Effects of Taraxaci Herba (Dandelion) on Testosterone Propionate-Induced Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly known as dandelion, has traditionally been utilized in East Asia to treat symptoms related to LUTSs. Based on this traditional use, our study aimed to explore the inhibitory effects of TH on BPH progression using a testosterone propionate-induced rat model. To induce BPH, male Sprague Dawley rats were castrated and injected subcutaneously with testosterone propionate (3 mg/kg/day) for 28 days. Concurrently, TH extract was administered orally at doses of 100 and 300 mg/kg/day throughout the four-week period of testosterone propionate injections. The TH extract significantly reduced both the absolute and relative weights of the prostate, along with histopathological changes in the gland. Moreover, it lowered serum levels of testosterone and dihydrotestosterone and reduced the expression of the androgen receptor in the prostate. Additionally, the TH extract modulated the protein expressions of Bax and Bcl-2, which are key regulators of apoptosis in prostate cells. Collectively, our findings suggest that TH inhibits BPH development partially by modulating androgen signaling and inducing apoptosis within the prostate.

Corneal lymphangiogenesis in dry eye disease is regulated by substance P/neurokinin-1 receptor system through controlling expression of vascular endothelial growth factor receptor 3.

PURPOSE: To evaluate the role of substance P (SP)/neurokinin-1 receptor (NK1R) system in the regulation of pathologic corneal lymphangiogenesis in dry eye disease (DED). METHODS: Immunocytochemistry, angiogenesis assay, and Western blot analysis of human dermal lymphatic endothelial cells (HDLECs) were conducted to assess the involvement of SP/NK1R system in lymphangiogenesis. DED was induced in wild-type C57BL/6 J mice using controlled-environment chamber without scopolamine. Immunohistochemistry, corneal fluorescein staining, and phenol red thread test were used to evaluate the effect of SP signaling blockade in the corneal lymphangiogenesis. The expression of lymphangiogenic factors in the corneal and conjunctival tissues of DED mouse model was quantified by real-time polymerase chain reaction. RESULTS: NK1R expression and pro-lymphangiogenic property of SP/NK1R system in HDLECs were confirmed by Western blot analysis and angiogenesis assay. Blockade of SP signaling with L733,060, an antagonist of NK1R, or NK1R-targeted siRNA significantly inhibited lymphangiogenesis and expression of vascular endothelial growth factor (VEGF) receptor 3 stimulated by SP in HDLECs. NK1R antagonist also suppressed pathological corneal lymphangiogenesis and ameliorated the clinical signs of dry eye in vivo. Furthermore, NK1R antagonist effectively suppressed the lymphangiogenic factors, including VEGF-C, VEGF-D, and VEGF receptor 3 in the corneal and conjunctival tissues of DED. CONCLUSIONS: SP/NK1R system promotes lymphangiogenesis in vitro and NK1R antagonism suppresses pathologic corneal lymphangiogenesis in DED in vivo.

Predictability of formulae for intraocular lens power calculation according to the age of implantation in paediatric cataract.

AIMS: To analyse the predictability of diverse intraocular lens (IOL) power calculation formulae in paediatric patients with congenital cataract. METHODS: The medical records of patients who underwent cataract surgery and posterior chamber IOL implantation (in-the-bag) for congenital cataract before 17 years of age were reviewed retrospectively. Target refractions calculated by Sanders-Retzlaff-Kraff (SRK)/II, SRK/T and Hoffer-Q formulae were compared with the actual refraction. Patients were subgroup according to the age at IOL implantation (age group 0-24 months, 25-60 months, 61-120 months, 121-203 months), and we compared mean prediction error (PE) and mean absolute error (AE) for each formula. Corrected AE was obtained by linear regression analysis. RESULTS: Totally 481 eyes were included in the final analysis. Both SRK/II and SRK/T yielded the lowest mean AE in the age group 0-24 months and SRK/II yielded the lowest mean AE in the age group 25-60 months. For every formula, the mean PE was positive during the first five years of age, which converged to zero according to age as IOL implantation increases. The tendency for immediate postoperative overcorrection in younger patients (<6 years) could be improved by corrected formulae based on the linear regression equation. CONCLUSIONS: Patients with congenital cataract who underwent IOL implantation within 5 years of age showed higher AE than the older ones did. Among the three formulae evaluated, SRK/II consistently provided the best predictive result in these patients. For patients aged >10 years, all three formulae showed favourable predictive abilities.

