Machine learning-based survival rate prediction of Korean hepatocellular carcinoma patients using multi-center data.

AIM: To predict survival time of Korean hepatocellular carcinoma (HCC) patients using multi-center data as a foundation for the development of a predictive artificial intelligence model according to treatment methods based on machine learning. METHODS: Data of patients who underwent treatment for HCC from 2008 to 2015 was provided by Korean Liver Cancer Study Group and Korea Central Cancer Registry. A total of 10,742 patients with HCC were divided into two groups, with Group I (2920 patients) confirmed on biopsy and Group II (5562 patients) diagnosed as HCC according to HCC diagnostic criteria as outlined in Korean Liver Cancer Association guidelines. The data were modeled according to features of patient clinical characteristics. Features effective in predicting survival rate were analyzed retrospectively. Various machine learning methods were used. RESULTS: Target was overall survival time, which divided into approximately 60 months (= /< 60 m, > 60 m). Target distribution in Group I (total 514 samples) was 28.8%: (148 samples) less than 60 months, 71.2% (366 samples) greater than 60 months, and in Group II (total 757 samples) was 66.6% (504 samples) less than 60 months, 33.4% (253 samples) greater than 60 months. Using NG Boost method, its accuracy was 83%, precision 84%, sensitivity 95%, and F1 score 89% for more than 60 months survival time in Group I with surgical resection. Moreover, its accuracy was 79%, precision 82%, sensitivity 87%, and F1 score 84% for less than 60 months survival time in Group II with TACE. The feature importance with gain criterion indicated that pathology, portal vein invasion, surgery, metastasis, and needle biopsy features could be explained as important factors for prediction in case of biopsy (Group I). CONCLUSION: By developing a predictive model using machine learning algorithms to predict prognosis of HCC patients, it is possible to project optimized treatment by case according to liver function and tumor status.

Absent or impaired rectoanal inhibitory reflex as a diagnostic factor for high-grade (grade III-V) rectal prolapse: a retrospective study.

BACKGROUND: Clinically diagnosing high-grade (III-V) rectal prolapse might be difficult, and the prolapse can often be overlooked. Even though defecography is the significant diagnostic tool for rectal prolapse, it is noticed that rectoanal inhibitory reflex (RAIR) can be associated with rectal prolapse. This study investigated whether RAIR can be used as a diagnostic factor for rectal prolapse. METHODS: In this retrospective study, we evaluated 107 patients who underwent both anorectal manometry and defecography between July 2012 and December 2019. Rectal prolapse was classified in accordance with the Oxford Rectal Prolapse Grading System. Patients in the high-grade (III-V) rectal prolapse (high-grade group, n = 30), and patients with no rectal prolapse or low-grade (I, II) rectal prolapse (low-grade group, n = 77) were analyzed. Clinical variables, including symptoms such as fecal incontinence, feeling of prolapse, and history were collected. Symptoms were assessed using yes/no surveys answered by the patients. The manometric results were also evaluated. RESULTS: Frequencies of fecal incontinence (p = 0.002) and feeling of prolapse (p < 0.001) were significantly higher in the high-grade group. The maximum resting (77.5 vs. 96 mmHg, p = 0.011) and squeezing (128.7 vs. 165 mmHg, p = 0.010) anal pressures were significantly lower in the high-grade group. The frequency of absent or impaired RAIR was significantly higher in the high-grade group (19 cases, 63% vs. 20 cases, 26%, p < 0.001). In a multivariate analysis, the feeling of prolapse (odds ratio [OR], 23.88; 95% confidence interval [CI], 4.43-128.78; p < 0.001) and absent or impaired RAIR (OR, 5.36; 95% CI, 1.91-15.04, p = 0.001) were independent factors of high-grade (III-V) rectal prolapse. In addition, the percentage of the absent or impaired RAIR significantly increased with grading increase of rectal prolapse (p < 0.001). The sensitivity of absent or impaired RAIR as a predictor of high-grade prolapse was 63.3% and specificity 74.0%. CONCLUSIONS: Absent or impaired RAIR was a meaningful diagnostic factor of high-grade (III-V) rectal prolapse. Furthermore, the absent or impaired reflex had a positive linear trend according to the increase of rectal prolapse grading.

