lungs tissue of animals fed untreated rape seed oil cake diet were recorded which were totally absent in the organ of animals fed formaldehyde treated cake. The liver tissue of goats receiving control diet (containing untreated rape seed oil cake) were found to be associated with engorged central vein and blood vessels. Hepatocytes were swollen, pale and degenerated with cellular infiltration and fibrosis of portal areas. The muscles of heart were found to have intermyofibral edema. Emphysema accompanied by dilated and ruptured alveoli was also recorded in lung tissue. However, histopathological examination of various tissues of goats fed formaldehyde treated cake diet did not exhibit any degenerative changes. Additional supplementation of molasses with or without treated cake diet, apparently did not have any significant effect on ameliorating the above degenerative changes.

Serum Peroxiredoxin3 is a Useful Biomarker for Early Diagnosis and Assessemnt of Prognosis of Hepatocellular Carcinoma in Chinese Patients

  • Shi, Liang;Wu, Li-Li;Yang, Jian-Rong;Chen, Xiao-Fei;Zhang, Yi;Chen, Zeng-Qiang;Liu, Cun-Li;Chi, Sheng-Ying;Zheng, Jia-Ying;Huang, Hai-Xia;Yu, Fu-Jun;Lin, Xiang-Yang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.2979-2986
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    • 2014
  • Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

The Analysis of Study Trends of Wild ginseng, Bovis Calculus, Ursi Fel, Moschus and The Study on Applied Possibility as Obesity medications (산삼, 우황, 웅담, 사향의 연구 동향 분석 및 비만 치료제로써의 응용 가능성 탐색 연구)

  • Kim, Min-Woo;Song, Yun-Kyung;Lim, Hyung-Ho
    • Journal of Korean Medicine for Obesity Research
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    • v.11 no.2
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    • pp.41-68
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    • 2011
  • Objectives: After organizing segmentations related to obesity from classics and each studies, we would like to examine the value of wild ginseng, bovis calculus, ursi fel and moschus as a obesity medicine. Methods: We found out 4 drugs which are wild ginseng, bovis calculus, ursi fel and moschus from the classics, such as "Shin-Nong-Bon-Cho-Kyung", "Myoung-Eui-Byul-Lok", "Bon-Cho-Gang-Mok", "Bon-Cho-Jong-Shin", "Bon-Cho-Bi-Yo", "Bon-Cho-Gu-Jin" and "Deuk-Bae-Bon-Cho", we searched websites such as RISS, Korean traditional knowledge portal, the society of Korean medicine for obesity research, Korean pharmacopuncture institute, the Korean academy of oriental rehabilitation medicine and Korean acupuncture & moxibustion society as well. Results: 1. We couldn't find the contents related to the efficacy of improving obesity through wild ginseng, bovis calculus, ursi fel and moschus from the classics. 2. Wild ginseng had a study dealing with the efficacy of anticancer, obesity, toxicity, immunity, sulfation, diabetes, plasma proteins, depression, hypertension, endometriosis and hair loss. Especially among 6 studies related to obesity, apart from the study that treated extract of wild ginseng directly to the cell or oral administration to the animals, also have studies that had an efficacy of improving obesity through injecting pharmacopuncture to acupuncture point and vein, etc. 3. Bovis calculus had a study about efficacy related to arthritis, liver, inflammation of cornea, obesity, anticancer, immunity, antacid, heart, lumbar pain, hypertension, toxicity, a digestive organ and sasang constitution, especially in case of obesity, had each studies about oral administration of complex prescription and about cell unit experiment of pharmacopuncture. 4. Ursi fel had a study about efficacy related to liver, arthritis, inflammation of cornea, immunity, obesity, anticancer, antacid, lumbar pain, digestive organ, toxicity, cell protection, skin ailment, etc. Especially in case of obesity, had each studies about oral administration of animal experiment and about cell unit experiment of pharmacopuncture. 5. Moschus had a study about efficacy related to liver, the central nervous system, arthritis, inflammation of cornea, immunity, obesity, anticancer, hypertension, heart, lumbar pain, etc. Especially in case of obesity, had one study about oral administration of complex prescription. Conclusion: Through the result of probability as a obesity medicine of wild ginseng, bovis calculus, ursi fel and moschus, we could identify the possibility of each drug as a obesity medicine. Also in the future, it is considered that studies about one or complex prescription and pharmacopuncture as a obesity medicine will be needed.

Changes in the Concentration and Localization of Accumulated Mercury in Kidney, Liver, and Spleen of Mice over Time (생쥐 신장, 간, 비장 내 시간에 따른 수은 농도 변화와 수은 화합물의 위치)

  • Kim, Yu Seon;Kim, Young Eun;Cho, Hyun Wook
    • Journal of Life Science
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    • v.29 no.8
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    • pp.879-887
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    • 2019
  • This study investigated the localization and changes in the concentration of injected mercury in the kidney, liver, and spleen of mice. To evaluate changes in the concentration of mercury over time, the mice were euthanized 10, 150, and 300 days post-treatment. Localization of accumulated mercury was identified by the autometallography method. Mercury was densely located in the supranuclear cytoplasm of epithelial cells of proximal tubules of the kidney but was not detected in the glomerulus 10 days post-treatment. In the liver, mercury was mainly found in hepatocytes around the portal vein and in sinusoidal Kupffer cells 10 days post-treatment. Mercury was scattered throughout both white and red pulp of the spleen 10 days post-treatment. In terms of changes in the concentration of mercury, the levels were lower in the renal cortex and medulla 150 and 300 days post-treatment as compared with those 10 days post-treatment. Mercury was found at low concentrations in liver hepatocytes 150 and 300 days post-treatment. The mercury concentration was also low in both the white and red pulp of the spleen 150 and 300 days post-treatment. Therefore, the concentrations of accumulated mercury in the kidney, liver, and spleen 150 and 300 days post-treatment were lower than those 10 days post-treatment. We identified the localization of mercury in cells and tissues of several organs and observed that accumulated mercury in organs decreased naturally over time.