Prognostic influence of 3-dimensional tumor volume on breast cancer compared to conventional 1-dimensional tumor size.

PURPOSE: The prognostic influence of 3-dimensional tumor volume (Tv) on breast cancer compared to conventional 1-dimensional tumor size (T) was investigated. METHODS: Analysis was performed on a cohort of 8,996 primary breast cancer patients who were initially diagnosed with TNM stage I-III. Tumor size was defined as the maximum tumor dimension, and Tv was calculated by the equation of (4π × r1 × r2 × r3)/3; r1, r2, and r3 were defined as half of the largest, intermediate, and shortest dimension of the tumor, respectively. Tv was classified into Tv1, Tv2, and Tv3 according to the cut off values of 2.056 cm3 and 20.733 cm3. RESULTS: The survival curves according to both the T and Tv categories were clearly differentiated (all P < 0.001), as were those for staging by T and Tv (all P < 0.001). In T1 and T2 tumors, the Tv1 group showed superior survival over the Tv2 group (T1, P < 0.001; T2, P = 0.001). Univariate and multivariate analysis both indicated that Tv was a significant prognostic factor (both P < 0.001). The receiver operating characteristic curve showed that the area under the curves were 0.712 (P < 0.001) for Tv and 0.699 (P < 0.001) for T. Positive correlations were observed between the number of positive nodes and T (coefficient = 0.325; P < 0.001), and between the number of positive nodes and Tv (coefficient = 0.321; P < 0.001). CONCLUSION: Tv classification works well for predicting the prognosis of breast cancer, and it is a better predictor than conventional T classification in several aspects. Further studies are needed to validate the practical usefulness of Tv classification in clinical settings.

Estimation of Eyelid Pressure Using a Blepharo-Tensiometer in Patients with Functional Nasolacrimal Duct Obstruction.

PURPOSE: To compare the eyelid pressure between patients with functional nasolacrimal duct obstruction (FNLDO) and normal controls using blepharo-tensiometer, and to evaluate the relationship between eyelid pressure and the outcomes of silicone intubation (SI) in patients with FNLDO. STUDY DESIGN: Prospective case-control study. METHODS: We enrolled 36 eyes of 36 patients with suspected FNLDO who underwent SI and 36 healthy eyes of age-matched controls. One eye of each patient with FNLDO was randomly selected for analysis. The eyelid pressure was estimated using a blepharo-tensiometer and compared between the control and FNLDO groups. The relationship between eyelid pressure and clinical variables was analyzed. The outcomes of SI were assessed at 6 months after surgery using subjective and objective criteria. RESULTS: The eyelid pressure was significantly lower in the FNLDO group than in the control group (P=0.008). In the control group, the eyelid pressure was correlated with age (P<0.001) and lower eyelid laxity (P=0.016). In the FNLDO group, the eyelid pressure was only correlated with age (P<0.001). The success rate of SI for FNLDO was 69.4% (25 of 36 eyes). The eyelid pressure was higher in the surgical success subgroup than in the failure subgroup, although the difference was not statistically significant (P=0.08). CONCLUSIONS: Our results suggest that the eyelid pressure measured using a blepharo-tensiometer has a diagnostic value since it is decreased in patients with FNLDO. The role of eyelid pressure as a possible predictor of the outcomes of SI for FNLDO should be investigated in further studies. This trial is registered with KCT0002828.

Surgical Strategy for T2 Gallbladder Cancer: Nationwide Multicenter Survey in Korea.

BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.

Significance of distance between tumor and thyroid capsule as an indicator for central lymph node metastasis in clinically node negative papillary thyroid carcinoma patients.

