Effect of Sedatives on In-hospital and Long-term Mortality of Critically Ill Patients Requiring Extended Mechanical Ventilation for ≥ 48 Hours

Background@#The purpose of this study was to assess the correlation between sedatives and mortality in critically ill patients who required mechanical ventilation (MV) for ≥ 48 hours from 2008 to 2016. @*Methods@#We conducted a nationwide retrospective cohort study using population-based healthcare reimbursement claims database. Data from adult patients (aged ≥ 18) who underwent MV for ≥ 48 hours between 2008 and 2016 were identified and extracted from the National Health Insurance Service database. The benzodiazepine group consisted of patients who were administered benzodiazepines for sedation during MV. All other patients were assigned to the non-benzodiazepine group. @*Results@#A total of 158,712 patients requiring MV for ≥ 48 hours were admitted in 55 centers in Korea from 2008 to 2016. The benzodiazepine group had significantly higher in-hospital and one-year mortality compared to the non-benzodiazepine group (37.0% vs. 34.3%, 55.0% vs. 54.4%, respectively). Benzodiazepine use decreased from 2008 to 2016, after adjusting for age, sex, and mean Elixhauser comorbidity index in the Poisson regression analysis (incidence rate ratio, 0.968; 95% confident interval, 0.954–0.983; P < 0.001). Benzodiazepine use, older age, lower case volume (≤ 500 cases/year), chronic kidney disease, and higher Elixhauser comorbidity index were common significant risk factors for in-hospital and oneyear mortality. @*Conclusion@#In critically ill patients undergoing MV for ≥ 48 hour, the use of benzodiazepines for sedation, older age, and chronic kidney disease were associated with higher in-hospital mortality and one-year mortality. Further studies are needed to evaluate the impact of benzodiazepines on the mortality in elderly patients with chronic kidney disease requiring MV for ≥ 48 hours.

Effect of Sedatives on In-hospital and Long-term Mortality of Critically Ill Patients Requiring Extended Mechanical Ventilation for ≥ 48 Hours

Background@#The purpose of this study was to assess the correlation between sedatives and mortality in critically ill patients who required mechanical ventilation (MV) for ≥ 48 hours from 2008 to 2016. @*Methods@#We conducted a nationwide retrospective cohort study using population-based healthcare reimbursement claims database. Data from adult patients (aged ≥ 18) who underwent MV for ≥ 48 hours between 2008 and 2016 were identified and extracted from the National Health Insurance Service database. The benzodiazepine group consisted of patients who were administered benzodiazepines for sedation during MV. All other patients were assigned to the non-benzodiazepine group. @*Results@#A total of 158,712 patients requiring MV for ≥ 48 hours were admitted in 55 centers in Korea from 2008 to 2016. The benzodiazepine group had significantly higher in-hospital and one-year mortality compared to the non-benzodiazepine group (37.0% vs. 34.3%, 55.0% vs. 54.4%, respectively). Benzodiazepine use decreased from 2008 to 2016, after adjusting for age, sex, and mean Elixhauser comorbidity index in the Poisson regression analysis (incidence rate ratio, 0.968; 95% confident interval, 0.954–0.983; P < 0.001). Benzodiazepine use, older age, lower case volume (≤ 500 cases/year), chronic kidney disease, and higher Elixhauser comorbidity index were common significant risk factors for in-hospital and oneyear mortality. @*Conclusion@#In critically ill patients undergoing MV for ≥ 48 hour, the use of benzodiazepines for sedation, older age, and chronic kidney disease were associated with higher in-hospital mortality and one-year mortality. Further studies are needed to evaluate the impact of benzodiazepines on the mortality in elderly patients with chronic kidney disease requiring MV for ≥ 48 hours.