Pathophysiological Aspects of Alcohol Metabolism in the Liver.

Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that metabolizes alcohol; therefore, it is particularly sensitive to alcohol intake. Metabolites and byproducts generated during alcohol metabolism cause liver damage, leading to ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, and inducing fibrosis. Despite the severity of ALD, the development of novel treatments has been hampered by the lack of animal models that fully mimic human ALD. To overcome the current limitations of ALD studies and therapy development, it is necessary to understand the molecular mechanisms underlying alcohol-induced liver injury. Hence, to provide insights into the progression of ALD, this review examines previous studies conducted on alcohol metabolism in the liver. There is a particular focus on the occurrence of ALD caused by hepatotoxicity originating from alcohol metabolism.

Anticancer Activity of Continentalic Acid in B-Cell Lymphoma.

Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant's diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.

Simultaneous Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm Combined with Saccular Thoracic Aortic Aneurysm.

With the recent increase in imaging tests, coexisting abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) are being discovered accidentally. We report two cases of simultaneous endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR) for AAA and TAA. Both 74-year-old and 79-year-old male with infrarenal AAA and saccular TAA were treated simultaneously with EVAR and TEVAR. Saccular TAAs were identified in the upper thoracic aorta during the evaluation of AAA. During endograft placement, carotid-subclavian bypass and cerebrospinal fluid (CSF) drainage were performed. Both patients were successfully discharged without spinal cord ischemia. Simultaneous EVAR and TEVAR can be considered for patients with AAA and saccular TAA in the upper thoracic aorta. Moreover, CSF drainage may be necessary to protect the spinal cord.

Successful resolution of gastric perforation caused by a severe complication of pancreatic walled-off necrosis: A case report.

BACKGROUND: Pancreatic walled-off necrosis (WON) rarely causes critical gastric necrosis and perforation, which may develop when pancreatic WON squashes against the stomach. The Atlanta 2012 guidelines were introduced for acute pancreatitis and its related clinical entities. However, there are few reported cases describing the clinical course and resolution of pancreatic WON. CASE SUMMARY: We report the case of a 45-year-old man who presented to the urgent emergency department with gastric perforation caused by a severe complication of pancreatic WON on computed tomography. The patient underwent an emergency distal pancreatectomy, splenectomy, and gastric wedge resection. Postoperative findings showed re-perforation of the gastric wall at a previously resected margin. Furthermore, endoscopic examination revealed an ulcerative area with a defect in the fundus. After diagnostic endoscopy, endoscopic vacuum-assisted closure was performed, and continuous suction was transferred over all tissues in contact with the sponge surface. The patient recovered without any further complications and was discharged in good condition at postoperative week 8. No recurrence occurred during the 6-mo follow-up period. CONCLUSION: When managing a patient with serious gastric perforation complicated by pancreatic WON, a multidisciplinary treatment approach should be considered.

Carbon monoxide enhances early liver regeneration in mice after hepatectomy.