The aim of this study was to evaluate preoperatively identifiable clinical and ultrasonographic characteristics associated with central lymph node metastasis (CLNM) in clinically node negative papillary thyroid carcinoma (PTC) patients. Records of the patients who underwent thyroidectomy with prophylactic central lymph node dissection due to clinically node negative PTC (size, 1.0-3.0 cm) were reviewed. Of a total of 174 patients, 71 (40.8%) had CLNMs. CLNM was more associated with capsule invasion than capsule non-invasion on ultrasonography (68.4% vs. 37.4%, p = 0.009). In the 155 patients without capsule invasion, a distance from the capsule < 1.9 mm was associated with CLNM in univariable (p = 0.002) and multivariable analysis (p < 0.001). Any PTC patient with a distance from the capsule ≥ 1.9 mm did not have CLNM whereas 40.8% (58/142) of PTC patients with a distance from the capsule < 1.9 mm had CLNM. CLNM was not associated with age, gender, or tumor size on ultrasonography. Distance from capsule ≥ 1.9 mm on preoperative ultrasonography was a significant indicator for not having CLNM in clinically node negative PTC patients. Measuring distance from the capsule on preoperative ultrasonography images could help select patients with PTC who could benefit from prophylactic central lymph node dissection.

Effect of platelet-rich plasma with self-assembled peptide on the rotator cuff tear model in rat.

Several trials have been carried out to improve the healing of rotator cuff tear, but their effects remain controversial. In this study, we examined the therapeutic effect of platelet-rich plasma (PRP) in combination with self-assembled peptide (SAP) on the healing of rotator cuff tear in the rat. Twenty-seven Sprague-Dawley rats, aged 15 weeks, were used for the rotator cuff tear model. The supraspinatus muscle at the insertion site was dissected and truncated, leaving the cut edge free. A week after the surgery, the rats were randomly divided into SAP, PRP, SAP-PRP and control groups and 0.2 ml SAP, PRP, SAP-PRP and saline were injected, respectively. Bonar scores and synovial inflammation grade were checked 5 weeks after the injection. Immunofluorescence staining for heat shock protein (HSP)-70 and caspase-3 was conducted. Furthermore, maximum stride length was measured before and at 2 and 4 weeks after the injection. The Bonar scores were 6.4 ± 1.8 in the SAP group, 5.9 ± 2.0 in the PRP group, 4.7 ± 1.1 in the SAP-PRP group and 8.3 ± 2.3 in the control group. There was significant difference between the SAP-PRP and control groups in post hoc multiple comparison analysis. Among four categories of Bonar scores, collagen arrangement and vascular infiltration showed improvement after SAP-PRP injection. Immunofluorescence images showed that HSP-70 and caspase-3 were much less expressed in the SAP-PRP group than in the other groups. In conclusion, SAP-PRP can be effective in healing a rotator cuff tear by enhancing the collagen arrangement and inhibiting inflammatory changes and apoptosis. Copyright © 2015 John Wiley & Sons, Ltd.

Pre-Hepatectomy Assessment of Bile Transporter Expression by Gadoxetic Acid-Enhanced MRI in a Rat Model of Liver Cirrhosis.

BACKGROUND: Gadoxetic acid is a liver-specific intravenous T1 magnetic resonance (MR) contrast agent that is excreted via the hepatobiliary system. We hypothesize that hepatocyte expressions of bile transporters (OATP1 and MRP2) correlate with dynamic profile of Gadoxetic acid enhanced (GE)-MR imaging (MRI). METHODS: Two groups of rats, control (n = 6) and cirrhosis (n = 12), received gadoxetic acid enhanced MRI followed by 70% hepatectomy. The change in MR signal intensity from the baseline before the contrast injection (ΔSI) was analyzed every minute for 30 min. Dynamic signal intensity retention ratio (DSR) was defined as the mean ΔSI of the third 10-minmin period divided by the first 10-minmin period. Real-time PCR was utilized to quantify mRNA expressions. RESULTS: Compared to the control, cirrhosis group demonstrated lower mRNA levels of OATP1 (0.038 ± 0.020 vs. 0.232 ± 0.0979; p = 0.004), MRP2 (0.201 ± 0.084 vs. 0.7567 ± 0.254; p = 0.002), and OATP1/MRP2 mRNA ratio (0.193 ± 0.065 vs. 0.342 ± 0.206; p = 0.032). DSR was higher in the cirrhosis group (0.678 ± 0.554 vs -0.125 ± 0.839; p = 0.033). In the cirrhosis group, there was an inverse correlation between the ratios of OATP1/MRP2 mRNA and DSR (R = -0.709, p = 0.01). CONCLUSION: Bile transporters OATP1/MRP2 mRNA expression ratio in rat liver tissue decreased with DMN-induced liver injury. The expressions of bile transporters correlated with GE-MRI DSR. The GE-MRI DSR has potential utility in qualifying OATP1/MRP2 mRNA expression.

