Potentiation of the Anticancer Effects by Combining Docetaxel with Ku-0063794 against Triple-Negative Breast Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#mTORC1 and mTORC2 inhibition by Ku-0063794 could confer profound anticancer effects against cancer cells because it eliminates feedback activation of Akt. Herein, we aimed to determine anticancer effects of docetaxel and Ku-0063794, individually or in combination, against breast cancer cells, especially triple-negative breast cancer (TNBC) cells. @*Materials and Methods@#MCF-7 breast cancer and MDA-MB-231 TNBC cell lines for in vitro studies and mouse xenograft model for in vivo studies were used to investigate the effect of docetaxel, Ku-0063794, or their combination. @*Results@#In the in vitro experiments, combination therapy synergistically reduced cell viability and induced higher apoptotic cell death in breast cancer cells than the individual monotherapies (p < 0.05). Western blot analysis and flow cytometric analysis showed that the combination therapy induced higher apoptotic cell death than the individual monotherapies (p < 0.05). In the in vivo experiment, docetaxel and Ku-0063794 combination therapy reduced the growth of MDA-MB-231 cells xenografted in the nude mice better than in the individual monotherapies (p < 0.05). Immunohistochemistry showed that the combination therapy induced the highest expression of cleaved caspase-3 and the lowest expression of Bcl-xL in the MDA-MB-231 cells xenografted in the nude mice (p < 0.05). Western blot analysis and immunofluorescence, incorporating both in vitro and in vivo experiments, consistently validated that unlike individual monotherapies, docetaxel and Ku-0063794 combination therapy significantly inhibited epithelial-mesenchymal transition (EMT) and autophagy (p < 0.05). @*Conclusion@#These data suggest that docetaxel and Ku-0063794 combination therapy has higher anticancer activities over individual monotherapies against MDA-MB-231 TNBC cells through a greater inhibition of autophagy and EMT.

A novel strategy to promote liver regeneration: utilization of secretome obtained from survivin-overexpressing adipose-derived stem cells

Purpose@#Survivin is a typical antiapoptotic protein. It is copiously expressed during human fetal development but is infrequently present in adult tissues. In this experiment, we researched the treatment effect of the secretome that adiposederived stem cells (ASCs) transfected with survivin. @*Methods@#First of all, we generated survivin-overexpressing ASCs transfected with a plasmid comprising a gene encoding survivin. The secreted substances released from survivin-overexpressing ASCs (survivin-secretome) were collected, and were determined their in vitro and in vivo therapeutic potential, especially in the model of liver impairment. @*Results@#In vitro, the survivin-secretome significantly increased cell viability and promoted the expression of proliferationrelated markers (proliferating cell nuclear antigen [PCNA], phospho-signal transducer and activator of transcription 3 (p-STAT3), hepatocyte growth factor [HGF], vascular endothelial growth factor [VEGF]) and anti-apoptosis-related markers (myeloid cell leukemia-1 [Mcl-1] and survivin) (P < 0.05). In vivo using 70% hepatectomy mice, the survivin-secretome group exhibited the lowest serum levels of interleukin-6, tumor necrosis factor-α (P < 0.05). The serum levels of liver transaminases (alanine aminotransferase and aspartate aminotransferase) were also the lowest in the survivin-secretome group (P < 0.05). The survivin-secretome group also exhibited the highest liver regeneration on the 7th day after 70% partial hepatectomy (P < 0.05). In the subsequent liver specimen analysis, the specimens of survivin-secretome exhibited the highest expression of p-STAT3, HGF, VEGF, PCNA, and Mcl-1 and the lowest expression of bcl-2-like protein 4 (P < 0.05). @*Conclusion@#Taken together, secretome secreted by survivin-overexpressing ASCs could be an effective way to improve liver regeneration and repair for liver injury treatment.

