[Show abstract][Hide abstract] ABSTRACT: Patient-derived tumor xenograft is the transfer of primary human tumors directly into an immunodeficient mouse. Patient-derived tumor xenograft plays an important role in the development and evaluation of new chemotherapeutic agents. We succeeded in generating a patient-derived tumor xenograft of a biliary tumor obtained by endoscopic ultrasound-guided fine-needle aspiration from a patient who had an inoperable extrahepatic cholangiocarcinoma. This patient-derived tumor xenograft will be a promising tool for individualized cancer therapy and can be used in developing new chemotherapeutic agents for the treatment of biliary cancer in the future.
Gut and Liver 06/2015; DOI:10.5009/gnl14279 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Actinomycosis is a chronic suppurative granulomatous infectious disease caused by actinomyces species that is characterized by formation of characteristic clumps called as sulfur granules. Abdominal actinomycosis is a rare disease and is often difficult to diagnose before operation. Abdominal actinomycosis infiltrating into the abdominal wall and adhering to the colon is even rarer. Most abdominal actinomycosis develops after operation, trauma or inflammatory bowel disease, and is also considered as an opportunistic infection in immunocompromised patient with underlying malignancy, diabetes mellitus, human immunodefidiency virus infection, etc. Actinomycosis is diagnosed based on histologic demonstration of sulfur granules in surgically resected specimen or pus, and treatment consists of long-term penicillin based antibiotics therapy with or without surgical resection. Herein, we report an unusual case of abdominal wall actinomycosis which developed in a patient after acupuncture and presented as abdominal wall mass that was first mistaken for abdominal wall invasion of diverticulum perforation.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 04/2015; 65(4):236-40. DOI:10.4166/kjg.2015.65.4.236
[Show abstract][Hide abstract] ABSTRACT: Lymph node metastasis is an important factor for predicting the prognosis of colorectal cancer patients. However, approximately 60% of patients do not receive adequate lymph node evaluation(less than 12 lymph nodes). In this study, we identified a more effective tool for predicting the prognosis of patients who received inadequate lymph node evaluation.
The number of metastatic lymph nodes (ML), total number of lymph nodes examined (TL), number of negative metastatic lymph nodes (NL), lymph node ratio (LR) and the number of apical lymph nodes (APL) were examined, and the prognostic impact of these parameters wasexamined in patients with colorectal cancer who underwent surgery from January 2004 to December 2011. In total, 806 people were analyzed retrospectively.
In comparisonof different lymph node analysis methods for rectal cancer patients who did not receive adequate lymph node dissection, the LR showed a significant difference in overall survival (OS) and the APL predicted a significant difference in disease free survival (DFS). In the case of colon cancer patients who did not receive adequate lymph node dissection, LR predicted a significant difference in DFS and OS, and the APL predicted a significant difference in DFS.
If patients did not receive adequate lymph node evaluation, the LR and NL were useful parameters to complement N stage for predicting OS in colon cancer, whereas LR was complementary for rectal cancer. The APL could be used for prediction of DFS in all patients.
Cancer Research and Treatment 04/2015; DOI:10.4143/crt.2014.312 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 56-year-old female patient presented with sustained sigmoid colon perforation at the time of a tension-free vaginal tape (TVT) procedure and subsequently developed enterocutaneous fistula and subcutaneous abscess. She came to our emergency department complaining of left lower abdominal tenderness and swelling for 2 weeks previously. Her right thigh also was tender and swollen. A foreign body in sigmoid colon and subcutaneous abscess were found on computed tomography scan. We diagnosed the perforation of sigmoid colon and enterocutaneous fistula by TVT mesh. We performed laparoscopic excision of the mesh in sigmoid colon. We performed transobturator tape surgery for recurrence of stress urinary incontinence after 6 months.
[Show abstract][Hide abstract] ABSTRACT: This study investigated the association between the frequency of growth hormone receptor (GHR) exon 3 polymorphism (exon 3 deletion; d3-GHR) and metabolic factors in patients with acromegaly in Korea.
DNA was extracted from the peripheral blood of 30 unrelated patients with acromegaly. GHR genotypes were evaluated by polymerase chain reaction (PCR) and correlated with demographic data and laboratory parameters.
No patient had the d3/d3 genotype, while four (13.3%) had the d3/fl genotype, and 26 (86.7%) had the fl/fl genotype. Body mass index (BMI) in patients with the d3/fl genotype was significantly higher than in those with the fl/fl genotype (P=0.001). Age, gender, blood pressure, insulin-like growth factor-1, growth hormone, fasting plasma glucose, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol levels showed no significant differences between the two genotypes.
The d3-GHR polymorphism may be associated with high BMI but not with other demographic characteristics or laboratory parameters.
