Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. Conclusion The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

Purpose: Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. This retrospective, single-center study evaluated the outcomes of hepatic resection (HR) in patients with hepatic EHE. Methods: Over the 10-year period from 2009 to 2018, 11 patients with hepatic EHE underwent HR, accounting for 0.1% of the 11,979 adults who underwent HR at our center. Diagnosis of hepatic EHE was confirmed by immunohistochemical staining for CD34, CD31, and factor VIII-related antigen. Results: The 11 patients included 9 females (81.8%) and 2 males (18.2%) with mean age of 43.5 ± 13.6 years. Preoperative imaging resulted in a preliminary diagnosis of suspected liver metastasis or EHE, with 9 patients (81.8%) undergoing liver biopsy. No patient presented with abnormally elevated concentrations of liver tumor markers. The extents of HR were determined by tumor size and location from trisectionectomy to partial hepatectomy. All patients recovered uneventfully from HR. Five patients showed tumor recurrence, with 4 receiving locoregional treatments for recurrent lesions. The 1-, 3-and 5-year disease-free survival rates were 90.9%, 54.5%, and 54.5%, respectively. Currently, all patients remain alive and are doing well. Univariate analysis on tumor recurrence showed that tumor size ≥ 4 cm was significantly associated with tumor recurrence (P = 0.032), but tumor number ≥ 4 was not related to (P = 0.24). Conclusion Hepatic EHE is a rare form of primary liver tumor often misdiagnosed as a metastatic tumor. Because of its malignant potential, HR is indicated if possible. HR plus, when necessary, treatment of recurrence yields favorable overall survival rates in patients with hepatic EHE.

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. Conclusion The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

Background: Split liver transplantation (SLT) has been occasionally performed in Korea. This study compared the incidence and prognosis of SLT with whole liver transplantation (WLT) in adult patients. Methods: Between June 2016 and November 2019, 242 adult patients underwent a total of 256 deceased donor liver transplantation operations. SLT was performed in 7 patients (2.9%). Results: The mean age of SLT donors was 29.7 ± 7.4 years, and the mean age of recipients was 55.7 ± 10.6 years, with the latter having a mean model for end-stage liver disease score of 34.6 ± 3.1. Mean split right liver graft weight was 1,228.6 ± 149.7 g and mean graft-recipient weight ratio was 1.97 ± 0.39. Of the seven SLT recipients, Korean Network for Organ Sharing (KONOS) status was one in status 1, one in status 2 and five in status 3. The graft (p = 0.72) and patient (p = 0.84) survival rates were comparable in the SLT and WLT groups. Following propensity score matching, graft (p = 0.61) and patient (p = 0.91) survival rates remained comparable in the two groups. Univariate analysis showed that pretransplant ventilator support and renal replacement therapy were significantly associated with patient survival, whereas KONOS status category and primary liver diseases were not. Multivariate analysis showed that pretransplant ventilator support was an independent risk factor for patient survival. Conclusion Survival outcomes were similar in adult SLT and WLT recipients, probably due to selection of high-quality grafts and low-risk recipients. Prudent selection of donors and adult recipients for SLT may expand the liver graft pool for pediatric patients without affecting outcomes in adults undergoing SLT.

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

Stem cell technologies are particularly attractive in Parkinson's disease (PD) research although they occasionally need long-term treatment for anti-parkinsonian activity. Unfortunately, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) widely used as a model for PD has several limitations, including the risk of dose-dependent mortality and the difficulty of maintenance of PD symptoms during the whole experiment period. Therefore, we tested if our novel MPTP regimen protocol (2 mg/kg for 2 consecutive days and 1 mg/kg for next 3 consecutive days) can be maintained stable parkinsonism without mortality for long-term stem cell therapy. For this, we used small-bodied common marmoset monkeys (Callithrix jacchus) among several nonhuman primates showing high anatomical, functional, and behavioral similarities to humans. Along with no mortality, the behavioral changes involved in PD symptoms were maintained for 32 weeks. Also, the loss of jumping ability of the MPTP-treated marmosets in the Tower test was not recovered by 32 weeks. Positron emission tomography (PET) analysis revealed that remarkable decreases of bindings of ¹⁸F-FP-CIT were observed at the striatum of the brains of the marmosets received MPTP during the full period of the experiment for 32 weeks. In the substantia nigra of the marmosets, the loss of tyrosine hydroxylase (TH) immunoreactivity was also observed at 32 weeks following the MPTP treatment. In conclusion, our low-dose MPTP regimen protocol was found to be stable parkinsonism without mortality as evidenced by behavior, PET, and TH immunohistochemistry. This result will be useful for evaluation of possible long-term stem cell therapy for anti-parkinsonian activity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Brain ; Callithrix* ; Haplorhini ; Humans ; Immunohistochemistry ; Models, Animal ; Mortality ; Parkinson Disease* ; Parkinsonian Disorders ; Positron-Emission Tomography ; Primates ; Stem Cells* ; Substantia Nigra ; Tyrosine 3-Monooxygenase

Nonhuman primates (NHPs) have been widely used in reproductive biology, neuroscience, and drug development since a number of primate species are phylogenetically close to humans. In this review, we summarize the use of NHPs for nonclinical application in the reproductive system disorders including the loss or failure of an organ or tissue. Causes of infertility include congenital aplasia and acquired disorders of the reproductive organs. In addition, anti-cancer treatments can deplete ovarian follicles, leading to premature ovarian failure, infertility and long-term health risks. Along with a limited supply of human reproductive organs, anatomic/physiologic similarities to humans support the need for NHP models (New-World monkeys such as the common marmoset and Old-World monkeys such as cynomolgus and rhesus monkeys) to promote the advances in female infertility studies. For maintaining and executing animal studies using NHP, special protocols including animal care, anesthetic protocol, surgical technique, and immunosuppressive protocol are necessary. With a growing interest in the potential therapies such as endometrial tissue engineering, and ovary/follicle cryopreservation and grafting in Korea, this review can be useful in selecting appropriate animal models and can bridge between nonclinical studies and clinical applications by providing detailed information on the use of NHPs in the field of reproductive organ disorders.
Animals ; Biology ; Callithrix ; Cryopreservation ; Female* ; Haplorhini ; Humans ; Infertility ; Infertility, Female ; Korea ; Models, Animal ; Neurosciences ; Ovarian Follicle ; Primary Ovarian Insufficiency ; Primates* ; Tissue Engineering ; Transplantation ; Transplants

BACKGROUND: Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. OBJECTIVE: Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. METHODS: Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. RESULTS: Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. CONCLUSION: Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment.
Desonide ; Diffusion ; Epidermis ; Glucocorticoids ; Inflammation ; Permeability ; Retention (Psychology) ; Skin ; Steroids

Adult ; Animals ; Bone Regeneration ; Calcium Phosphates ; Female ; Fibrin ; Fibroins ; Foreign-Body Reaction ; Humans ; Inflammation ; Membranes ; Rats ; Silk ; Skull ; Tissue Engineering ; Transplants