• Journal of Veterinary Clinics
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• v.38 no.4
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• pp.179-183
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• 2021

A 12-year-old male American Cocker Spaniel was diagnosed with a type of chronic hepatits (CH) called cholangioheaptits. Routine supportive medication was administered to the patient, and ex vivo boosted immune cell (EBI-C) therapy was used for the treatment. A histopathologic examination of the liver 19 months later revealed that the cholangiohepatitis had progressed to cholangiocarcinoma. The medication and immune cell therapy was maintained. Two months after the new diagnosis, the patient's state worsened, and the dog died 635 days after the first visit. EBI-C therapy is a type of immunotherapy, where immune cells are isolated from the patient's peripheral blood mononuclear cells, expanded ex vivo, and then infused into the patient intravenously every two weeks. EBI-Cs (mean: 2.78 × 10⁸ cells) were obtained 38 times and infused every two weeks. Most EBI-C were T-lymphocytes (99.24% of total EBI cells). T-lymphocytes produce large interferon (IFN)-γ, and IFN-γ inhibits liver fibrosis in dogs with CH. Moreover, in bile duct cancer, an increase in T-lymphocytes correlates with decreasing tumor invasion and metastasis. Thus, we propose that EBI-C therapy is applicable as a new supportive therapy for canine liver disease if other treatments like drug medication, surgery, or radiation are unavailable.

• Journal of Hospice and Palliative Care
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• v.19 no.4
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• pp.331-334
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• 2016

Purpose: Advanced cancer may accompany cold sweat as paraneoplastic symptom. Few studies have been performed on the efficacy of non-steroid anti-inflammatory drug (NSAID) in advanced cancer patients who sweated without fever. Methods: To select study participants, medical records were retrospectively reviewed for patients who satisfied the following criteria: 1) incurable, advanced solid cancer; 2) Cold sweating of 4 or higher on the numeric rating scale (NRS) 4; 3) No evidence of infection or hypoglycemia; 4) No newly started opioid or anti-hormonal agents within one month; 5) NSAID prescription for the management of cold sweating and 6) Documented NRS information before and after NSAID administration. Results: A total of 13 patients were selected after excluding four patients due to lack of NRS information or fever. The mean age was 59 years old (range: 50~71), and nine patients (69%) were male. Bile duct cancer was the most common primary tumor followed by pancreatic cancer, gastric cancer and prostate cancer. The mean NRS of cold sweating dropped from baseline 6.5 (min-max: 4~10) to 1.9 at the follow-up assessment (min-max: 0~5). The mean follow-up period was 9.1 days (range: 2~30 days) from NSAID treatment to assessment. Conclusion: NSAID was effective medication for management of sweating without fever in patients with advanced cancer.

• Parasites, Hosts and Diseases
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• v.58 no.6
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• pp.647-652
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• 2020

Clonorchis sinensis is the most common fish-borne intestinal parasite in Korea. The aim of the present investigation was to survey the status of C. sinensis infection and analyze associated risk factors in residents of Haman-gun, Gyeongsangnam-do. A total of 5,114 residents from 10 administrative towns/villages voluntarily agreed to participate in the study, which comprised fecal examination, a questionnaire survey for risk factors, ultrasonography, and enzyme-linked immunosorbent assay for cancer biomarker detection in the blood. We detected C. sinensis eggs in 5.3% of the subjects. By region, Gunbuk-myeon had the highest number of residents with C. sinensis eggs. The infection rate and intensity were higher in male than in female residents. Based on the risk factor questionnaire, infection was highly associated with drinking, a history of C. sinensis infection, and the practice of eating of raw freshwater fish. Extension of the bile duct, infection intensity, and cancer biomarker detection significantly correlated with the presence of eggs in the study population. In conclusion, the development of feasible, long-term control policies and strategies for the elimination of C. sinensis in Korea is still required.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1041-1048
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• 2009

The development of skin metastasis is usually a morbid prognostic feature although they occur infrequently. Adenocarcinomas account for up to about 70% of all metastatic skin cancer. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site because they don't have distinctive histological features. For this reason, immunohistochemistry have been used to help identify the origin of metastatic adenocarcinomas. This study performed immunohistochemical staining with metastatic adenocarcinomas of the skin using a variety of antisera to find out characteristic immunohistochemical findings of them. This study was made upon the 29 cases of metastatic adenocarcinomas of the skin, which had been confirmed histopathologically in Chonbuk National University Hospital from January, 1986 to April, 2006, Paraffin blocks were colledted and homemade tissue arrays were made. We performed immunohistochemical staning using 12 antibodies (MUC1, 2, 5AC, 6, cytokeratin (CK) 7, 20, thyroid transcription factor-1 (TTF-1), estrogen receptor (ER), progesterone receptor (PR), beta-catenin, cox-2, claudin-1). The mean age at the time of diagnosis was 60.7 years and the male to female ratio was 1.2:1.0. The most common primary site was lung, followed by stomach and colorectum. MUC1 was expressed by most colorectal, breast and lung adenocarcinoma. MUC2 was expressed infrequently. MUCSAC was expressed by most gastric and colorectal cancer MUC6 was not specific of any primary site in this series. CK7+/CK20+immunophenotype was observed in gastric, lung, colorectal adenocarcinoma. CK7+/CK20- immunophenotype was observed in breast, lung, endometrial, uterine cervical, bile duct adenocarcinoma, while CK7-/CK20+ immunophenotype was observed only in colorectal adenocarcinoma. This results show the utility of TTF-1 to confirm the pulmonary origin. On the other hand ER and PR were not useful markers to assess the origin of primary tumor in this series.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6257-6260
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• 2013