Predictors of Morbidity and Mortality After Surgery for Intestinal Perforation.

PURPOSE: An intestinal perforation is a rare condition, but has a high mortality rate, even after immediate surgical intervention. The clinical predictors of postoperative morbidity and mortality are still not well established, so this study attempted to identify risk factors for postoperative morbidity and mortality after surgery for an intestinal perforation. METHODS: We retrospectively analyzed the cases of 117 patients who underwent surgery for an intestinal perforation at a single institution in Korea from November 2008 to June 2014. Factors related with postoperative mortality at 1 month and other postoperative complications were investigated. RESULTS: The mean age of enrolled patients was 66.0 ± 15.8 years and 66% of the patients were male. Fifteen patients (13%) died within 1 month after surgical treatment. Univariate analysis indicated that patient-related factors associated with mortality were low systolic and diastolic blood pressure, low serum albumin, low serum protein, low total cholesterol, and high blood urea nitrogen; the surgery-related factor associated with mortality was feculent ascites. Multivariate analysis using a logistic regression indicated that low systolic blood pressure and feculent ascites independently increased the risk for mortality; postoperative complications were more likely in both females and those with low estimated glomerular filtration rates and elevated serum C-reactive protein levels. CONCLUSION: Various factors were associated with postoperative clinical outcomes of patients with an intestinal perforation. Morbidity and mortality following an intestinal perforation were greater in patients with unstable initial vital signs, poor nutritional status, and feculent ascites.

Long-term Outcomes and Risk Factors for Reoperation After Surgical Treatment for Gastrointestinal Crohn Disease According to Anti-tumor Necrosis Factor-α Antibody Use: 35 Years of Experience at a Single Institute in Korea.

PURPOSE: Crohn disease is characterized by high rates of recurrence and reoperations. However, few studies have investigated long-term surgical outcomes in Asian populations. We investigated risk factors for reoperation, particularly those associated with anti-tumor necrosis factor-α (anti-TNF-α) antibody use, and long-term follow-up results. METHODS: We reviewed the records of 148 patients (100 males and 48 females) who underwent surgery for gastrointestinal Crohn disease and retrospectively analyzed long-term outcomes and risk factors. RESULTS: The mean age at diagnosis was 28.8 years. Thirty-eight patients (25.7%) received monoclonal antibody treatment before reoperation. A small bowel and colon resection was most commonly performed (83 patients, 56.1%). The median follow-up was 149 months, during which 47 patients underwent reoperation. The median interval between the primary and the secondary surgeries was 65 months, with accumulated reoperation rates of 16.5%, 31.8%, and 57.2% after 5, 10, and 15 years, respectively. Obstruction was the most common indication for reoperation (37 patients, 25.0%). In a multivariable analysis, age <17 years at diagnosis (A1) (odds ratio [OR], 2.20; P = 0.023), penetrating behavior (B3) (OR, 4.39; P < 0.001), and no azathioprine use (OR, 2.87; P = 0.003) were associated with reoperation. Anti-TNF-α antibody use did not affect the reoperation rate (P = 0.767). CONCLUSION: We showed a high reoperation rate regardless of treatment with anti-TNF-α antibody, which indicates that recurrent surgery is still needed to cure patients with gastrointestinal Crohn diseases. Younger age at primary operation, penetrating behavior, and no azathioprine use were significant factors associated with reoperation for gastrointestinal Crohn disease.

Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery.

It has been challenging for microneedles to deliver drugs effectively to thin tissues with little background support such as the cornea. Herein, we designed a microneedle pen system, a single microneedle with a spring-loaded microneedle applicator to provide impact insertion. To firmly attach solid microneedles with 140 µm in height at the end of macro-scale applicators, a transfer molding process was employed. The fabricated microneedle pens were then applied to mouse corneas. The microneedle pens successfully delivered rhodamine dye deep enough to reach the stromal layer of the cornea with small entry only about 1000 µm(2). When compared with syringes or 30 G needle tips, microneedle pens could achieve more localized and minimally invasive delivery without any chances of perforation. To investigate the efficacy of microneedle pens as a way of drug delivery, sunitinib malate proven to inhibit in vitro angiogenesis, was delivered to suture-induced angiogenesis model. When compared with delivery by a 30 G needle tip dipped with sunitinib malate, only delivery by microneedle pens could effectively inhibit corneal neovascularization in vivo. Microneedle pens could effectively deliver drugs to thin tissues without impairing merits of using microneedles: localized and minimally invasive delivery.