Proposal of a New TNM Classification for Gastric Cancer: Focusing on pN3b and Cytology-Positive (CY1) Disease

PURPOSE: Gastric cancer with lymph node metastasis (LNM) more than 15 (N3b) was defined as stage IV until the 6th AJCC system. However, it has been reclassified as a localized disease (stage IIb or III) since the 7th system. The aim of this study is to demonstrate that the survival of N3b is comparable to cytology-only positive (CY1-only) stage IV and to propose a new TNM system interpreting N3b as an eligibility criterion for receiving more intensive chemotherapy regimens. MATERIALS AND METHODS: 1,430 patients who underwent gastric cancer surgery at Seoul National University Hospital from 2007 to 2012 were retrospectively analyzed. The 5-year survival rate (5YSR) and 3-year recurrence-free survival (RFS) were evaluated according to the 7th and 8th systems, as well as a new categorization based on N-classification; N0-2 (LNM15). RESULTS: The survival of N3b is comparable to that of CY1-only stage IV (log rank test, P=0.671) and is distinct from that of grossly stage IV (log rank test, P<0.001). The survival of the remaining stage IIIc (T4bN3a) was comparable to those of N3b and CY1-only stage IV. Most N3b patients had significantly shorter 3-year RFS and mean RFS than those with IIb–IIIc, as if N3b itself was a higher TNM stage. CONCLUSIONS: In terms of survival, T4bN3a, N3b, and CY1-only stage IV were unified as stage IVa, while grossly stage IV was defined as stage IVb. N3b can be regarded as an eligibility criterion for undergoing more intensive chemotherapy regimens.

Effect of Institutional Case Volume on In-Hospital and Long-Term Mortality in Critically Ill Patients Requiring Mechanical Ventilation for 48 Hours or More

BACKGROUND: The purpose of this study was to evaluate whether institutional case volume affects clinical outcomes in patients receiving mechanical ventilation for 48 hours or more. METHODS: We conducted a nationwide retrospective cohort study using the database of Korean National Healthcare Insurance Service. Between January 2007 and December 2016, 158,712 adult patients were included at 55 centers in Korea. Centers were categorized according to the average annual number of patients: > 500, 500 to 300, and 500 patients/year) showed lower in-hospital mortality and long-term mortality, compared to centers with lower case volume (< 300 patients/year) in patients who required mechanical ventilation for 48 hours or more.

Pylorus-Preserving Gastrectomy for Gastric Cancer

Pylorus-preserving gastrectomy (PPG) is a function-preserving surgery for the treatment of early gastric cancer (EGC), aiming to decrease the complication rate and improve postoperative quality of life. According to the Japanese gastric cancer treatment guidelines, PPG can be performed for cT1N0M0 gastric cancer located in the middle-third of the stomach, at least 4.0 cm away from the pylorus. Although the length of the antral cuff gradually increased, from 1.5 cm during the initial use of the procedure to 3.0 cm currently, its optimal length still remains unclear. Standard procedures for the preservation of pyloric function, infra-pyloric vessels, and hepatic branch of the vagus nerve, make PPG technically more difficult and raise concerns about incomplete lymph node dissection. The short- and long-term oncological and survival outcomes of PPG were comparable to those for distal gastrectomy, but with several advantages such as a lower incidence of dumping syndrome, bile reflux, and gallstone formation, and improved nutritional status. Gastric stasis, a typical complication of PPG, can be effectively treated by balloon dilatation and stent insertion. Robot-assisted pylorus-preserving gastrectomy is feasible for EGC in the middle-third of the stomach in terms of the short-term clinical outcome. However, any benefits over laparoscopy-assisted PPG (LAPPG) from the patient's perspective have not yet been proven. An ongoing Korean multicenter randomized controlled trial (KLASS-04), which compares LAPPG and laparoscopy-assisted distal gastrectomy for EGC in the middle-third of the stomach, may provide more clear evidence about the advantages and oncologic safety of PPG.

Intracranial hemorrhage induced uncontrolled seizure in a deceased donor liver transplant patient: a case report / 대한마취과학회지

Seizure is the second most common neurologic complication after liver transplantation and may be caused by metabolic abnormalities, electrolyte imbalance, infection, and immunosuppressant toxicity. A 61-year-old male patient underwent liver transplantation due to hepatitis B virus-related liver cirrhosis with portal systemic encephalopathy. The immediate postoperative course of the patient was uncomplicated. However, on postoperative day (POD) 6, weakness developed in both lower extremities. No abnormal findings were detected on a brain computed tomography (CT) scan on POD 8, but a generalized tonic clonic seizure developed which was difficult to control even with multiple antiepileptic drugs. A follow-up brain CT scan on POD 15 showed a 2.7 cm sized acute intracranial hemorrhage (ICH) in the left parietal lobe. The patient's mental status improved after 2 months and he was able to communicate through eye blinking or head shaking. Our case reports an acute ICH that manifested into a refractory seizure in a patient who underwent a liver transplant.

