Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

Totally Laparoscopic Distal Gastrectomy in Post Liver Transplant Patient

The risk of malignancy after transplantation is higher than that of general population. Laparoscopic surgery has become a standard treatment of gastric cancer. However, there are no case reports evaluating totally laparoscopic gastrectomy in patients with previous liver transplantation. Herein we report our experience with a liver transplant recipient who underwent totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. A 63 year-old man underwent orthotopic liver transplantation (OLT) for cryptogenic liver cirrhosis. 8 years later, gastric cancer was diagnosed during the follow-up. Endoscopic submucosal dissection was performed and additional surgical resection was needed. TLDG and D1+ lymph node dissection was performed, and the patient was discharged on the 8th post-operative day without any complications. To the best of our knowledge, this is the first case of de novo gastric cancer treated with TLDG after OLT. This suggests that TLDG is a feasible for patients after OLT.

Inhibition of HIF1α and PDK Induces Cell Death of Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.

Effect of Single and Double Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Focal Cerebral Ischemia in Rats

Stem cell therapies are administered during the acute phase of stroke to preserve the penumbral tissues from ischemic injury. However, the effect of repeated cell therapy during the acute phase remains unclear. In this study, we investigated and compared the functional outcome of single (two days post-injury) and repeated (two and nine days post-injury) treatment with human umbilical cord derived mesenchymal stem cells (hUCB-MSCs) after middle cerebral artery occlusion (MCAO). The rotarod and limb placement tests were utilized to investigate functional outcomes, while infarct volume and tissue damage were measured by immunofluorescent staining for neovascularization, neurogenesis, apoptosis, and inflammation in the penumbral zones. We observed notable motor dysfunction and a significant decrease in infarcted brain volume, as well as increases in neurons and vessels in both single and repeated hUCB-MSC treatments compared to the control group. Interestingly, repeated administration of hUCB-MSCs was not found to elicit additional or synergistic improvements over monotherapy. This study suggests that a clearer understanding of the therapeutic window after stroke will facilitate the development of more efficient treatment protocols in the clinical application of stem cell therapy.

Behavior, PET and Histology in Novel Regimen of MPTP Marmoset Model of Parkinson's Disease for Long-Term Stem Cell Therapy

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.

Posttransplant Diabetes Mellitus after Liver Transplantation: Risk Factors for Persistence / 대한이식학회지

BACKGROUND: The leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Diabetes mellitus (DM) is one of the greatest contributing factors to these late events, but also one of the most modifiable. This study was conducted to identify the incidence and time course of posttransplant diabetes mellitus (PTDM) after liver transplantation (LT) and evaluate the factors related to the development and reversal of PTDM. METHODS: Patients who underwent LT between 2002 and 2015 at Ulsan University Hospital, were followed for more than 3 months and had no history of preoperative DM were the subject of this study. The authors investigated the incidence and time course of PTDM. Recipient factors, donor factors and postoperative factors presumed to contribute to the development and reversal of PTDM were investigated. Moreover, the effects of PTDM on the survival of liver transplant recipients were also investigated. RESULTS: PTDM developed in 13 (16.5%) of 79 patients who fulfilled the inclusion criteria a median of 35 days after LT. There were no significant factors contributing to the development of PTDM. Five of the 13 PTDM patients recovered from the diabetic condition 5 to 38 months after the diagnosis of PTDM. Higher postoperative magnesium levels (P=0.022), development of acute cellular rejection (P=0.01), and steroid pulse therapy (P=0.045) were the predictive factors for reversal of PTDM. PTDM had no impact on patient survival (P=0.529). CONCLUSIONS: PTDM usually developed soon after LT operation and was reversible in 41% of the cases, especially when it is associated with steroid pulse therapy for acute cellular rejection. The association between serum magnesium level and reversibility of PTDM after LT needs further study to clarify the cause-and-effect relationship.