Serum level of visfatin can reflect the severity of inflammation in patients with acute cholecystitis

Purpose@#Visfatin is a key cytokine released from the pe ripheral blood mononuclear cells (PBMCs) as well as adipose tissue, and it is involved in immune response as well as inflammation. In this study, we investigated whether the serum visfatin level could be a prognostic factor for predicting the severity of inflammation in patients with acute cholecystitis. @*Methods@#We examined the blood samples and gallbladder specimens from patients who underwent laparoscopic cholecystectomy for either acute (n = 18) or chronic cholecystitis (n = 18). We determined the visfatin levels of these samples using various procedures such as real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. @*Results@#The patients with acute cholecystitis exhibited higher mRNA expression of visfatin in PBMCs, higher serum levels of visfatin, and increased protein expression of visfatin in the gallbladder specimens than in patients with chronic cholecystitis. In the in vitro model of acute cholecystitis, the mRNA expression of visfatin showed the fastest increase among the other pro-inflammatory mediators studied, including interleukin (IL)-10, tumor necrosis factor-, IL-6, intracellular adhesion molecule-1, and ascular cell adhesion molecule-1. Inhibition of visfatin using siRNA abrogated the inhibitory effects of lipopolysaccharide (LPS) on the expression of ABCG1 in GBECs, suggesting that visfatin is significantly involved in the LPS-driven suppression of ABCG1. @*Conclusion@#Taken together, we concluded that visfatin is a pro-inflammatory mediators that is upregulated during acute cholecystitis and is expected to be increased within a short time after inflammation. Therefore, measuring the serum level of visfatin would be helpful in predicting the inflammatory severity in the patients with acute cholecystitis.

Serum level of visfatin can reflect the severity of inflammation in patients with acute cholecystitis

Purpose@#Visfatin is a key cytokine released from the pe ripheral blood mononuclear cells (PBMCs) as well as adipose tissue, and it is involved in immune response as well as inflammation. In this study, we investigated whether the serum visfatin level could be a prognostic factor for predicting the severity of inflammation in patients with acute cholecystitis. @*Methods@#We examined the blood samples and gallbladder specimens from patients who underwent laparoscopic cholecystectomy for either acute (n = 18) or chronic cholecystitis (n = 18). We determined the visfatin levels of these samples using various procedures such as real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. @*Results@#The patients with acute cholecystitis exhibited higher mRNA expression of visfatin in PBMCs, higher serum levels of visfatin, and increased protein expression of visfatin in the gallbladder specimens than in patients with chronic cholecystitis. In the in vitro model of acute cholecystitis, the mRNA expression of visfatin showed the fastest increase among the other pro-inflammatory mediators studied, including interleukin (IL)-10, tumor necrosis factor-, IL-6, intracellular adhesion molecule-1, and ascular cell adhesion molecule-1. Inhibition of visfatin using siRNA abrogated the inhibitory effects of lipopolysaccharide (LPS) on the expression of ABCG1 in GBECs, suggesting that visfatin is significantly involved in the LPS-driven suppression of ABCG1. @*Conclusion@#Taken together, we concluded that visfatin is a pro-inflammatory mediators that is upregulated during acute cholecystitis and is expected to be increased within a short time after inflammation. Therefore, measuring the serum level of visfatin would be helpful in predicting the inflammatory severity in the patients with acute cholecystitis.

Antioxidant action of hypoxic conditioned media from adipose-derived stem cells in the hepatic injury of expressing higher reactive oxygen species

PURPOSE: Almost all liver diseases are known to be accompanied by increased levels of reactive oxygen species (ROS), regardless of the cause of the liver disorder. However, little is known about the role of hypoxic conditioned media (HCM) in the view of pro-oxidative/antioxidative balance. METHODS: Normoxic conditioned media (NCM) and HCM were obtained after culturing adipose-derived stem cells in 20% O₂ or 1% O₂ for 24 hours, respectively. Their effects on the expression of various markers reflecting pro-oxidative/antioxidative balance were investigated in both in vitro (thioacetamide-treated AML12 cells) and in vivo (partially hepatectomized mice) models of liver injury, respectively. RESULTS: HCM treatment induced the higher expression of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase than did NCM in the in vitro model of liver injury. We also found that HCM increased the expression of nuclear factor erythroid 2-related factor (NRF2). The in vivo models of liver injury consistently validated the phenomenon of upregulated expression of antioxidant enzymes by HCM. CONCLUSION: We thus could conclude that HCM provides protection against ROS-related toxicity by increasing the expression of antioxidant enzymes, in part by releasing NRF2 in the injured liver.