Hepatocyte proliferation early after liver resection is critical in restoring liver mass and preserving function as the liver regenerates. Carbon monoxide (CO) generated by heme oxygenase-1 (HO-1) strongly influences cellular proliferation and both HO-1 and CO are accepted hepatoprotective molecules. Mice lacking functional HO-1 were unable to mount an appropriate regenerative response following partial hepatectomy (PHTx) compared to wildtype controls. We therefore hypothesized that exogenous administration of CO at low, nontoxic concentrations would modulate hepatocyte (HC) proliferation and liver regeneration. Animals treated with a low concentration of CO 1 hour prior to 70% hepatectomy demonstrated enhanced expression of hepatocyte growth factor (HGF) in the liver compared to controls that correlated with a more rapid onset of HC proliferation as measured by phospho-histone3 staining, increased expression of cyclins D1 and E, phosphorylated retinoblastoma, and decreased expression of the mitotic inhibitor p21. PHTx also increased activation of the HGF receptor c-Met, which was detected more then 9 hours earlier in the livers of CO-treated mice. Blockade of c-Met resulted in abrogation of the CO effects on HC proliferation. Corresponding with increased HC proliferation, treatment with CO maintained liver function with normal prothrombin times versus a 2-fold prolongation in controls. In a lethal 85% PHTx, CO-treated mice showed a greater survival rate compared to controls. In vitro, CO increased HGF expression in hepatic stellate cells, but not HC, and when cocultured together led to increased HC proliferation. In summary, we demonstrate that administration of exogenous CO enhances rapid and early HC proliferation and, importantly, preserves function following PHTx. Taken together, CO may offer a viable therapeutic option to facilitate rapid recovery following PHTx.

Clinical usefulness of Mac-2 binding protein glycosylation isomer for diagnosing liver cirrhosis and significant fibrosis in patients with chronic liver disease: A retrospective single-center study.

Accurate diagnosis of liver cirrhosis (LC) and significant fibrosis in patients with chronic liver disease (CLD) is important. The Mac-2 binding protein glycosylation isomer (M2BPGi) has emerged as a novel serum biomarker for liver fibrosis; however, insufficient clinical data of M2BPGi are available in patients with CLD. Therefore, we performed a retrospective cohort study to investigate the clinical usefulness of serum M2BPGi for assessing LC and significant fibrosis in CLD patients. We retrospectively reviewed the CLD patients with measured serum M2BPGi at Kosin University Gospel Hospital between January 2016 and December 2019. Multivariate logistic regression analyses were conducted to identify the independent factors associated with LC. The diagnostic power of serum M2BPGi for LC and significant fibrosis (≥F2) was evaluated and compared to that of other serum biomarkers using receiver operating characteristic curve and area under the curve (AUC). A total of 454 patients enrolled in this study. M2BPGi (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.52-2.07) and fibrosis index based on four factors (aOR, 1.23; 95% CI, 1.11-1.37) were identified as significant independent factors for LC. The AUC of M2BPGi for LC (0.866) and significant fibrosis (0.816) were comparable to those of fibrosis index based on four factors (0.860, 0.773), aspartate aminotransferase-to-platelet ratio index (0.806, 0.752), and gamma-glutamyl transpeptidase-to-platelet ratio (0.759, 0.710). The optimal cut-off values for M2BPGi for LC and significant fibrosis were 1.37 and 0.89, respectively. Serum M2BPGi levels were significantly correlated with liver stiffness measurements (ρ = 0.778). Serum M2BPGi is a reliable noninvasive method for the assessment of LC and significant fibrosis in patients with CLD.

Selected deceased donor liver transplantation in controlled Fournier's gangrene: a case report.

Bacterial infection represents a turning point in the natural history of cirrhosis, causing the development of acute-on-chronic liver failure. It significantly affects the outcome of patients listed for liver transplantation. We report the case of a 57-year-old man who had been regularly treated for hepatitis B virus, alcoholic liver cirrhosis, and hepatic failure. The patient was hospitalized again due to variceal bleeding and hepatic coma. He visited the emergency room with painful anal swelling, dysuria, icteric sclera, and serious abdominal distension. The painful anal swelling and necrosis progressed; thus, he was diagnosed with Fournier's gangrene. Enterococcus faecium and Candida albicans were detected in the blood. Gangrene wound debris was studied extensively. Despite appropriate antibiotic treatment, vancomycin-resistant enterococcus and C. albicans were continuously present in the blood. Wide debridement of the wound and T-colostomy were performed. After this, norepinephrine and vasopressin were used to maintain stable vital signs. It was difficult to establish a liver transplant operation. Despite repeated bleeding, bacterial infections improved with additional antibiotics. Finally, selected deceased donor liver transplantation in controlled Fournier's gangrene was successfully performed. Controlled infections may be allowed in transplantation surgery.