Gallstone disease is a major surgical problem in many populations; it is probably related to diet, especially excessive consumption of meat. The objective of this study was to determine the chemical composition of gallstones and their association with neoplastic changes including cholangiocarcinomas in cholecystectomised patients. The chemical composition of gallstones from 40 patients (8 males and 32 females) was analyzed. This is a prospective study performed in Baquba teaching hospital in the period from 1/10/2012 to 1/1/2013 in which we collected the gallstones for the patients who underwent cholecystectomy, whether open or laparoscopic. The stones were classified according to their chemical composition as a mixed stones (MS), and examined using a stone analysis set (chemical qualitative method) for calcium, magnesium, phosphate, uric acid and oxalate which was used reagent for qualitative determination of main individual components of stones. The results of this study showed the highest incidence of gallstones in the age group 40-49 was 13 cases followed by 11, 8 and 4 cases for age groups 30-39, 50-59, 20-29 and 60 and above, respectively. The chemical analysis showed the majority of gallstones were mixed, 38 containing calcium followed by 37 cases with uric acid, 28 with magnesium, and 25 and 22 stones with oxalate and phosphate, respectively. Microscopically, we confirmed neoplastic changes (17.5%) as cholangiocarcinomas (CCCs) (7.55%) and dysplastic cells of carcinoma in situ in 4 (10%), 31 (77.5%) cases were chronic cholecystitis and 2 (5%) cases were acute cholecystitis with empyema out of bile duct disorders patients. In conclusion, majority of cases had mixed gallstones that involved five and four of inorganic chemicals of calcium, magnesium and phosphate, the highest incidence of gallstones in age group 40-49 years old was 13 cases, and neoplastic changes were confirmed (17.5%) including CCCs, (7.5%) and dysplastic cells of carcinoma in situ (10%), while 31 (77.5%) cases were chronic cholecystitis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.37-44
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• 2016

Several infectious agents are considered to be causes of cancer in human, mainly hepatitis B and C viruses, high-risk human pailloma viruses, Helicobacter pylori, Clonorchis sinensis, and Opisthorchis viverrini. Here we described the evident research and the association between Helicobacter spp. and biliary tract cancer particularly cholangiocarcinoma (CCA). Global epidemiological studies have suggested that Helicobacter spp. are possible risk factors for biliary tract diseases. Molecular studies support a linkage of Helicobacter spp. with CCA development. H. pylori, H. bilis, and H. hepaticus, are found in CCA, but the most common species are H. pylori and H. bilis. The type of CCA are associated with Helicobacter spp. include extrahepatic CCA, and common bile duct cancer. Up to the present, however, the results from different regions, materials and methods, sub-sites of cancer, and controls have not been consistent, thus introducing heterogeneity. Therefore, a comparison between co-Helicobacter spp.-CCA in the countries with low and high incident of CCA is required to settle the question. Furthermore, clarifying variation in the role of Helicobacter species in this CCA, including pathogenesis of CCA through enhanced biliary cell inflammation and proliferation, is necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9511-9515
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• 2014

Cholangiocarcinoma (CCA) is a cancer of the bile duct epithelial cells. The highest incidence rate of CCA with a poor prognosis and poor response to chemotherapy is found in Southeast Asian countries, especially in northeastern Thailand and Lao PDR. Cathepsin B is a lysosomal cysteine protease which is regulated by cysteine proteinase inhibitors such as cystatin C. Elevation of cathepsin B levels in biological fluid has been observed in patients with inflammatory diseases and many cancers. We aimed to investigate the serum cathepsin B and cystatin C levels of CCA patients to evaluate the feasibility of using cathepsin B and cystatin C as markers for the diagnosis of CCA. Fifty-six sera from CCA patients, 17 with benign biliary diseases (BBD) and 13 from controls were collected and the cathepsin B and cystatin C levels were determined. In addition, cathepsin B expression was investigated immunohistochemically for 9 matched-pairs of cancerous and adjacent tissues of CCA patients. Serum cathepsin B, but not cystatin C, was significantly higher in CCA and BBD patient groups compared to that in the control group. Consistently, all cancerous tissues strongly expressed cathepsin B while adjacent tissues were negative in 7 out of 9 cases. In contrast, serum cystatin C levels were comparable between CCA and control groups, although serum cystatin C levels in the BBD group was higher than that in the control or CCA groups. When the serum cathepsin B to cystatin C ratio was calculated, that of the CCA group was significantly higher than that of the control group, and, although statistically not significant, the ratio of CCA group showed a trend to be higher than that of the BBD group. Thus, the cathepsin B to cystatin C ratio might be used as an alternative marker for aiding diagnosis of CCA.