The Unreliability of MTT Assay in the Cytotoxic Test of Primary Cultured Glioblastoma Cells

MTT assay is commonly used to assess the cellular cytotoxicity caused by anticancer drugs in glioblastomas. However, there have been some reports insisting that MTT assay exhibited non-specific intracellular reduction of tetrazolium which led to underestimated results of cytotoxicity. Here, we examine whether or not MTT assay can lead to incorrect information regarding alcohol-induced cytotoxicity on immortalized and primary glioblastoma cells. MTT assay was applied to assess the ethanol-induced cytotoxicity at various ethanol concentrations. The cellular cytotoxicity induced by different doses of ethanol was analyzed and compared through several cytotoxic assays. Ethanol-induced cytotoxicity observed through MTT assay on both cell types was shown to be ethanol dose-dependent below a 3% concentration. However, the cytotoxicity was shown to be markedly underestimated only in primary cells at a 5% concentration. RT-PCR and Western Blot showed increased expressions of pro-apoptotic proteins and decreased expressions of anti-apoptotic proteins in an ethanol dose-dependent manner in both cell types. Furthermore, we present a possible mechanism for the unreliable result of MTT assay. A high concentration of ethanol induces more severe membrane damage and increased intracellular concentration of NADH in primary cells which enhances the nonspecific reduction of tetrazolium salt. Together, our findings demonstrate that the cytotoxicity on primary cells could inaccurately be assessed when detected through MTT assay. Therefore, a careful interpretation is needed when one would analyze the cytotoxic results of MTT assay, and it is suggested that other assays must be accompanied to produce more reliable and accurate cytotoxic results on primary glioblastoma cells.

The Effect of Donor-Dependent Administration of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells following Focal Cerebral Ischemia in Rats

Stroke is an ischemic disease caused by clotted vessel-induced cell damage. It is characterized by high morbidity and mortality and is typically treated with a tissue plasminogen activator (tPA). However, this therapy is limited by temporal constraints. Recently, several studies have focused on cell therapy as an alternative treatment. Most researches have used fixed donor cell administration, and hence, the effect of donor-dependent cell administration is unknown. In this study, we administered 3 types of donor-derived human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in the ischemic boundary zone of the ischemic stroke rat model. We then performed functional and pathological characterization using rotarod, the limb placement test, and immunofluorescent staining. We observed a significant decrease in neuron number, and notable stroke-like motor dysfunction, as assessed by the rotarod test (~40% decrease in time) and the limb placement test (4.5 point increase) in control rats with ischemic stroke. The neurobehavioral performance of the rats with ischemic stroke that were treated with hUCB-MSCs was significantly better than that of rats in the vehicle-injected control group. Regardless of which donor cells were used, hUCB-MSC transplantation resulted in an accumulation of neuronal progenitor cells, and angiogenic and tissue repair factors in the ischemic boundary zone. The neurogenic and angiogenic profiles of the 3 types of hUCB-MSCs were very similar. Our results suggest that intraparenchymal administration of hUCB-MSCs results in significant therapeutic effects in the ischemic brain regardless of the type of donor.

COMP-Ang1 Potentiates EPC Treatment of Ischemic Brain Injury by Enhancing Angiogenesis Through Activating AKT-mTOR Pathway and Promoting Vascular Migration Through Activating Tie2-FAK Pathway

Successful recovery from brain ischemia is limited due to poor vascularization surrounding the ischemic zone. Cell therapy with strong angiogenic factors could be an effective strategy to rescue the ischemic brain. We investigated whether cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable and potent Ang1 variant, enhances the angiogenesis of human cord blood derived endothelial progenitor cells (hCB-EPCs) for rescuing brain from ischemic injury. COMP-Ang1 markedly improved the tube formation of capillaries by EPCs and incorporation of EPCs into tube formation with human umbilical vein endothelial cells (HUVECs) upon incubation on matrigel in vitro. COMP-Ang1 stimulated the migration of EPCs more than HUVECs in a scratch wound migration assay. The transplanted EPCs and COMP-Ang1 were incorporated into the blood vessels and decreased the infarct volume in the rat ischemic brain. Molecular studies revealed that COMP-Ang1 induced an interaction between Tie2 and FAK, but AKT was separated from the Tie2-FAK-AKT complex in the EPC plasma membrane. Tie2-FAK increased pp38, pSAPK/JNK, and pERK-mediated MAPK activation and interacted with integrins alphanubeta3, alpha4, beta1, finally leading to migration of EPCs. AKT recruited mTOR, SDF-1, and HIF-1alpha to induce angiogenesis. Taken together, it is concluded that COMP-Ang1 potentiates the angiogenesis of EPCs and enhances the vascular morphogenesis indicating that combination of EPCs with COMP-Ang1 may be a potentially effective regimen for ischemic brain injury salvage therapy.