VEGF-trap aflibercept significantly improves long-term graft survival in high-risk corneal transplantation.

BACKGROUND: Graft failure because of immune rejection remains a significant problem in organ transplantation, and lymphatic and blood vessels are important components of the afferent and efferent arms of the host alloimmune response, respectively. We compare the effect of antihemangiogenic and antilymphangiogenic therapies on alloimmunity and graft survival in a murine model of high-risk corneal transplantation. METHODS: Orthotopic corneal transplantation was performed in hemevascularized and lymph-vascularized high-risk host beds, and graft recipients received subconjunctival vascular endothelial growth factor (VEGF)-trap, anti-VEGF-C, sVEGFR-3, or no treatment, beginning at the time of surgery. Fourteen days after transplantation, graft hemeangiogenesis and lymphangiogenesis were evaluated by immunohistochemistry. The frequencies of Th1 cells in regional lymphoid tissue and graft-infiltrating immune cells were evaluated by flow cytometry. Long-term allograft survival was compared using Kaplan-Meier curves. RESULTS: VEGF-trap significantly decreased graft hemangiogenesis as compared to the control group and was most effective in reducing the frequency of graft-infiltrating immune cells. Anti-VEGF-C and sVEGFR3 significantly decreased graft lymphangiogenesis and lymphoid Th1 cell frequencies as compared to control. VEGF-trap (72%), anti-VEGF-C (25%), and sVEGFR-3 (11%) all significantly improved in the 8-week graft survival compared to control (0%), although VEGF-trap was significantly more effective than both anti-VEGF-C (P < 0.05) and sVEGFR-3 (P < 0.05). CONCLUSION: In a clinically relevant model of high-risk corneal transplantation in which blood and lymphatic vessels are present and treatment begins at the time of transplantation, VEGF-trap is significantly more effective in improving long-term graft survival as compared to anti-VEGF-C and sVEGFR-3, but all approaches improve survival when compared to untreated control.

Extraorbital lacrimal gland excision: a reproducible model of severe aqueous tear-deficient dry eye disease.

PURPOSE: The aim of this study was to establish and characterize extraorbital lacrimal gland excision (LGE) as a model of aqueous tear-deficient dry eye disease in mice. METHODS: Female C57BL/6 mice at 6 to 8 weeks of age were randomized to extraorbital LGE, sham surgery, or scopolamine groups. Mice that underwent extraorbital LGE or sham surgery were housed in the standard vivarium. Scopolamine-treated mice were housed in a controlled environment chamber that allowed for the continuous regulation of airflow (15 L/min), relative humidity (30%), and temperature (21-23°C). Clinical disease severity was assessed over the course of 14 days using the phenol red thread test and corneal fluorescein staining. Real-time polymerase chain reaction was performed to assess corneal mRNA expression of interleukin 1ß, tumor necrosis factor α, and matrix metalloproteinase 9. Flow cytometry was used to assess T helper cell frequencies in the conjunctivae and draining lymph nodes. RESULTS: Extraorbital LGE markedly reduced aqueous tear secretion as compared with the sham procedure and induced a more consistent decrease in aqueous tear secretion than was observed in mice that received scopolamine while housed in the controlled environment chamber. Extraorbital LGE significantly increased corneal fluorescein staining scores as compared with those of both the sham surgery and scopolamine-treated groups. Extraorbital LGE significantly increased the corneal expression of interleukin 1ß, tumor necrosis factor α, and matrix metalloproteinase 9. Further, extraorbital LGE increased T helper 17-cell frequencies in the conjunctivae and draining lymph nodes. CONCLUSIONS: Extraorbital LGE induces aqueous tear-deficient dry eye disease in mice as evidenced by decreased aqueous tear secretion, increased corneal epitheliopathy, and induced ocular surface inflammation and immunity.

Effect of self-assembled peptide-mesenchymal stem cell complex on the progression of osteoarthritis in a rat model.