Isolation of Secretome with Enhanced Antifibrotic Properties from miR-214-Transfected Adipose-Derived Stem Cells

BACKGROUND: Secretome refers to the total set of molecules secreted or surface-shed by stem cells. The limitations of stem cell research have led numerous investigators to turn their attention to the use of secretome instead of stem cells. In this study, we intended to reinforce antifibrotic properties of the secretome released from adipose-derived stem cells (ASCs) transfected with miR-214. METHODS: We generated miR-214-transfected ASCs, and extracted the secretome (miR214-secretome) from conditioned media of the transfected ASCs through a series of ultrafiltrations. Subsequently, we intravenously injected the miR-214-secretome into mice with liver fibrosis, and determined the effects of miR-214-secretome on liver fibrosis. RESULTS: Compared with that by naïve secretome, liver fibrosis was ameliorated by intravenous infusion of miR-214-secretome into mice with liver fibrosis, which was demonstrated by significantly lower expression of fibrosis-related markers (alpha-smooth muscle actin, transforming growth factor-β, and metalloproteinases-2) in the livers as well as lower fibrotic scores in the special stained livers compared with naïve secretome. The infusion of miR-214-secretome also led to lesser local and systemic inflammation, higher expression of an antioxidant enzyme (superoxide dismutase), and higher liver proliferative and synthetic function. CONCLUSION: MicroRNA-214 transfection stimulates ASCs to release the secretome with higher antifibrotic and anti-inflammatory properties. miR-214-secretome is thus expected to be one of the prominent ways of overcoming liver fibrosis, if further studies consistently validate its safety and efficiency.

Everolimus Plus Ku0063794 Regimen Promotes Anticancer Effects against Hepatocellular Carcinoma Cells through the Paradoxical Inhibition of Autophagy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Everolimus only inhibits mammalian target of rapamycin complex 1 (mTORC1), whereas Ku0063794 inhibits both mTORC1 and mTORC2. Although they have similar anticancer effects, their combination has a synergistic effect against hepatocellular carcinoma (HCC) cells. We aimed to determine the mechanism underlying the synergistic effects of everolimus and Ku0063794 associated with autophagy in HCC cells. MATERIALS AND METHODS: We compared the effects of everolimus and Ku0063794, individually or in combination, on both the in vitro and in vivo models of HCCs. RESULTS: HepG2 cells treated with both agents had significantly lower rates of cell proliferation and higher apoptosis than the individual monotherapies (p < 0.05). Autophagic studies consistently indicated that, unlike the monotherapies, the combination therapy significantly reduced autophagy (p < 0.05). Autophagic blockage directly promoted the pro-apoptotic effects of combination therapy, suggesting autophagy as the survival mechanism of HCC cells. Unlike the monotherapies, combination therapy showed the potential to inhibit sirtuin 1 (SIRT1), the positive regulator of autophagy. SIRT1 overexpression abrogated the autophagy-inhibiting and pro-apoptotic effects of combination therapy. In a nude mouse xenograft model, the shrinkage of tumors was more prominent in mice treated with combination therapy than in mice treated with the respective monotherapies (p < 0.05). The immunohistochemical and immunofluorescence stains of the tumor obtained from the xenograft model showed that combination therapy had the potential of reducing autophagy and promoting apoptosis. CONCLUSION: The combination of everolimus and Ku0063794 potentiates anticancer effects on HCCs through a decrease in autophagy, which is prompted by SIRT1 downregulation.