[Show abstract][Hide abstract] ABSTRACT: Background
Laparoscopic surgery for rectal cancer is technically demanding and can be hindered by unexpected intra-operative complications. Among the various intra-operative complications, double-stapled anastomotic complications are more serious and complicated to manage. The purpose of this study is to analyze the impact of intra-operative double-stapled colorectal or coloanal anastomotic complications on short-term surgical outcomes and persistent leak, and risk factors of intra-operative double-stapled anastomotic complication.
Consecutive 363 cases of laparoscopic low anterior resection from August 2004 to November 2012 were analyzed in this study. We retrospectively reviewed intra-operative double-stapled anastomotic complications and compared patient characteristics, surgical data, post-operative clinical data, and pathological data between groups with and without intra-operative double-stapled anastomotic complications. And we analyzed risk factors for double-stapled anastomotic complication.
There were 20 intra-operative double-stapled anastomotic complications among the patients (5.5 %). Operation time was longer (304.8 ± 122.0 vs. 197.1 ± 87.5 min, p = 0.001) and more diversion ileostomy were made (75 vs. 34.7 %, p
[Show abstract][Hide abstract] ABSTRACT: To compare the efficacy and safety of anagliptin and sitagliptin as an add-on to metformin in patients with type 2 diabetes, we conducted a 24-week, multi-center, double-blind, randomized study with a 28-week extension. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88) group. The primary endpoint was the change in HbA1c from baseline to Week 24. The mean changes in HbA1c were −0.85 ± 0.70% (p < 0.0001) for anagliptin and −0.83 ± 0.61 % (p < 0.0001) for sitagliptin, with a mean difference of −0.02% (95% confidence interval of difference, −0.22 to 0.18%). In both groups, fasting proinsulin/insulin ratio significantly decreased from baseline, with improved insulin secretion. Safety profiles were comparable between groups. In conclusion, non-inferiority of the efficacy of anagliptin to sitagliptin was established as an add-on therapy, regarding efficacy and safety.
[Show abstract][Hide abstract] ABSTRACT: GSK5182 (4-[(Z)-1-[4-(2-Dimethylaminoethyloxy)phenyl]-hydroxy-2-phenylpent-1-enyl]phenol) is a specific inverse agonist for estrogen-related receptor γ, a member of the orphan nuclear receptor family that has important functions in development and homeostasis. This study was performed to elucidate the metabolites of GSK5182 and to characterize the enzymes involved in its metabolism. Incubation of human liver microsomes with GSK5182 in the presence of NADPH resulted in the formation of three metabolites, M1, M2, and M3. M1 and M3 were identified as N-desmethyl-GSK5182 and GSK5182 N-oxide, respectively, on the basis of liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. M2 was suggested to be hydroxy-GSK5182 through interpretation of its MS/MS fragmentation pattern. In addition, the specific cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) isoforms responsible for GSK5182 oxidation to the three metabolites were identified using a combination of correlation analysis, chemical inhibition in human liver microsomes, and metabolism by expressed recombinant P450 and FMO isoforms. GSK5182 N-demethylation and hydroxylation is mainly mediated by CYP3A4, whereas FMO1 and FMO3 contribute to the formation of GSK5182 N-oxide from GSK5182. The present data will be useful to understand the pharmacokinetics and drug interactions of GSK5182 in vivo. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background
We evaluated the disease profile and clinical management, including the status of both glycemic control and complications, in patients with diabetes who were transferred to referral hospitals in Korea.
Patients referred to 20 referral hospitals in Gyeongsangnam/Gyeongsangbuk-do and Jeollanam/Jeollabuk-do with at least a 1-year history of diabetes between January and June 2011 were retrospectively reviewed using medical records, laboratory tests, and questionnaires.
A total of 654 patients were enrolled in the study. In total, 437 patients (67%) were transferred from clinics and 197 (30%) patients were transferred from hospitals. A total of 279 patients (43%) visited higher medical institutions without a written medical request. The main reason for the referral was glycemic control in 433 patients (66%). Seventy-three patients (11%) had received more than one session of diabetic education. Only 177 patients (27%) had been routinely self-monitoring blood glucose, and 146 patients (22%) were monitoring hemoglobin A1c. In addition, proper evaluations for diabetic complications were performed for 74 patients (11%). The most common complication was neuropathy (32%) followed by nephropathy (31%). In total, 538 patients (82%) had been taking oral hypoglycemic agents. A relatively large number of patients (44%) had been taking antihypertensive medications.
We investigated the clinical characteristics of diabetic patients and identified specific problems in diabetic management prior to the transfer. We also found several problems in the medical system, which were divided into three medical institutions having different roles in Korea. Our findings suggested that the relationships among medical institutions have to be improved, particularly for diabetes.