Careful neurologic examination and treatment for intracranial hemorrhage after liver transplantation in patients with alcoholic cirrhosis: case reports.

Intracranial hemorrhage (ICH) following liver transplantation is a potentially devastating complication. Although hypertension and thrombocytopenia are well-known risk factors for ICH in the general population, their roles in ICH after liver transplantation have not been well established. ICH occurred in two patients with alcoholic cirrhosis after deceased donor liver transplantation. A 38-year-old man presented with acute ICH in the right parietal lobe on day 16 after transplantation, with decreased level of consciousness and seizure. His mental status improved with immediate neurological treatment without surgery. In the second case, a 42-year-old woman had acute ICH in the left frontoparietal lobes on day 9 after transplantation, with generalized tonic-clonic seizures. Urgent cerebral decompression was performed. The patient's neurological symptoms gradually recovered. In both cases, the blood platelet count was less than 50,000/mm3. Monitoring cerebral pressure for ICH is an invasive and challenging method, especially in patients with cirrhosis who have issues with hemostasis. Surgeons should be critically mindful of the risk of rapid neurological deterioration in patients with cirrhosis. Careful neurologic examination and immediate treatment to lower intracranial pressure for ICH after liver transplantation in patients with alcoholic cirrhosis are very important.

Mesenchymal Stem Cells Influence Activation of Hepatic Stellate Cells, and Constitute a Promising Therapy for Liver Fibrosis.

Liver fibrosis is a common feature of chronic liver disease. Activated hepatic stellate cells (HSCs) are the main drivers of extracellular matrix accumulation in liver fibrosis. Hence, a strategy for regulating HSC activation is crucial in treating liver fibrosis. Mesenchymal stem cells (MSCs) are multipotent stem cells derived from various post-natal organs. Therapeutic approaches involving MSCs have been studied extensively in various diseases, including liver disease. MSCs modulate hepatic inflammation and fibrosis and/or differentiate into hepatocytes by interacting directly with immune cells, HSCs, and hepatocytes and secreting modulators, thereby contributing to reduced liver fibrosis. Cell-free therapy including MSC-released secretomes and extracellular vesicles has elicited extensive attention because they could overcome MSC transplantation limitations. Herein, we provide basic information on hepatic fibrogenesis and the therapeutic potential of MSCs. We also review findings presenting the effects of MSC itself and MSC-based cell-free treatments in liver fibrosis, focusing on HSC activation. Growing evidence supports the anti-fibrotic function of either MSC itself or MSC modulators, although the mechanism underpinning their effects on liver fibrosis has not been established. Further studies are required to investigate the detailed mechanism explaining their functions to expand MSC therapies using the cell itself and cell-free treatments for liver fibrosis.

Predicting survival time of Korean hepatocellular carcinoma patients using the Cox proportional hazards model: a retrospective study based on big data analysis.

AIM: To predict survival time of Korean hepatocellular carcinoma (HCC) patients by analyzing big data using Cox proportional hazards model. METHODS: Big data of the patients who underwent treatment for HCC from 2008 to 2015, provided by Korea Central Cancer Registry, National Cancer Center, and Ministry of Health and Welfare, were analyzed. A total of 10 742 patients with HCC were divided into two groups, with Group I (3021 patients) confirmed on biopsy and Group II (5563 patients) diagnosed as HCC according to HCC diagnostic criteria as outlined in Korean Liver Cancer Association guidelines. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of recurrence after treatment and survival status. RESULTS: A total of 3021 patients in Group I and 5563 patients in Group II were included in the study and the difference in survival time between the two groups was statistically significant (P < 0.05). Recurrence was only included in intrahepatic cases, and the rates were 21.2 and 19.8% while the periods from the first treatment to recurrence were 15.57 and 14.19 months, respectively. Age, diabetes, BMI, platelet, alpha-fetoprotein, histologic tumor maximum size, imaging T stage, presence of recurrence, and duration of recurrence were included in multivariate analysis. CONCLUSION: By using nationwide, multicenter big data, it is possible to predict recurrence rate and survival time which can provide the basis for treatment response to develop a predictive program.

