• Applied Microscopy
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• v.40 no.2
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• pp.73-80
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• 2010

Liver regeneration is a result of highly coordinated proliferation of hepatocytes and nonparenchymal liver cells. Partial hepatectomy (PH) is the most often used stimulus to study liver regeneration because, compared with other methods that use hepatic toxins, it is not associated with the tissue injury and inflammation, and the initiation of the regenerative stimulus is precisely defined. Granulocyte macrophage-colony stimulating factor (GM-CSF), which is a cytokine able to regulate the proliferation and differentiation of epithelial cells, was first identified as the most potent mitogen for bone marrow. Particularly, rrhGM-CSF, which is highly glycosylated and sustained longer than any other types of GM-CSF in the blood circulation, was specifically produced from rice cell culture. In this experiment, effects of rrhGM-CSF administration were evaluated in the regenerating liver after 78% PH of rats. Morphological changes induced by PH were characterized by destroyed hepatocyte plate around the central vein and enlarged nuclear cytoplasmic ratio and increased hepatocytes with two nuclei. And then, proliferation of liver cells (parenchymal and nonparenchymal) and rearrangement of plates and lobules seemed to be carried out during liver regeneration. These alterations in the experimental group preceded those of the control. Since proliferating cell nuclear antigen (PCNA) is known to be a nuclear protein maximally elevated in the S phase of proliferating cells, the protein was used as a marker of liver regeneration after PH in rats. PCNA levels by western blot analysis and immunohistology were compared between the two groups. PCNA protein expression of two groups at 12 hr and 24 hr after injury showed similar pattern. The protein expression showed the peak at 3 days in both groups, however, the protein level of the experimental group was higher than that of the control. On immunohistochemical observations, the reaction product of PCNA was localized at the nuclei of proliferating cells and the positive reaction in experimental group at 3 days was clearly stronger than that in control group. The results by Western blotting and immunohistology for PCNA showed similar pattern in terms of the protein levels. In conclusion, rrhGM-CSF administration during liver regeneration after 78% PH accelerated breakdown and restoration of the hepatic plate and expression of PCNA. These results suggest that rrhGM-CSF might play an important role during liver regeneration in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.238-242
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• 2014

Here we described 2 cancer patients treated by acupuncture for abdominal pain as a complication of bowel obstruction. The patient 1, 43-year-old man was treated with surgery, radiotherapy and chemotherapy for rectal cancer. Two years after surgery, he complained of acute abdominal pain due to small bowel adhesion band. Bowel obstruction and symptoms were not improved by conservative therapy like as fasting, keeping Levin tube, and fluid therapy. 4 months later, he could eat a little rice water, but ileus and abdominal pain persisted despite of applying opiod drug and patch. Got started on acupuncture, electroacupuncture(ST-36) and moxa treatment, pain was relived gradually. He could stop opioids 1 month later and ileus was improved after acupuncture therapy for 2 months. The patient 2, 65-year-old woman got hepatectomy, cholecystectomy, and chemotherapy with cholangiocarcinoma. 6 months after surgery, she got laparotomy again for biopsy of new mass around ascending colon. She started eating after gas passing, but felt abdominal distension. Diffuse paralytic ileus was diagnosed by abdominal X-ray, and she got started conservative therapy. During ST-36 electroacupuncture therapy, symptoms like abdominal pain and distension were improved and could stop opiod patch. But eating aggravated ileus again and clinical finding of mechanical bowel obstruction was appeared. Based on these cases, acupuncture and moxa therapy could be helpful for improving abdominal pain and ileus, but possibility of malignant bowel obstruction should be considered especially in cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5195-5200
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• 2014