17-DMAG has the Potentiated Anticancer Effects Against Hepatocellular Carcinoma Cells by Transfection of the Gene Encoding Hepatitis B Viral X Protein

BACKGROUND/AIMS: Hepatitis B viral protein X (HBx) is implicated in the pathogenesis of hepatocellular carcinoma (HCC) as well as the elevation of heat shock proteins (HSPs) after hepatitis B virus (HBV) infection. We thus investigated the anticancer effects of an HSP90 inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in HBx-transfected hepatocellular carcinoma cells. METHODS: pcDNA-HBx was made by inserting the HBx gene derived from the HBV-infected patient into pcDNA3.1 using the restriction enzymes (XbaI/HindIII). HBx-expressing HepG2 cells were then generated by transfecting HepG2 cells with pcDNA containing HBx gene. To compare the anticancer effects of 17-DMAG between pcDNA-HBx transfected HepG2 cells and the control cells (pcDNA-transfected HepG2 cells), we performed various molecular studies, including Ez-cytox proliferation assay, Western blot analysis, and flow cytometry. RESULTS: 17-DMAG inhibited the proliferation of pcDNA-HBx transfected HepG2 cells better than control cells (P<0.05). After treating with a various concentration of 17-DMAG (50–1,000 nM), pcDNA-HBx transfected HepG2 cells exhibited higher expression of pro-apoptotic proteins (c-caspase-3, c-caspase-8, and c-caspase-9) than did control cells (P<0.05). pcDNA-HBx transfected HepG2 cells showed higher activities of caspase-3, caspase-8, and caspase-9 than did control cells (P<0.05). Finally, we found that the expression of pro-apoptotic proteins (PARP and c-caspase-3) was considerably decreased by the use of a caspase inhibitor suggesting that 17-DMAG induces the cell death of HepG2 cells caspase-dependently. CONCLUSIONS: Our study strongly suggests that 17-DMAG has antiviral effects against HBV as well as anticancer effects against HepG2 cells. Thus, the application of 17-DMAG appears to be particularly advantageous to the HCC patients related with HBV infection.

The feasibility of single-port laparoscopic appendectomy using a solo approach: a comparative study

PURPOSE: To investigate the feasibility and safety of solo surgery with single-port laparoscopic appendectomy, which is termed herein solo-SPLA (solo-single-port laparoscopic appendectomy). METHODS: This study prospectively collected and retrospectively analyzed data from patients who had undergone either non-solo-SPLA (n = 150) or solo-SPLA (n = 150). Several devices were utilized for complete, skin-to-skin solo-SPSA, including a Lone Star Retractor System and an adjustable mechanical camera holder. RESULTS: Operating times were not significantly different between solo- and non-solo-SPLA (45.0 +/- 21.0 minutes vs. 46.7 +/- 26.1 minutes, P = 0.646). Most postoperative variables were also comparable between groups, including the necessity for intravenous analgesics (0.7 +/- 1.2 ampules [solo-SPLA] vs. 0.9 +/- 1.5 ampules [non-solo-SPLA], P = 0.092), time interval to gas passing (1.3 +/- 1.0 days vs. 1.4 +/- 1.0 days, P = 0.182), and the incidence of postoperative complications (4.0% vs. 8.7%, P = 0.153). Moreover, solo-SPLA effectively lowered the operating cost by reducing surgical personnel expenses. CONCLUSION: Solo-SPLA economized staff numbers and thus lowered hospital costs without lengthening of operating time. Therefore, solo-SPLA could be considered a safe and feasible alternative to non-solo-SPLA.