Sepsis in Patients Receiving Immunosuppressive Drugs in Korea: Analysis of the National Insurance Database from 2009 to 2013 / 대한중환자의학회지

BACKGROUND: The aim of this study is to evaluate the influence of immunosuppressants on in-hospital mortality from sepsis. METHODS: Using data of the Health Insurance Review & Assessment Service, we collected data from patients who were admitted to the hospital due to sepsis from 2009 to 2013. Based on drugs commonly used for immunosuppression caused by various diseases, patients were divided into three groups; immunosuppressant group, steroid-only group, and control group. Patients with no history of immunosuppressants or steroids were assigned to the control group. To identify risk factors of in-hospital mortality in sepsis, we compared differences in patient characteristics, comorbidities, intensive care unit (ICU) care requirements, and immunodeficiency profiles. Subgroup analysis according to age was also performed. RESULTS: Of the 185,671 included patients, 13,935 (7.5%) were in the steroid-only group and 2,771 patients (1.5%) were in the immunosuppressant group. The overall in-hospital mortality was 38.9% and showed an increasing trend with age. The steroid-only group showed the lowest in-hospital mortality among the three groups except the patients younger than 30 years. The steroid-only group and immunosuppressant group received ICU treatment more frequently (p < 0.001), stayed longer in the hospital (p < 0.001), and showed higher medical expenditure (p < 0.001) compared to the normal group. Univariate and multivariate analyses revealed that age, male gender, comorbidities (especially malignancy), and ICU treatment had a significant effect on in-hospital mortality. CONCLUSIONS: Despite longer hospital length of stay and more frequent need for ICU care, the in-hospital mortality was lower in patients taking immunosuppressive drugs than in patients not taking immunosuppressive drugs.

Clinical Outcome of Modified Laparoscopy-Assisted Proximal Gastrectomy Compared to Conventional Proximal Gastrectomy or Total Gastrectomy for Upper-Third Early Gastric Cancer with Special References to Postoperative Reflux Esophagitis

PURPOSE: This study evaluated the functional and oncological outcomes of proximal gastrectomy (PG) in comparison with total gastrectomy (TG) for upper-third early gastric cancer (EGC). MATERIALS AND METHODS: The medical records of upper-third EGC patients who had undergone PG (n=192) or TG (n=157) were reviewed. The PG group was further subdivided into patients who had undergone conventional open PG (cPG; n=157) or modified laparoscopy-assisted PG (mLAPG; n=35). Patients who had undergone mLAPG had a longer portion of their intra-abdominal esophagus preserved than patients who had undergone cPG. Surgical morbidity, recurrence, long-term nutritional status, and the incidence of reflux esophagitis were compared between the groups. RESULTS: The rate of postoperative complications was significantly lower for PG than TG (16.7% vs. 31.2%), but the five-year overall survival rate was comparable between the two groups (99.3% vs. 96.3%). Postoperative levels of hemoglobin and albumin were significantly higher for patients who had undergone PG. However, the incidence of reflux esophagitis was higher for PG than for TG (37.4% vs. 3.7%; P<0.001). mLAPG was related to a lower incidence of reflux esophagitis after PG (P<0.001). CONCLUSIONS: Compared to TG, PG showed an advantage in terms of postoperative morbidity and nutrition, and there was a comparable prognosis between the two procedures. Preserving the intra-abdominal esophagus may lower the incidence of reflux esophagitis associated with PG.

Sepsis in Patients Receiving Immunosuppressive Drugs in Korea: Analysis of the National Insurance Database from 2009 to 2013 / 대한구급학회지