Background: The purpose of this study was to analyze our series of liver resections for metastatic colorectal carcinoma (mCRC) to determine prognostic factors affecting survival and to evaluate the potential roles of neoadjuvant or adjuvant chemotherapy. Materials and Methods: Ninety-nine patients who underwent metastasectomy for liver metastases due to colorectal cancer at the Department of Medical Oncology, 9 Eylul University Hospital between 1996 and 2010 were evaluated in this study. The patients were followed through July 2013. Demographic, perioperative, laboratory, radiological and chemotherapy as well as survival data were obtained by retrospective chart review. Results: In 47 (47.5%) patients, liver metastases were unresectable at initial evaluation; the remaining 52 (52.5%) patients exhibited resectable liver metastases. Simultaneous hepatic resection was applied to 52 (35.4%) patients with synchronous metastasis, whereas 5 (64.5%) patients underwent hepatic resection after neoadjuvant chemotherapy. Forty-two patients with metachronous metastasis underwent hepatic resection following neoadjuvant chemotherapy. R0 resection was obtained in 79 (79.8%) patients. A second hepatectomy was performed in 22 (23.2%) patients. Adjuvant chemotherapy was given to 85 (85.9%) patients after metastasectomy. The median disease-free and overall survivals after initial metastasectomy were 12 and 37 months, respectively, the 1-year, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates being 46.5%, 24.3% and 17.9%and 92.3%, 59.0% and 39.0%, respectively. On multivariate analysis, the primary tumor site, tumor differentiation, resection margin and DFS were independent factors predicting better overall survival. Conclusions: In selected cases, hepatic metastasectomy for mCRC to the liver can result in long-term survival. Neoadjuvant chemotherapy did not exert a positive effect on DFS or OS. Adjuvant chemotherapy also did not appear to impact DFS and OS.

• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.117-129
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• 2000

This study was carried out to examine proliferative activity and expression of c-myc oncoprotein and p2lras in normal and preneoplastic rat livers induced by an in vivo mid-term chemical carcinogenesis assay. Sixty, six-week-old male specific pathogen free Sprague-Dawley male rats were randomly divided into five groups. Group I was received a single intraperitoneal(IP) dose(200mg/kg) of diethylnitrosamine(DEN). Group 2(10 rats) was operated partial hepatectomy(PH) and Group 3 was received IP(200mg/kg) DEN, fed two weeks later with 500ppm of phenobarbital(PB). Group 4 was received IP(200mg/kg) DEN, fed two weeks later 500ppm(PB) and PH at week 3 after the onset of experiment. While group 5(20 rats) was not treated and used as a control group. All the rats were sacrificed at age 14 weeks except 10 rats from group 5 were sacrificed at the onset of experiment. Livers of all rats were examined for 5-bromo-2'-deoxyuridine(BrdU) incoporation, proliferating cell nuclear antigen(PCNA), silver-binding nucleolar organizer regions(AgNORs) counts per nucleus and expression of c-myc oncoprotein and p21ras. Both the number and area of the preneoplastic lesions were significantly(p<0.01) compared to other groups. A significant(p<0.01) increase in immunoreactive cells were detected in preneoplastic hepatocytes in Groups 3 and 4 by PCNA and BrdU immunohistochemical stain. The number of the positive cells were significantly(p<0.05) lower in normal 14-week-old rats than those of 6-week-old rats. The results showed that proliferative activity of the hepatocytes was increased by treatment with DEN, PH and PB. Meanwhile, AgNORs counts per nucleus were significantly(p<0.05) increased in the preneoplastic hepatocytes of rats in both groups 3 and 4. The expression of c-myc oncoprotein and p21ras were more readily localized within the hepatic preneoplastic lesions such as hyperplastic nodules. Especially, group 4 showed significantly (p<0.05) overexpressed levels compared to groups 1 and 3. These findings suggest that PCNA, BrdU and AgNORs are significantly increased and c-myc oncoprotein and p21ras are significantly overexpressed in hepatic preneoplastic lesions induced by mid-term carcinogenesis. So these parameters can be an effective markers for hepatic prencoplastic lesions.

• Korean Journal of Radiology
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• v.23 no.2
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• pp.180-188
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• 2022

Objective: To validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens as the reference standard. Materials and Methods: This retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0-F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal-Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis. Results: Inter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97-0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0-F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97-0.98 (sensitivity 91.2%-95.9%, specificity 90.7%-99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0-F3 stages. Conclusion: The 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.3
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• pp.258-263
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• 2023