Liver Regenerating Potential of the Secretome Obtained from Adipose-derived Stem Cells Cultured under the Hypoxic Environment / 대한이식학회지

BACKGROUND: The stem cell-derived secretome has received considerable attention as an alternative to stem cells for therapeutic applications. However, establishing optimal culture conditions is key to obtaining appropriate secretome contents. Here, the optimal culturing environment for achieving a high-efficiency secretome was determined via hypoxic preconditioning of human adipose-derived stem cells (ASC). METHODS: Normoxic conditioned media (NCM) and hypoxic conditioned media (HCM) were obtained after culturing human ASCs under normoxia (20% O2) or hypoxia (1% O2), respectively. Subsequently, both normal and thioacetamide-induced hepatotoxic hepatocytes were treated with NCM or HCM. In addition, partially hepatectomized mice were infused with control saline, NCM, and HCM. The effects on liver regeneration and serum transaminases levels were then compared. RESULTS: Hypoxic preconditioning significantly increased mRNA expression of proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and growth factors (hepatocyte growth factor and vascular endothelial growth factor). In both normal and thioacetamide-induced hepatotoxic hepatocyte (alpha mouse liver 12 [AML12]) cell lines, HCM treatment resulted in the highest cell viability (122% and 95%, respectively), followed by NCM (111% and 78%, respectively). In addition, intravenous administration of HCM to partially hepatectomized mice resulted in substantially enhanced liver regeneration compared with the NCM group (P<0.05). CONCLUSIONS: Taken together, the secretome obtained from ASC with hypoxic preconditioning showed potential to alleviate liver damage both in vitro and in vivo. Hypoxic culture of ASC is expected to play an important role in regenerative medicine by inducing secretome production that is beneficial for improving liver regeneration.

Does Korea's current diagnosis-related group-based reimbursement system appropriately classify appendectomy patients?

PURPOSE: As several years have passed since the implementation of the Korean diagnosis-related group (DRG) payment system for appendicitis, its early outcomes should be assessed to determine if further improvements are warranted. METHODS: We retrospectively analyzed clinical data from Korean patients who underwent appendectomy, dividing the sample into 2 groups of those who received services before and after implementation of the DRG system. Based on the DRG code classification, patient data were collected including the amount of DRG reimbursement and the total in-patient costs. We subsequently performed univariate and multivariate analyses to identify independent factors contributing to higher total in-patient cost. RESULTS: Although implementation of the DRG system for appendicitis significantly reduced postoperative length of stay (2.8 ± 1.0 days vs. 3.4 ± 1.9 days, P 70 years) have greater comorbidities, which contribute to higher inpatient costs. Thus, our study suggests that patient age be considered as a DRG classification variable.

Effects of Human Adipose-Tissue Derived Stem Cell Infusion on the Immunological Consequences in Skin Allograft Mice / 대한이식학회지

BACKGROUND: Many in vitro experiments have demonstrated the immunosuppressive properties of mesenchymal stem cells (MSCs). However, such properties have not yet been fully established in an in vivo setting. The purpose of this study was to determine immunosuppressive and anti-inflammatory properties of MSCs in a preclinical animal model in order to pave the way for replacement of conventional immunosuppressive therapy. METHODS: Male C57BL/6 mice and male BALB/c mice were chosen as skin graft donors and recipients, respectively. After performance of full-thickness skin transplantation on the back of mice, adipose tissue derived stem cells (1.0x10(6)/0.1 mL) stained with 4, 6-diamidino-2-phenylindole were transplanted into adipose tissue derived stem cell (ASC)-infused mice and phosphate buffered saline (PBS; 0.1 mL) was infused into PBS-infused mice. Immunological properties and graft survival were accessed and compared. RESULTS: The serum levels of proinflammatory interleukin (IL)-6 showed a decrease in ASC-infused mice compared to PBS-infused mice (P<0.005). In addition, interferon-lambda, IL-10, and tumor necrosis factor-alpha mRNA levels in the skin graft showed a decrease in ASC-infused mice, although without statistical significance. In ASC-infused mice, donor specific hyporesponsiveness was identified in a mixed lymphocyte reaction assay at 30 days after transplantation. In addition, ASC-infusion resulted in markedly prolonged skin allograft survival compared with PBS-infusion (P<0.001). CONCLUSIONS: Administration of ASC not only induced anti-inflammation and immunosuppression, but also resulted in prolonged graft survival, suggestive of their potent immunosuppressive properties. Therefore, conduct of further and more exquisite studies will be required in order to determine the role of MSC in the solid organ transplantation field in order to avoid adverse effects and toxicities caused by chemical immunosuppressive regimens.