PURPOSE: To evaluate the efficacy of mesenchymal stem cells (MSCs) encapsulated in self-assembled peptide (SAP) hydrogels in a rat knee model for the prevention of osteoarthritis (OA) progression. MATERIALS AND METHODS: Nanostructured KLD-12 SAPs were used as the injectable hydrogels. Thirty-three Sprague Dawley rats were used for the OA model. Ten rats were used for the evaluation of biotin-tagged SAP disappearance. Twenty-three rats were divided into four groups: MSC (n=6), SAP (n=6), SAP-MSC (n=6), and no treatment (n=5). MSCs, SAPs, and SAP-MSCs were injected into the knee joints 3 weeks postsurgery. Histologic examination, immunofluorescent staining, measurement of cytokine levels, and micro-computed tomography analysis were conducted 6 weeks after injections. Behavioral studies were done to establish baseline measurements before treatment, and repeated 3 and 6 weeks after treatment to measure the efficacy of SAP-MSCs. RESULTS: Concentration of biotinylated SAP at week 1 was not significantly different from those at week 3 and week 6 (P=0.565). Bone mineral density was significantly lower in SAP-MSC groups than controls (P=0.002). Significant differences in terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining between the control group and all other groups were observed. Caspase-8, tissue inhibitor of metalloproteinases 1, and matrix metalloproteinase 9 were diffusely stained in controls, whereas localized or minimal staining was observed in other groups. Modified Mankin scores were significantly lower in the SAP and SAP-MSC groups than in controls (P=0.001 and 0.013). Although not statistically significant, synovial inflammation scores were lower in the SAP (1.3±0.3) and SAP-MSC (1.3±0.2) groups than in controls (2.6±0.2). However, neither the cytokine level nor the behavioral score was significantly different between groups. CONCLUSION: Injection of SAP-MSC hydrogels showed evidence of chondroprotection, as measured by the histologic grading and decreased expression of biochemical markers of inflammation and apoptosis. It also lowered subchondral bone mineral density, which can be increased by OA. This suggests that the SAP-MSC complex may have clinical potential to inhibit OA progression.

Preoperative 18F-FDG PET-CT maximum standardized uptake value predicts recurrence of biliary tract cancer.

(18)F-Fluorodeoxyglucose positron-emission with computed tomography ((18)F-FDG PET-CT) is an imaging technique based on the increased uptake of glucose characteristically seen in malignant lesions. The preoperative maximum standardized uptake value (SUVmax) of PET-CT has been identified as a powerful significant prognostic factor for predicting recurrence in malignant tumors. Therefore, the aim of this study was to determine whether (18)F-FDG PET-CT has a prognostic significance in patients with biliary tract cancer after surgical resection. From April 2006 to February 2013, 64 patients who underwent curative resection for biliary tract cancer were reviewed retrospectively. Clinical diagnoses of patients were: intrahepatic cholangio-carcinoma (n=6), hilar cholangiocarcinoma (n=6), extrahepatic cholangiocarcinoma (n=22), gall bladder cancer (n=14) and ampullar cancer (n=16). The mean preoperative SUVmax value was 5.1±4.7. The mean follow-up duration was 27 months. Recurrence-free survival at 1, 2 and 5 years were 75.9%, 63.3% and 47.1%. In the univariate analysis, N stage, poor tumor differentiation, the presence of lymphatic invasion and high SUVmax (>5.0) were significant risk factors for recurrence. The multivariate analysis showed a high preoperative SUVmax (>5.0) to be an independent risk factor for tumor recurrence (p=0.008). In conclusion, preoperative SUVmax of the primary tumor was significantly associated with recurrence in patients with biliary tract cancer.

Surgical strategy for T1 gallbladder cancer: a nationwide multicenter survey in South Korea.