Backgrounds/Aims: Hemangiomas are the most common benign liver lesions; however, they are usually asymptomatic and seldom require surgery. Enucleation and resection are the most commonly performed surgical procedures for symptomatic lesions. This study aims to compare the outcomes of these two surgical techniques. Methods: A retrospective analysis of symptomatic hepatic hemangiomas (HH) operated upon between 2000 and 2021. Patients were categorized into the enucleation and resection groups. Demographic profile, intraoperative bleeding, and morbidity (Clavien-Dindo Grade) were compared. Independent t-test and chi-square tests were used for continuous and categorical variables respectively. p-value of < 0.05 was considered significant. Results: Sixteen symptomatic HH patients aged 30 to 66 years underwent surgery (enucleation = 8, resection = 8) and majority were females (n = 10 [62.5%]). Fifteen patients presented with abdominal pain, and one patient had an interval increase in the size of the lesion from 9 to 12 cm. The size of hemangiomas varied from 6 to 23 cm. The median blood loss (enucleation: 350 vs. resection: 600 mL), operative time (enucleation: 5.8 vs. resection: 7.5 hours), and postoperative hospital stay (enucleation: 6.5 vs. resection: 11 days) were greater in the resection group (statistically insignificant). In the resection group, morbidity was significantly higher (62.6% vs. 12.5%, p = 0.05), including one mortality. All patients remained asymptomatic during the follow-up. Conclusions: Enucleation was simpler with less morbidity as compared to resection in our series. However, considering the small number of patients, further studies are needed with comparable groups to confirm the superiority of enucleation over resection.

• Korean Journal of Radiology
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• v.21 no.8
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• pp.987-997
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• 2020

Objective: Measurement of the liver and spleen volumes has clinical implications. Although computed tomography (CT) volumetry is considered to be the most reliable noninvasive method for liver and spleen volume measurement, it has limited application in clinical practice due to its time-consuming segmentation process. We aimed to develop and validate a deep learning algorithm (DLA) for fully automated liver and spleen segmentation using portal venous phase CT images in various liver conditions. Materials and Methods: A DLA for liver and spleen segmentation was trained using a development dataset of portal venous CT images from 813 patients. Performance of the DLA was evaluated in two separate test datasets: dataset-1 which included 150 CT examinations in patients with various liver conditions (i.e., healthy liver, fatty liver, chronic liver disease, cirrhosis, and post-hepatectomy) and dataset-2 which included 50 pairs of CT examinations performed at ours and other institutions. The performance of the DLA was evaluated using the dice similarity score (DSS) for segmentation and Bland-Altman 95% limits of agreement (LOA) for measurement of the volumetric indices, which was compared with that of ground truth manual segmentation. Results: In test dataset-1, the DLA achieved a mean DSS of 0.973 and 0.974 for liver and spleen segmentation, respectively, with no significant difference in DSS across different liver conditions (p = 0.60 and 0.26 for the liver and spleen, respectively). For the measurement of volumetric indices, the Bland-Altman 95% LOA was -0.17 ± 3.07% for liver volume and -0.56 ± 3.78% for spleen volume. In test dataset-2, DLA performance using CT images obtained at outside institutions and our institution was comparable for liver (DSS, 0.982 vs. 0.983; p = 0.28) and spleen (DSS, 0.969 vs. 0.968; p = 0.41) segmentation. Conclusion: The DLA enabled highly accurate segmentation and volume measurement of the liver and spleen using portal venous phase CT images of patients with various liver conditions.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.2
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• pp.134-143
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• 2024

Backgrounds/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. Methods: We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. Results: The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). Conclusions: HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.650-659
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• 1999

Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

• Journal of Food Hygiene and Safety
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• v.6 no.1
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• pp.1-12
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• 1991

Fischer 344 rats aged six weeks were diYided into four groups and group 1, 2, and 3 of rats were given an intraperitoneal injection of diethylnitrosamine at 200 mg/kg body weight and group 4 was given saline alone. Two weeks after beginning of the experiment, group 1 and 2 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for four weeks. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. During the last two weeks, group 1 and 3 of rats were received subcutaneously 3 consecutive weekly doses of iron dextran at 0.125 ml/100 g body weight. Subcutaneous injection of iron dextran resulted in hepatic siderosis in group 1 and 3 of rats. Pre neoplastic nodules were identified histopathologically by two markers, resistance to exogenous iron accumulation and glutathione S-transeferase placental form (GST-P) activity, while early carcinogen induced foci were hardly resistant to iron accumulation and though a few lesions were identified, it could hardly be distincted from normal hepatocytes of surroundings. However, GST-P positive nodules as well as foci were clearly distincted from normal hepatic cells of surroundings. In the quantitative analysis of carcinogen-induced nodules and foci, more lesions were detected by immunohistochemical method for GST-P than by prussian blue staining for resistant to iron accumulation. It is concluded that immunohistochemical marker for GST-P is more sensitive and reliable than iron-resistance marker, and that iron-resistance is not useful marker for early detection of carcinogen-induced hepatic lesions.