BACKGROUND: The aim of this study is to evaluate the influence of immunosuppressants on in-hospital mortality from sepsis. METHODS: Using data of the Health Insurance Review & Assessment Service, we collected data from patients who were admitted to the hospital due to sepsis from 2009 to 2013. Based on drugs commonly used for immunosuppression caused by various diseases, patients were divided into three groups; immunosuppressant group, steroid-only group, and control group. Patients with no history of immunosuppressants or steroids were assigned to the control group. To identify risk factors of in-hospital mortality in sepsis, we compared differences in patient characteristics, comorbidities, intensive care unit (ICU) care requirements, and immunodeficiency profiles. Subgroup analysis according to age was also performed. RESULTS: Of the 185,671 included patients, 13,935 (7.5%) were in the steroid-only group and 2,771 patients (1.5%) were in the immunosuppressant group. The overall in-hospital mortality was 38.9% and showed an increasing trend with age. The steroid-only group showed the lowest in-hospital mortality among the three groups except the patients younger than 30 years. The steroid-only group and immunosuppressant group received ICU treatment more frequently (p < 0.001), stayed longer in the hospital (p < 0.001), and showed higher medical expenditure (p < 0.001) compared to the normal group. Univariate and multivariate analyses revealed that age, male gender, comorbidities (especially malignancy), and ICU treatment had a significant effect on in-hospital mortality. CONCLUSIONS: Despite longer hospital length of stay and more frequent need for ICU care, the in-hospital mortality was lower in patients taking immunosuppressive drugs than in patients not taking immunosuppressive drugs.

The Effect of Combined Enteral and Parenteral Nutrition for Anastomotic Leakage after Gastric Cancer Surgery

PURPOSE: The effectiveness of enteral nutrition for patients with anastomotic leakage after gastric cancer surgery is controversial. The purpose of this study is to compare effectiveness between combined enteral nutrition with parenteral nutrition (EPN) and total parenteral nutrition (TPN). METHODS: Patients who underwent gastric cancer surgery for primary gastric cancer from April 2010 to August 2012 were reviewed. Clinicopathologic characteristics, complication, laboratory tests, and body weight (Bwt) were compared between EPN and PN. RESULTS: Among patients with postoperative leakage within postoperative 1 month (n=43), 13 patients were supported by EPN and 23 patients by TPN. Clinicopathologic characteristics, including preoperative Bwt, body mass index, nutritional status, other complications, and TNM stage were similar. Preoperative serum albumin and Bwt were similar between EPN and TPN. However, after 1 week of nutritional support, albumin at EPN was significantly higher than that of PN (3.52+/-0.3 and 3.25+/-0.3; P=0.010). Adjusted by preoperative Bwt, preoperative nutritional status, and difference in Bwt between preoperative and pre-nutritional support period, decrease of Bwt between pre-nutritional support and discharge was significantly less at EPN than at TPN (-4.5+/-5.4% and -6.3+/-4.1%; P=0.001). CONCLUSION: In terms of the maintenance of serum albumin and Bwt during nutritional support, EPN may be a better supportive option than TPN for patients with anastomotic leakage after gastric cancer surgery.

The Value of Postoperative Serum Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 Levels for the Early Detection of Gastric Cancer Recurrence after Curative Resection

PURPOSE: This study aimed to evaluate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels to detect gastric cancer recurrence. MATERIALS AND METHODS: We retrospectively reviewed 154 patients who developed recurrence within 2 years after curative gastric cancer surgery and analyzed the relationship between postoperative CEA and CA19-9 levels and recurrence. We readjusted the cut-off values to improve the detection of recurrence. Subgroup analysis according to clinicopathologic variables was performed to further investigate the relationship between recurrence and CEA and CA19-9 levels. RESULTS: The sensitivity and specificity for elevated CEA levels to detect recurrence were 40.6% and 89.5%, respectively, and those for CA19-9 were 34.2% and 93.6%, respectively. The sensitivity and specificity for elevation of either tumor marker were 54.3% and 84.0%, respectively; those for elevation of both tumor markers were 19.2% and 98.4%, respectively. By readjusting the cut-off values from 5.0 ng/ml to 5.2 ng/ml for CEA and from 37.00 U/ml to 30.0 U/ml for CA19-9, the sensitivity was increased from 34.2% to 40.2% for CA19-9, while there was no increase in sensitivity for CEA. In subgroup analysis, the sensitivity of CEA was higher in patients with elevated preoperative CEA levels than in patients with normal preoperative CEA levels (86.7% versus 33.7%; P<0.001). Furthermore, the sensitivity of CA19-9 was higher in patients with elevated preoperative CA19-9 levels than in patients with normal preoperative CA19-9 levels (82.61% versus 26.83%; P<0.001). CONCLUSIONS: CEA and/or CA19-9 measurement with the readjusted cut-off values allows for more effective detection of gastric cancer recurrence.