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
The metabolism of glutamine and glucose is recognized as a promising therapeutic target for the treatment of cancer; however, targeted molecules that mediate glutamine and glucose metabolism in cancer cells have not been addressed. Here, we show that restricting the supply of glutamine in hepatoma cells, including HepG2 and Hep3B cells, markedly increased the expression of retinoic acid-related orphan receptor alpha (RORα). Up-regulation of RORα in glutamine-deficient hepatoma cells resulted from an increase in the level of cellular reactive oxygen species and in the nicotinamide adenine dinucleotide phosphate/nicotinamide adenine dinucleotide phosphate reduced (NADP+ /NADPH) ratio, which was consistent with a reduction in the glutathione/glutathione disulfide (GSH/GSSG) ratio. Adenovirus (Ad)-mediated overexpression of RORα (Ad-RORα) or treatment with the RORα activator, SR1078, reduced aerobic glycolysis and down-regulated biosynthetic pathways in hepatoma cells. Ad-RORα and SR1078 reduced the expression of pyruvate dehydrogenase kinase 2 (PDK2) and inhibited the phosphorylation of pyruvate dehydrogenase and subsequently shifted pyruvate to complete oxidation. The RORα-mediated decrease in PDK2 levels was caused by up-regulation of p21, rather than p53. Furthermore, RORα inhibited hepatoma growth both in vitro and in a xenograft model in vivo. We also found that suppression of PDK2 inhibited hepatoma growth in a xenograft model. These findings mimic the altered glucose utilization and hepatoma growth caused by glutamine deprivation. Finally, tumor tissue from 187 hepatocellular carcinoma patients expressed lower levels of RORα than adjacent nontumor tissue, supporting a potential beneficial effect of RORα activation in the treatment of liver cancer.
RORα mediates reprogramming of glucose metabolism in hepatoma cells in response to glutamine deficiency. The relationships established here between glutamine metabolism, RORα expression and signaling, and aerobic glycolysis have implications for therapeutic targeting of liver cancer metabolism.
[Show abstract][Hide abstract] ABSTRACT: Abstract Text:
This study was performed to determine the effects of road transportation on metabolic responses in dairy heifers. Twenty-two Holstein heifers (average 17.6 months of age, 440 kg of average body weight) were divided into non-transported (NT; n = 8) and transported (T; n = 14) groups. Feed and water in the NT heifers were restricted the same amount as the T heifers. The heifers were acclimated in stanchion barn. All heifers were restrained with a halter in a stanchion, and blood was collected using vaccutainer by jugular venipuncture. The NT heifers In the T group, blood was collected before transportation (BT), after 100km (T1) and 200km transportation (T2), and at 24h after transportation (AT). In the NT group, blood was collected at same time as the T group. The T heifers showed higher (P < 0.001) blood cortisol concentrations after T1 and T2 than the NT heifers. The T heifers showed higher (P < 0.01) serum non-esterified fatty acid (NEFA) concentrations after T1 and T2 than the NT heifers. In contrast, the T heifers showed lower serum triglyceride (TG) concentrations after T1 (P = 0.01) and T2 (P < 0.001) than the NT heifers. Serum concentrations of cortisol, NEFA, and TG at 24h AT were returned (P > 0.05) to those of the BT in the T heifers. Other serum lipid concentrations, including phospholipid (P = 0.02), high density lipoprotein (P = 0.03), low density lipoprotein (P = 0.01), and cholesterol (P = 0.04) were lower in the T heifers after T2 than the NT heifers. Serum glucose concentrations were not changed by T1 and T2. The ratio of granulocytes to lymphocytes (P < 0.001) and the percentage of monocytes (P < 0.05) were shown higher after T2 in the T heifers when compared to those of the NT heifers, suggesting increased number of innate immune cells upon transportation stress. In conclusion, short transportation increases cortisol secretion, which was coincident with induction of metabolic responses and up-regulation of peripheral innate immune cells in dairy heifers.
Keywords: transportation, stress, metabolic responses, dairy heifers
[Show abstract][Hide abstract] ABSTRACT: Purpose:
While the incidence of right colonic diverticulitis (RCD) is rare in Western countries, the right colon is the most common site of diverticulitis in Asian countries. However, its recurrent pattern and management were rarely studied. This study was designed to elucidate the pattern of recurrence in RCD.
Of the 154 patients admitted as right colonic diverticulitis between February 2004 and March 2012, 104 patients were enrolled, prospectively. The recurrence rate, size, multiplicity, location, diagnostic criteria score, and predisposing factors were evaluated based on Hinchey's classification of diverticulitis.