The Effect of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a Collagenase-Induced Intracerebral Hemorrhage Rat Model

Intracerebral hemorrhage (ICH) is one of the devastating types of stroke. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have potential benefits in recovery from brain damage following ICH. This study aimed to identify the beneficial effects of hUCB-MSCs and investigate whether they have anti-inflammatory effects on the ICH brain via neurotrophic factors or cytokines. hUCB-MSCs were transplanted into a collagenase-induced ICH rat model. At 2, 9, 16, and 30 days after ICH, rotarod and limb placement tests were performed to measure behavioral outcomes. ICH rats were sacrificed to evaluate the volume of lesion using H&E staining. Immunostaining was performed to investigate neurogenesis, angiogenesis, and anti-apoptosis at 4 weeks after transplantation. Inflammatory factors (TNF-alpha, COX-2, microglia, and neutrophils) were analyzed by immunofluorescence staining, RT-PCR, and Western blot at 3 days after transplantation. hUCB-MSCs were associated with neurological benefits and reduction in lesion volume. The hUCB-MSCs-treated group tended to reveal high levels of neurogenesis, angiogenesis, and anti-apoptosis (significant for angiogenesis). The expression levels of inflammatory factors tended to be reduced in the hUCB-MSCs-treated group compared with the controls. Our study suggests that hUCB-MSCs may improve neurological outcomes and modulate inflammation-associated immune cells and cytokines in ICH-induced inflammatory responses.

Fully Implantable Deep Brain Stimulation System with Wireless Power Transmission for Long-term Use in Rodent Models of Parkinson's Disease

OBJECTIVE: The purpose of this study to develop new deep-brain stimulation system for long-term use in animals, in order to develop a variety of neural prostheses. METHODS: Our system has two distinguished features, which are the fully implanted system having wearable wireless power transfer and ability to change the parameter of stimulus parameter. It is useful for obtaining a variety of data from a long-term experiment. RESULTS: To validate our system, we performed pre-clinical test in Parkinson's disease-rat models for 4 weeks. Through the in vivo test, we observed the possibility of not only long-term implantation and stability, but also free movement of animals. We confirmed that the electrical stimulation neither caused any side effect nor damaged the electrodes. CONCLUSION: We proved possibility of our system to conduct the long-term pre-clinical test in variety of parameter, which is available for development of neural prostheses.

A comparative study regarding the effect of an intraperitoneal anti-adhesive agent application in left-liver living donors

BACKGROUNDS/AIMS: After left-sided hepatectomy due to a living donor, the stomach can become adhered to the hepatic cut surface. An unwanted gastric stasis can occur. For prevention of such gastric adhesion and laparotomy-associated adhesive ileus, some anti-adhesive agents have been developed for intra-abdominal application. The purpose of this study is to evaluate the effect of an intraperitoneal anti-adhesive agent application compared with a historical control group. METHODS: The study group consisted of 220 consecutive living donors who donated a left-liver graft during the time period between January 2006 and December 2011. The anti-adhesive agent which was used was composed of sodium hyaluronate and sodium carboxymethyl cellulose. The historical control group which used no anti-adhesive agent included 220 consecutive left-liver donors during the time period between January 1998 and December 2004. RESULTS: An overt gastric stasis which required fasting was observed in 5 subjects (2.3%) in the study group and in 7 subjects (3.2%) in the control group (p=0.77). An additional work-up to determine gastric stasis or prolonged ileus was performed in 17 (7.7%) and 22 (10%) donors, respectively (p=0.51). Only one donor in the control group underwent a laparotomy for an intestinal obstruction. No clinical factors such as patient age, sex, body mass index, remnant right liver proportion, shape of skin incision, and duration of surgery were significant risk factors of gastric stasis or prolonged ileus. No harmful side-effects of the anti-adhesive agent were identified. CONCLUSIONS: As a result of this study, the application of an anti-adhesive agent could not be proved as to be effective for prevention of gastric stasis and postoperative ileus. A further randomized and controlled study will be required to demonstrate the real benefits of an anti-adhesive application in left-liver living donors.