Therapeutic potential of adipose tissue-derived stem cells for liver failure according to the transplantation routes / 대한외과학회지

PURPOSE: Even though adipose tissue-derived stem cells (ADSCs) have been spotlighted as a possible alternative for liver transplantation in an experimental setting, the mechanism by which ADSCs improve liver dysfunction remains poorly characterized. The objective of this study was to evaluate the therapeutic ability of undifferentiated ADSCs, and find a few clues on how ADSCs alleviate liver damage by comparing the transplantation routes. METHODS: In vitro generated human ADSCs were checked for surface markers and stage-specific genes for characterization. Afterwards, they were transplanted into C57BL/6 mice with CCl4-induced liver injury. The transplantations were made via tail vein, portal vein, and direct liver parenchymal injection. At 1 and 3 post-transplantation days, serum biochemical parameters and/or liver specimens were evaluated. RESULTS: We have shown here that ADSCs have the characteristics of mesenchymal stem cells, and belong to endodermal and/or early hepatic differentiation stage. After transplantation into the mice with acute liver failure, markers of liver injury, such as alanineaminotransferase, aspartateaminotransferase, as well as ammonia, decreased. Of these transplantation routes, transplantation via tail vein rendered the most prominent reduction in the biochemical parameters. CONCLUSION: Undifferentiated ADSCs have the ability to improve hepatic function in mice with acute liver injury. Moreover, our transplantation route study supports the theory that ADSCs in systemic circulation can exert endocrine or paracrine effects to ameliorate the injured liver.

Early Experience of Single-Port Laparoscopic Anterior Resection for Colon Cancer / 대한내시경복강경외과학회지

PURPOSE: Single-port laparoscopic surgery (SPLS) has recently emerged as a method to improve the morbidity and cosmetic benefit of conventional laparoscopic surgery. We describe our experience of SPLS for an anterior resection (AR). The results of a prospective series of single-port laparoscopic anterior resection procedures are presented. METHODS: Anterior resections were performed on 16 cases using a single-port laparoscopic technique between March 2009 and March 2010. The surgical and oncologic outcomes were recorded on a prospective database. RESULTS: Sixteen (8 women) unselected patients (eight males, eight females), aged 43~82 years (median 66.5 years), underwent a SPLS anterior resection for sigmoid colon cancers (median 16 cm above AV, range 13~27). All patients were alive at 30 days. The surgery time ranged from 150~415 min (median 242 min) and the median wound incision length was 2.4 cm (range 1.5~4.0 cm). The median hospital stay was 7.5 days. Pathological reports from the resected specimens revealed adenocarcinoma in 15 patients and mucinous carcinoma in one. There was one case of an anastomotic leak that required reanastomosis. The median number of lymph nodes harvested was 27.5 (range 10~56). CONCLUSION: SPLS is a possible approach to an anterior resection with the potential for minimal access. A SPLS anterior resection is feasible and safe when performed by an experienced laparoscopic surgeon and team. On the other hand, the technique and oncologic safety warrants further prospective randomized studies.

Double Intrahepatic and Extrahepatic Cholangiocarcinomas Arising from Biliary Papillomatosis: A Case Report