BACKGROUND: The aim of this study was to investigate the clinical features and clinical outcomes of T1 gallbladder (GB) cancer and to determine an appropriate surgical strategy for T1 GB cancer. METHODS: A nationwide multicenter study, in which 16 University Hospitals in Korea participated, was performed from 1995 to 2004. A total of 258 patients, 117 patients with T1a and 141 patients with T1b disease were enrolled. Clinicopathologic findings and long-term follow-up results were analyzed after a consensus meeting of the Korean Pancreas Surgery Club was held. RESULTS: Simple cholecystectomy was performed in 95 patients (81.2 %) with T1a tumor and in 89 patients (63.1 %) with T1b tumor (p < 0.01). Lymph node metastasis was observed in 2.9 % of T1a patients and in 9.9 % of T1b patients (p = 0.391). A significant difference in 5-year disease-specific survival (DSS) rates was observed between T1a and T1b patients (96.4 vs 84.8 %, respectively, p = 0.03). However, no significant 5-year DSS rate difference was observed between those who underwent simple cholecystectomy or extended cholecystectomy, regardless of whether lymph node dissection was performed or whether lymph node metastasis was present. There was no significant difference in recurrence-free survival between simple cholecystectomy and extended cholecystectomy. CONCLUSIONS: There was no superiority of extended cholecystectomy over simple cholecystectomy in the aspect of survival and recurrence especially in T1b gallbladder cancer. Furthermore, the effectiveness of regional lymphadenectomy for treatment purpose remains questionable. Therefore, simple cholecystectomy could be recommended as a surgical strategy of T1 gallbladder cancer.

TXNDC5 gene polymorphism contributes to increased risk of hepatocellular carcinoma in the Korean male population.

Thioredoxin domain-containing protein-5 (TXNDC5) has been found to be associated with cancer development and growth. We investigated whether TXNDC5 gene polymorphisms are associated with hepatocellular carcinoma (HCC) in a Korean male population. Seven SNPs were selected based on minor allelic frequency (≥5%). The SNPs consisted of three exonic SNPs (rs8643, rs7764128 and rs1043784) and four intronic SNPs (rs1225944, rs1225943, rs1225945 and rs1225958). We selected and assessed these SNPs in 160 patients with HCC and 178 controls. Genetic data were analyzed using SNPAnalyzer Pro, SNPStats, and Haploview programs. Two SNPs of the TXNDC5 gene were found to be associated with the risk of HCC development. The genotypic frequency of rs1225944 was associated with HCC in the recessive model [CC/CT vs. TT, p=0.43, Fisher's exact test p=0.032; odds ratio (OR)=0.54, 95% confidence interval (CI)=0.11-2.71]. The genotypic frequency of rs1225943 was associated with HCC in the co-dominant 2 (AA vs. CC, p=0.07; Fisher's exact test p=0.001, OR=0.23, 95% CI=0.05-1.10), recessive (AA/AC vs. CC, p=0.044, Fisher's exact test p=0.001, OR=0.25, 95% CI=0.05-1.17), and log-additive models (p=0.08, Fisher's exact test p=0.002, OR=0.68, 95% CI=0.44-1.05). The haplotype CA and TC of rs1229544 and rs1225943, demonstrated a significant association with HCC. Our results suggest that TXNDC5 polymorphisms could be related to the development of HCC in the Korean male population.

Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X1 receptor channel currents.

Ginseng, the root of Panax ginseng C.A. Meyer, is used as a general tonic. Recently, we isolated a novel ginsengderived lysophosphatidic acid (LPA) receptor ligand, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity in cells endogenously expressing LPA receptors, e.g., Xenopus oocytes. P2X receptors are ligandgated ion channels activated by extracellular ATP, and 7 receptor subtypes (P2X1-P2X7) have been identified. Most of the P2X1 receptors are expressed in the smooth muscles of genitourinary organs involved in reproduction. A main characteristic of the P2X1 receptor is rapid desensitization after repeated ATP treatment of cells or tissues expressing P2X1 receptors. In the present study, we examined the effect of gintonin on P2X1 receptor channel activity. P2X1 receptors were heterologously expressed in Xenopus oocytes. ATP treatment of oocytes expressing P2X1 receptors induced large inward currents (I ATP ), but repetitive ATP treatments induced a rapid desensitization of I ATP . Gintonin treatment after P2X1 receptor desensitization potentiated I ATP in a concentration-dependent manner. We further examined the signaling transduction pathways involved in gintonin-mediated potentiation of I ATP . Gintoninmediated I ATP potentiation was blocked by Ki16425, an LPA1/3 receptor antagonist, a PKC inhibitor, a PLC inhibitor, and a PI4-Kinase inhibitor but not by a calcium chelator. In addition, mutations of the phosphoinositide binding site of the P2X1 receptor greatly attenuated the gintonin-mediated I ATP potentiation. These results indicate that G protein-coupled LPA receptor activation by gintonin is coupled to the potentiation of the desensitized P2X1 receptor through a phosphoinositide-dependent pathway.