Synchronous Malignant Intraductal Papillary Mucinous Neoplasms of the Bile Duct and Pancreas Requiring Left Hepatectomy and Total Pancreatectomy / 대한소화기학회지

Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) and intraductal papillary mucinous neoplasm of the pancreas (IPMN-P) have striking similarities and are recognized as counterparts. However, simultaneous occurrence of IPMN-B and IPMN-P is extremely rare. A 66 year-old female presented with recurrent epigastric pain and fever. During the past 9 years, she had three clinical episodes related to intrahepatic duct stones and IPMN-P in the pancreas head and was managed by medical treatment. Laboratory test results at admission revealed leukocytosis (12,600/mm3) and elevated CA 19-9 level (1,200 U/mL). Imaging study demonstrated liver abscess in the Couinaud's segment 4, IPMN-B in the left lobe, and IPMN-P in the whole pancreas with suspicious malignant change. Liver abscess was drained preoperatively, followed by left lobectomy with bile duct resection and total pancreatectomy with splenectomy. On histologic examination, non-invasive intraductal papillary mucinous carcinoma arising from various degree of dysplastic mucosa of the liver and pancreas could be observed. However, there was no continuity between the hepatic and pancreatic lesions. This finding in our case supports the theory that double primary lesions are more likely explained by a diffuse IPMN leading to synchronous tumors arising from both biliary and pancreatic ducts rather than by a metastatic process. Herein we present a case of simultaneous IPMN of the bile duct and pancreas which was successfully treated by surgical management.

Proposed Motor Scoring System in a Porcine Model of Parkinson's Disease induced by Chronic Subcutaneous Injection of MPTP

Destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is a common pathophysiology of Parkinson's disease (PD). Characteristics of PD patients include bradykinesia, muscle rigidity, tremor at rest and disturbances in balance. For about four decades, PD animal models have been produced by toxin-induced or gene-modified techniques. However, in mice, none of the gene-modified models showed all 4 major criteria of PD. Moreover, distinguishing between PD model pigs and normal pigs has not been well established. Therefore, we planned to produce a pig model for PD by chronic subcutaneous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), neurotoxin. Changes in behavioral patterns of pigs were thoroughly evaluated and a new motor scoring system was established for this porcine model that was based on the Unified Parkinson's Disease Rating Scale (UPDRS) in human PD patients. In summary, this motor scoring system could be helpful to analyze the porcine PD model and to confirm the pathology prior to further examinations, such as positron emission tomography-computed tomography (PET-CT), which is expensive, and invasive immunohistochemistry (IHC) of the brain.

Mitochondrial Dysfunction of Immortalized Human Adipose Tissue-Derived Mesenchymal Stromal Cells from Patients with Parkinson's Disease

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Living donor liver transplantation for patients with alcoholic liver disease

BACKGROUNDS/AIMS: Since most transplantation studies for alcoholic liver disease (ALD) were performed on deceased donor liver transplantation, little was known following living donor liver transplantation (LDLT). METHODS: The clinical outcome of 18 ALD patients who underwent LDLT from Febraury 1997 to December 2004 in a large-volume liver transplantation center was assessed retrospectively. RESULTS: The model for end-stage liver disease score was 23+/-11, and mean pretransplant abstinence period was 16+/-13 months, with 14 (77.8%) patients being abstinent for at least 6 months. Graft types were right lobe grafts in 11, left lobe grafts in 2 and dual grafts in 5. Graft to recipient body weight ratio was 0.94+/-0.16. The relapse rates in patients who did and did not maintain 6 months of abstinence were 7.1% and 50%, respectively (p=0.097). Younger recipient age was a significant risk factor for alcohol relapse (p=0.027). Five recipients with antibody to hepatitis B surface antigen (HBsAg) received core antibody-positive liver graft, but two of them showed positive HBsAg seroconversion. Overall 5-year patient survival rate following LDLT was 87.8%, with a 5-year relapse rate of 16.7%. CONCLUSIONS: Pretransplant abstinence for 6 months appears to be benefical for preventing posttransplant relapse. Life-long prophylactic measure should be followed after use of anti-HBc-positive liver grafts regardless of hepatitis B viral marker status of the recipient.