There were 104 patients with right colonic diverticulitis in this study, and 20 patients (19.2 %) recurred after medical treatment. When the diverticula were not located in the right colon, the recurrence rate was significantly higher than the diverticula located only in the right colon (p = 0.004). The recurrence rate of diverticulitis for a single diverticulum was significantly lower than that for multiple diverticula (p = 0.02). Of the 20 patients with recurrence, 1 (5 %) patient underwent laparoscopic diverticulectomy due to a misdiagnosis of diverticulitis as appendicitis. The remaining 19 patients (95 %) received nonoperative management and recovered without any sequelae.
The recurrence rate was 19.2 %, and the predisposing factors were the location of diverticula and the multiplicity of primary diverticula. The re-recurrence rate of recurred patients was 26.3 %. The recurred lesions were controlled simply by nonoperative management. Elective surgery was also a treatment option.
International Journal of Colorectal Disease 07/2014; 29(11). DOI:10.1007/s00384-014-1938-3 · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We analyzed the characteristics of gastrointestinal neuroendocrine tumors and examined the outcomes and safety of modalities in rectal neuroendocrine tumors.
Between 2007 and 2011, a total of 91 patients with gastrointestinal neuroendocrine tumors were retrospectively reviewed in terms of the characteristics of tumors.
Sixty-six patients had rectal neuroendocrine tumors and underwent endoscopic mucosal resection (EMR, n = 29), endoscopic submucosal dissection (ESD, n = 23), or transanal endoscopic microsurgery (TEM, n = 14). The complete resection rate was higher in the ESD group (82.7%) and in the TEM group (100%) compared to the EMR group (65.5%) (P < 0.046). The complication rate was higher in the ESD group (47.8%) than in the EMR group (18.5%) (P = 0.003). No local tumor recurrence was observed in all patients, regardless of the procedure, during the median follow-up period of 21.5 ± 13.5 months.
ESD achieved a higher complete resection rate than EMR and comparable to TEM. Tumor recurrence was not observed in the endoscopic resection and TEM groups, regardless of the completeness of resection. Small neuroendocrine tumors of the gastrointestinal tract can be managed reliably with both endoscopic resection and TEM.
[Show abstract][Hide abstract] ABSTRACT: A single gene mutation alone cannot explain the poor prognosis of colorectal cancer. This study aimed to establish a correlation between the expression of six proteins and the prognosis of colorectal cancer patients.
Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer at our institution from January 2006 to December 2007. The expression of six proteins were determined using immunohistochemical staining of specimens.
Cathepsin D, p53, COX-2, epidermal growth factor receptor, c-erbB-2, and Ki-67 expression were detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and colorectal cancer-specific survival (p=0.003), but the other expression levels were not. In a multivariate analysis, cathepsin D expression was found to be an independent prognostic factor for poorer colorectal cancer-specific survival (hazard ratio, 8.55; 95% confidence interval, 1.07 to 68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and colorectal cancer-specific survival rate (p=0.002).
Patients with cathepsin D positivity had a poorer outcome than patients who were cathepsin D-negative. Thus, cathepsin D may provide an indicator for appropriate intensive follow-up and adjuvant chemotherapy.
Gut and Liver 01/2014; 8(1):13-23. DOI:10.5009/gnl.2014.8.1.13 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer-related inflammation affects many aspects of malignancy. We confirm the effects of early postoperative systemic inflammation on cancer prognosis.
Six hundred consecutive patients underwent surgery for colorectal cancer from 2006 to 2009. Measurements of white blood cells, neutrophils, lymphocytes, monocytes, and platelet counts were performed preoperatively, daily until the fourth postoperative day, and subsequently every two days. Patients were divided into three groups based on the days spent on the leukocyte count to drop below 10,000/mm(3) after surgery.
Preoperative white blood cell (WBC) counts correlated with stage of disease. In univariate survival analyses, tumor, node, metastasis (TNM) stage, and monocyte count were associated with cancer-free survival. In addition, cancer-free survival outcomes were worse in patients who required more than four days for the normalization of WBC count. A TNM stage greater than II and the neutrophil lymphocyte ratio were associated with the duration of overall survival. In a multivariate analysis of these significant variables, TNM stage, an interval longer than four days for normalization of WBC counts and monocyte count independently associated with cancer-free survival.
Postoperative early inflammatory phase and preoperative monocyte count correlate with poor colon cancer prognosis. We can conclude that preoperative and postoperative inflammatory response and period unfavorably affect the metastatic microenvironment.
Cancer Research and Treatment 01/2014; 46(1):65-73. DOI:10.4143/crt.2014.46.1.65 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic appendectomy is a common procedure for treatment of appendicitis. However, in some complicated cases, like periappendiceal abscess, deciding on treatment options is very challenging. Early appendectomy or interval appendectomy may be possible, but remains controversial.