Biliary papillomatosis is a rare disease entity characterized by multiple papillary adenomas along the bile duct mucosa. It is widely accepted that the adenoma-carcinoma sequence represents the process by which most, if not all, cholangiocarcinomas of an intraductal-growing type arise. Interestingly, friable papillary projections easily detached from the primary site can be implanted into the other sites in the bile duct in suitable animal models, resulting in multiple tumors. A 76-year-old male was referred to our hospital due to intermittent abdominal discomfort. Imaging workups revealed two lesions: wall thickening in the proximal portion of the left interhepatic duct and abrupt narrowing of the distal common bile duct. A hepatopancreaticoduodenectomy was carried out and pathological analysis demonstrated a well-differentiated adenocarcinoma of the left hepatic duct and carcinoma in situ of the distal common bile duct on a background of biliary papillomatosis. Six days after the operation, the patient received a re-exploration due to ruptured mesenteric vessels. Unfortunately, 3 months after the initial operation, the patient died of aspiration pneumonia. Biliary papillomatosis can present with a broad spectrum of disease characteristics ranging from adenoma to, usually, low-grade adenocarcinoma. If there is a complete excision, and a favorable postoperative course is secured, excellent survival can be expected after surgery.

Surgical Removal of Intrahepatic Bile Duct Stones Using a Rigid Nephroscope: A First Case Report

Hepatolithiasis is characterized by its frequent recurrence, and its requirement for multiple interventions which can be performed radiologically, endoscopically or surgically. Although hepatic resection - concomitant removal of hepatic stones and its provocative pathology as well - has remained the definitive treatment of hepatolithiasis, the burden of the surgery limits its widespread application. In a certain proportion of patients, those for whom hepatic resection and endoscopic/percutaneous approaches are not indicated, surgical removal of intrahepatic stones can be attempted. In those circumstances, hepatic stones located outside the direct visual field can make the stone-extracting procedure cumbersome. We experienced an operation of a 66-year-old patient who had already received left lateral sectionectomy, cholecystectomy and choledochojejunostomy. His condition was due to impacted, recurrent stones packed between the hepatic hilum and the second confluence of the hepatic duct. Instead of revising the prior choledochojejunostomy site, after entering the jejunum 4 cm below the choledochojejunostomy site, we inserted a rigid nephroscope into the hepatic duct. Under the magnified view presented by a telescope inside the nephroscope, stone extracting was easily done using forceps inserted into the nephroscope. We think a nephroscope is useful in extracting intrahepatic stones, especially for large impacted stones located below the second confluence of the hepatic duct.

Recipient's Killer Cell Immunoglobulin-like Receptor Genotype and Human Leukocyte Antigen C Ligand Influence the Clinical Outcome following Living Donor Liver Transplantation

PURPOSE: The design of this study was to determine the most influential factor(s) on post-transplant immunological consequences, particularly with regard to the role of killer cell immunoglobulin-like receptors (KIRs) and their ligands (type I human leukocyte antigen (HLA)) in unstable liver function. METHODS: Retrospectively collected data from 319 recipients undergoing adult living donor liver transplantation (LDLT) using a right lobe graft between January 2002 and August 2008 were analyzed. Patients were categorized according to the serum alanine transaminase (ALT) pattern; stable ALT pattern was defined as ALT pattern during 3 months post-transplantation, except for initial 2 weeks post-transplantation, in which 2 times or less additional elevation(s) of serum alanine transaminase (ALT) (> or =80 IU/L) were observed. When a serum ALT pattern showed fluctuating and/or unpredictable nature, it was defined as an unstable pattern. In addition, genetic information of KIRs and HLA-C allotypes received from 68 recipients and 59 donors was analyzed by way of polymerase chain reaction using sequence-specific primers (PCR-SSP) to determine the factor(s) influencing a serum ALT pattern. RESULTS: Among 319 LDLT recipients included in this study, the actual incidences of AR and unstable ALT pattern were 13.4% (43/319) and 42.3% (135/319), respectively. Unstable ALT pattern correlated with poorer survival following LDLT than stable pattern (P<0.000). Genetically, unstable ALT pattern was related to recipients carrying KIR2DL2(+)/KIR2DS2(+) combined with the heterogeneous HLA-C allotype (HLA-C1/C2), (relative risks 45.0, 95% confidence interval 2.160~937.321; P=0.013). CONCLUSION: This study indicates that, when performing LDLT, pretransplant determination of recipient's KIRs and HLA-C allotypes may be beneficial in coping with post-transplant immunological circumstances.