Alpha-fetoprotein is correlated with intrahepatic recurrence of hepatocellular carcinoma after a hepatectomy.

PURPOSE: Intrahepatic recurrence has a significant effect on the survival of hepatocellular carcinoma (HCC) patients. We aimed to determine if there are useful indicators in predicting the recurrence of liver cancer after a hepatic resection. METHODS: We retrospectively reviewed medical records of 210 HCC patients who underwent hepatectomy between January 2009 and December 2015. We examined clinic-pathological variables comparing 2 groups of HCC patients, either intrahepatic recurrence or not. RESULTS: We divided 184 patients into 2 groups; 94 patients (51.1%) with intrahepatic recurrence and 90 patients (48.9%) without intrahepatic recurrence. Multivariate analysis showed operation type, preoperative α-FP, postoperative protein induced by vitamin K absence-II (PIVKA-II) elevation, and multiple tumor number were closely associated with intrahepatic recurrence. The preoperative PIVKA-II level was not statistically significant in postoperative intrahepatic recurrence rate. The recurrence rate was 46.2% in 132 of 184 cases of α-FP < 100 ng/mL group. Of the 184 cases, α-FP 100-200 ng/mL were 14 cases (12 cases recurred (85.7%)). Alpha-fetoprotein > 200 ng/mL was 38 of 184 cases, 21 of which recurred (55.3%). According to the multivariate analysis, OR ratio was 8.003 (95% confidence interval [CI], 1.549-41.353) in the α-FP 100-200 ng/mL group and 1.867 (95% CI, 0.784-4.444) in α-FP 200 ng/mL or higher group (P = 0.013). Three-year survival rate of intrahepatic recurrence patients was 80.7%, 3-year survival rate of no intrahepatic recurrence patients was 95.0%. CONCLUSION: The intrahepatic recurrence rates were high in the group preop α-FP over 100 ng/mL. Close observation is needed. Prospective study for α-FP genes of HCC patients should be planned for predicting intrahepatic recurrence after hepatectomy.

Relationships between the abnormalities of the male reproductive organs and the accumulation of phenol compounds in the striped field mouse, Apodemus agrarius, inhabiting Korea.

The relationships between the abnormalities of the male reproductive organs in striped field mice and the accumulation of endocrine-disrupting chemicals were assessed. Most mice collected at three areas were contaminated with phenol or organotin compounds. Fourteen to 42% of the mice at each area had abnormally shrunken reproductive organs, and some of them were contaminated with high levels of phenol compounds. Moreover, all the shrunken reproductive organs were damaged in the histological structure. The damage was observed also from several mice accumulating a high level of phenol compounds even though they had normally developed reproductive organs, although no damage was found in the mice accumulating a high level of organotin compounds. Collectively, the abnormalities of the reproductive organs in the mice seemed to be related to the accumulation of phenol compounds rather than of organotin compounds.

Comparative fine structure of the epididymal spermatozoa from three Korean shrews with considerations on their phylogenetic relationships.

This study examined the fine structures of epididymal spermatozoa on the lesser white-toothed shrew (Crocidura suaveolens), the Japanese white-toothed shrew (C. dsinezumi) and the big white-toothed shrew (C. lasiura) belonging to the subfamily Crocidurinae living in Korea. In the spermatozoa of C. suaveolens, the head has a large acrosome, a smooth inner acrosomal membrane and a wavy, finger-like, electron-dense apical body. The neck has a solid proximal centriole that is filled with electron-dense material. These results showed the spermatozoa of C. suaveolens possess the characteristics of both Crocidurinae and Soricinae. In C. dsinezumi and C. lasiura, the head has a large acrosome, a serrated inner acrosomal membrane and a common apical body. The neck has a fistulous proximal centriole with slightly dense electron granules. These results showed the typical characteristics of Crocidurinae. Although C. suaveolens belongs to the subfamily Crocidurinae, the spermatozoan morphology is different from C. dsinezumi and C. lasiurai because it has conserved characteristics of the subfamily Soricinae.

Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis.

PURPOSE: Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer. METHODS: We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression. RESULTS: There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73). CONCLUSION: Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes.

Successful Access Rate and Risk Factor of Vascular Access Surgery in Arm for Dialysis.

PURPOSE: Preservation of adequate vascular access is of vital importance for patients undergoing chronic dialysis in renal failure. The aim of this study is to evaluate the successful access rate and risk factors of arteriovenous fistula (AVF) in the arm for dialysis at a single center. MATERIALS AND METHODS: Patients undergoing vascular access operation between January 2006 and December 2011 were retrospectively identified. RESULTS: A total of 362 vascular access operations were performed. There were 338 autologous AVFs (93.4%) and 24 prosthetic grafts (6.6%). Men comprised 58.3% of all subjects. Mean age was 59.5±14.7 years. There were 187 diabetes mellitus patients (51.7%). There was a mean duration of 70.3±21.1 days between access creation to first cannulation. Overall successful access rate for dialysis was 95.9%. Of 338 autologous AVFs, 326 patients had patent AVFs for dialysis (96.4% surgical success rate), while 21 of 24 prosthetic grafts were patent (87.5% surgical success rate). A total of 141 patients (38.9%) came to surgery with preoperative central venous catheters (CVC) of which 130 (35.9%) AVFs had a patent fistula in the arm. The only risk factor related to successful access rate of AVF was preoperative CVC placement (P=0.012). CONCLUSION: Successful vascular access rate was 95.9%. The only risk factor related to patent access of AVF was preoperative CVC placement. At least 6 months prior to expected dialysis, AVF surgery is recommended, which may overcome the challenge of co-morbid conditions from having a preoperative CVC.

Intrahepatic and extrahepatic intraductal papillary neoplasms of bile duct.

There has been an increase in the number of reported cases of biliary neoplasm of the hepatobiliary system characterized by markedly dilated and multifocal papillary epithelial lesions of the bile ducts or cystic biliary lesions with or without mucin secretion, and mucinous lesions or tumors, possibly due to recent advances in radiological diagnosis. This lesion of the bile duct is believed to show a better clinical course than non-papillary biliary neoplasm. Therefore, the early recognition and treatment is important. We report two cases of intrahepatic and extrahepatic intraductal papillary neoplasm of the bile duct that were completely resected.

Vitamin C modulates lead excretion in rats.

Lead, one of the most toxic heavy metals, takes longer time to be excreted from the body than other heavy metals. The purpose of this study is, by measuring lead excretion via urine and feces, to find out the effect of vitamin C in lead chelation. Thirty-six rats were randomly assorted into four groups. All 33 rats except for the control group were administered with lead, before orally administered with different doses of vitamin C per kilogram of body weight. The lead excretion levels in urine and feces as well as the survival rate were then measured for each group. The rats with lead administrations (10/13, 76.9%) with lead administrations only, 10/11 rats (90.9%) with lead administrations and low dose of vitamin C, 9/9 rats (100%) with lead administrations and high dose of vitamin C survived. Among the 29 surviving rats, low vitamin C intake group exhibited higher urinary excretion than the lead only group. The urinary excretion level in high dose vitamin C intakegroup was significantly higher than the lead only group. In addition, fecal lead excretion seemed to be increased in the high dose vitamin C intake group, compared to the group with lead administrations only with statistical significance. Through animal experiment, it was found out that administrating high dose of vitamin C accelerated the excretion of lead in body compared to low dose of vitamin C.