Effectiveness of external drainage of the bile duct in pancreaticoduodenectomy: a single surgeon's experience

BACKGROUNDS/AIMS: The rates of surgery-related complications during and after pancreaticoduodenectomy (PD) remain very high, reaching up to 41%. They were primarily caused by leakage of pancreatic juice. We evaluated the effectiveness of external drainage of the bile duct using a pigtail drain to prevent pancreatic leakage in patients undergoing PD. METHODS: We evaluated 79 patients who underwent PD using a single-layer continuous suture between the pancreatic parenchyma and jejunum after duct-to-mucosa anastomosis by a single surgeon from April 2005 to December 2008. Of the 79, 44 underwent external drainage (ED) of the bile duct using a pigtail drain, performed in the intraoperative field via a retrograde transhepatic approach, whereas 35 did not undergo ED. RESULTS: Age, sex distribution, number of total complications, pancreatic duct size, pancreatic texture and duration of hospital stay did not differ between patients who did and did not undergo ED. In groups with or without ED, 0 and 4 patients, respectively, showed leakage of pancreatic juice and the difference was statistically significant (p=0.02). CONCLUSIONS: The fact that none of the patients who underwent external drainage experienced pancreatic leakage, suggests that external drainage of the bile duct with a pigtail drain to decompress the jejunum and to drain pancreatic and bile juice is useful in preventing the complications of pancreatic leakage.

Performance Enhancement with Low Stress and Anxiety Modulated by Cognitive Flexibility

OBJECTIVE: The purpose of this study was to compare cognitive flexibility abilities, stress, and anxiety between starters and non-starter athletes. METHODS: A total of 30 male professional-soccer and 40 professional-baseball athletes were recruited. Wisconsin Card Sorting Test (WCST) and Trail Making Test A & B (TMT A & B) were administered to assess cognitive flexibility during competition. The Korean version of the STAI form Y (STAI-KY) and Visual analogue scale for anxiety and stress were used to assess the anxiety and stress. RESULTS: The starter group had better cognitive function (fewer perseverative errors and rapid TMTB times) (Z=3.32, p<0.01; Z=2.20, p=0.03, respectively) and lower stress and anxiety (F=4.34, p=0.01; F=6.61, p<0.01, respectively) during competition than the non-starter group. CONCLUSION: The better cognitive performances were negatively correlated with stress and anxiety. Current results suggested that cognitive flexibility would enhance human performance by modulation of the anxiety and stress during competition.

Pediatric Pancreatic Tumors-Clinical Experience

Pancreatic tumors in children are relatively rare, and their prognosis differs from that in adults. The purpose of this study is to examine the clinical characteristics, treatment, and prognosis for children with pancreatic tumors. We retrospectively reviewed the medical records of children under 15 years of age with pancreatic tumors who were treated surgically at Asan Medical Center between January 1992 and November 2009. There were 16 patients, fourteen of whom were pathologically diagnosed with solid pseudopapillary tumor. The other two patients were diagnosed with pancreatoblastoma and acinar cell carcinoma, respectively. Six patients of the 16 patients (38%) were male, and there was a male-to-female ratio of 1:1.6. The initial presentations were upper abdominal pain in eight patients (50%), palpable abdominal mass in three, and vomiting in one. Four patients were diagnosed incidentally. Six patients' tumors were located in the pancreatic head, six in the pancreatic body, and four in the pancreatic tail, respectively. The surgical procedures performed included distal pancreatectomy (n=7, 44%), median segmentectomy (n=3), enucleation (n=3), pancreaticoduodenectomy (n=2), and pylorus-preserving pancreaticoduodenectomy (n=1). Three patients underwent laparoscopic surgery. The median tumor size was 6.5cm (1.8~20 cm). Early surgical complications included pancreatic fistula (n=4), bile leakage (n=1), and delayed gastric emptying (n=1). A late complication in one patient was diabetes. The median follow-up period was five years and four months, and all patients survived without recurrence. While pancreatic tumors in adults have a poor prognosis, pancreatic tumors of childhood are usually curative with complete resection and thus have a favorable prognosis.