Completely Isolated Enteric Duplication Cyst Presenting as an Inguinal Hernia

Enteric duplication cysts are uncommon congenital anomalies whose embryogenesis remains unknown. We report here on an isolated enteric duplication cyst, that presents as an inguinal hernia. A 21-year-old woman was admitted with a month-long history of a palpable mass in the left groin. Radiologically, a computed tomography scan revealed a 3.5 x 2.5 cm sized cystic mass in subcutaneous layers of the left suprapubic area. Microscopically, the cystic wall resembled gut wall. The wall was composed of two distinct muscle layers with the presence of Auerbach's plexus. On examining the entire sections of the cyst wall very carefully, no epithelial lining was found on the inner surface. The submucosa was slightly fibrotic. The diagnosis was a completely isolated enteric duplication cyst.

The Relationship between the p27 Expression of Papillary Thyroid Cancer Cells Obtained by FNA and Cervical Lymph Node Metastasis / 대한내분비외과학회지

PURPOSE: The p27 gene as a tumor suppressor gene is associated with colorectal cancer, gastric cancer and breast cancer. Some studies have shown a relationship between the underexpression of p27 and lymph node metastasis in papillary thyroid carcinoma. The aim of this study is to evaluate the relationship between a p27 expression of the papillary thyroid cancer cells obtained by fine needle aspiration (FNA) and cervical lymph node metastasis. METHODS: This study included 60 patients with papillary thyroid cancer and who underwent total thyroidectomy or lobectomy. Central lymph node dissection was routinely done. Out of these patients, 30 patients underwent a FNA procedure during the operation. Immunohistochemical staining for p27 antibody was performed on the papillary thyroid cancer tissues and cells. RESULTS: Cervical lymph node metastasis is correlated with the tumor size and lymphovascular invasion (P<0.001). The underexpression of p27 for the papillary thyroid cancer tissues and cells was associated with lymph node metastasis (P=0.009). CONCLUSION: An evaluation of the p27 expression for the papillary thyroid cancer cells obtained by FNA may be useful as a predictor for lymph node metastasis before surgery.

Comparison of Two-port Laparoscopic Cholecystectomy with Four-port Laparoscopic Cholecystectomy

PURPOSE: In spite of its safety and fesibility, it is not completely certain whether two-port laparoscopic cholecystectomy can be applied for the same indications as four-port cholecystectomy. METHODS: We retrospectively analyzed the prospectively collected data of the patients who had undergone either two-port or four-port laparoscopic cholecystectomy at the Department of Surgery, Daejeon St. Mary's Hospital between March 2007 and August 2009. A total of 341 patients were included. For our two-port cholecystectomy, combining a transumbilical wound retractor with a surgical glove on which there was a 11 mm trocar and two pipes were attached comprised an umbilical common channel, and another port was inserted through the epigastrium. The overall procedure was similar to four-port laparoscopic cholecystectomy. RESULTS: The patients were classified into the four-port group (n=261) and the two-port group (n=80) according to the operative method. All the two-port cholecystectomies were followed by four-port procedures. The operative indications for these two procedures were identical. No significant difference was observed for the mean operation time, the conversion rate, the postoperative hospital stay and the complications between each group. Multivariate analysis revealed that the factors making two-port surgery longer than the 75 percentile of the overall operation time were the development of intraoperative complications (RR 14.3; p=0.005; C.I. 2.255-90.853), a operation for the patients who visited the emergency room (RR 10.4; p=0.012; C.I. 1.684-63.798), open conversion or making additional port(s) (RR 9.9; p=0.032; C.I. 1.219-80.958) and a body-mass index greater than 25 (RR 5.5; p=0.025; C.I. 1.244-24.731). CONCLUSION: This study documents that our two-port laparoscopic cholecystectomy seems to have the potential to replace the conventional four-port laparoscopic cholecystectomy.