• Parasites, Hosts and Diseases
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• v.51 no.6
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• pp.711-717
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• 2013

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.

• Radiation Oncology Journal
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• v.14 no.2
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• pp.129-136
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• 1996

Purpose : To evaluate the effectiveness and tolerance of patients of external beam radiotherapy for carcinoma of the extrahepatic biliary system (EHBS) including gall bladder (GB) and extrahepatic bile ducts (EHBD) and to define the role of radiotherapy for these tumors. Methods and Materials : We retrospectively analyzed the records of 43 patients with carcinoma of the EHBS treated with external beam radiotherapy at our institution between April, 1986 and Julr, 1994. Twenty three patients had GB cancers and remaining 20 patients did EHBD cancers. Of those 23 GB cancers, 2 had Stage II, 12 did Stage III and 9 did Stage IV disease, respectively. Male to female ratio was 11 to 12. Fifteen patients underwent radical surgery with curative intent and 8 patients did biopsy and bypass surgery alone All of the patients except for 3 patients were treated with 4500 cGy or higher doses postoperatively Follow up periods ranged from 11 to 82 months. Of those 20 EHBD cancers, one had Stage I, 2 did Stage II, 10 did Stage III and 7 did Stage IV disease, respectively. Male to female ratio was 16 to 4 Sixteen patients underwent Whipple's procedure or resection and drainage with curative aim and remaining 4 patients did bypass surgery alone Postoperatively 16 patients were irradiated with 4500 cGy or higher doses and 4 patients with 3180 to 4140 cGy Follow up periods ranged from 8 to 34 months. Results : Overall median survival time of patients with GB cancer was 11 months. Median survival time for Patients with Stage III and IV disease were 14 months and 5 months, respectively. Corresponding two rear survival rates were $36\%$(4/11) and $13\%$(1/8), respectively Those who underwent surgery with curative intent showed significantly better survival at 12 months than those who underwent bypass surgery alone($67\%$ vs $13\%$). None of the patients died of treatment related complications Median survival time for entire group of 20 EHBD patients was 10 months Median survivals of 10 Stage III and 7 Stage IV disease were 10 and 8 months, respectively. Two patients who underwent Whipple's procedure had 11 and 14 month survival and those treated with resection and drainage showed median survival of 10 month. Conclusion : Postoperative external beam radiotherapy for carcinoma of the extrahepatic biliary system is well tolerated and might improve survival of patients, especially those with resectable lesions with microscopic or gross residual disease after surgery.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.277-282
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• 2000

Purpose : Though It has been known that the to tolerance of the liver to external beam irradiation depends on the irradiated volume and dose, few data exist which Quantify this dependence. However, recently, with the development of three dimensional (3-D) treatment planning, have the tools to Quantify the relationships between dose, volume, and normal tissue complications become available. The objective of this study is to investigate the relationships between normal tissue complication probabili쇼 (WCP) and the risk of radiation hepatitis for patients who received variant dose partial liver irradiation. Materials and Methods : From March 1992 to December 1994, 10 patients with hepatoma and 10 patients with bile duct cancer were included in this study. Eighteen patients had normal hepatic function, but 2 patients (prothrombin time 73$\%$, 68$\%$) had mild liver cirrhosis before irradiation. Radiation therapy was delivered with 10MV linear accelerator, 180$\~$200 cGy fraction per day. The total dose ranged from 3,960 cGy to 6,000 cGy (median dose 5,040 cGy). The normal tissue complication probability was calculated by using Lyman's model. Radiation hepatitis was defined as the development of anicteric elevation of alkaline phosphatase of at least two fold and non-malignant ascites in the absence of documented progressive. Results: The calculated NTCP ranged from 0.001 to 0.840 (median 0.05). Three of the 20 patients developed radiation hepatitis. The NTCP of the patients with radiation hepatitis were 0.390, 0.528, 0.844(median : 0.58$\pm$0.23), but that of the patients without radiation hepatitis ranged fro 0.001 to 0.308 (median .0.09$\pm$0.09). When the NTCP was calculated by using the volume factor of 0.32, a radiation hepatitis was observed only in patients with the NTCP value more than 0.39. By contrast, clinical results of evolving radiation hepatitis were not well correlated with NTCP value calculated when the volume factor of 0.69 was applied. On the basis of these observations, the volume factor of 0.32 was more correlated to predict a radiation hepatitis. Conclusion : The risk of radiation hepatitis was increased above the cut-off value. Therefore the NTCP seems to be used for predicting the radiation hepatitis.