Effects of Screening on Gastric Cancer Management: Comparative Analysis of the Results in 2006 and in 2011

PURPOSE: This study aimed to analyze the effect of screening by using endoscopy on the diagnosis and treatment of gastric cancer. MATERIALS AND METHODS: The clinicopathologic characteristics of gastric cancer were compared in individuals who underwent an endoscopy because of symptoms (non-screening group) or for screening purposes (screening group). The distributions of gastric cancer stages and treatment modalities in 2006 and 2011 were compared. RESULTS: The proportion of patients in the screening group increased from 45.1% in 2006 to 65.4% in 2011 (P<0.001). The proportion of stage I cancers in the entire patient sample also increased (from 60.5% in 2006 to 70.6% in 2011; P=0.029). In 2011, the percentages of patients with cancer stages I, II, III, and IV were 79.9%, 8.2%, 10.9%, and 1.1%, respectively, in the screening group, and 47.9%, 10.8%, 29.8%, and 11.5%, respectively, in the non-screening group. The proportion of laparoscopic and robotic surgeries increased from 9.6% in 2006 to 48.3% in 2011 (P<0.001), and endoscopic submucosal dissection increased from 9.8% in 2006 to 19.1% 2011 (P<0.001). CONCLUSIONS: The proportion of patients diagnosed with gastric cancer by using the screening program increased between 2006 and 2011. This increase was associated with a high proportion of early-stage cancer diagnoses and increased use of minimally invasive treatments.

Laparoscopic Repair of Large Bladder Herniation Presenting as an Inguinal Hernia

The bladder is involved in 1% to 3% of all hernia cases. We report a case of a large paraperitoneal bladder hernia (BH) in a 59-year-old man who had a palpable scrotal mass. Several techniques and approaches have been described for managing BHs. We performed a laparoscopic partial cystectomy and herniorrhaphy. This is the first case report on the repair of a large BH by use of a laparoscopic technique in Korea.

Clinical Significance of Protocol Biopsy Soon after Renal Transplantation / 대한이식학회지

BACKGROUND: Several studies reported that sub-clinical rejection (SCR) detected by a protocol biopsy soon after renal transplantation does permanent damage to a renal allograft, contributing to chronic allograft nephropathy (CAN). This article investigated the risk factors involved in SCR and the effects of treating SCR, and evaluated the clinical significance of a protocol biopsy soon after renal transplantation. METHODS: From January 2007 to June 2010, 253 patients received renal transplantation. Patients were divided into two groups according to whether or not they had undergone a protocol biopsy. To analyze the effect of SCR treatments, patients who were diagnosed with SCR were divided into two groups according to whether or not they had been treated with SCR. The patients who did not undertake a protocol biopsy were included in the untreated groups. RESULTS: Among 138 patients who undertook protocol biopsies, 65 patients (47.1%) showed SCR. In univariate analysis, both the number of HLA-DR mismatches (P=0.003) and not using Simulect (P=0.01) were identified as risk factors of SCR. In multivariate analysis, not using Simulect (P=0.006) was identified as an risk factor independent of SCR. deltaGFR, subtracting GFR at 1 week from GFR at that point, showed significant differences between SCR-treated patients and untreated patients at 1, 3, 6, 9, 12, 24, and 36 months with a P value of less than 0.05. CONCLUSIONS: A protocol biopsy can detect SCR, especially in patients with risk factors such as a high number of HLA mismatches or not using Simulect. Treatment of SCR detected by protocol biopsy will help to improve long-term renal function.

Clinical Significance of Protocol Biopsy Soon after Renal Transplantation / 대한이식학회지

BACKGROUND: Several studies reported that sub-clinical rejection (SCR) detected by a protocol biopsy soon after renal transplantation does permanent damage to a renal allograft, contributing to chronic allograft nephropathy (CAN). This article investigated the risk factors involved in SCR and the effects of treating SCR, and evaluated the clinical significance of a protocol biopsy soon after renal transplantation. METHODS: From January 2007 to June 2010, 253 patients received renal transplantation. Patients were divided into two groups according to whether or not they had undergone a protocol biopsy. To analyze the effect of SCR treatments, patients who were diagnosed with SCR were divided into two groups according to whether or not they had been treated with SCR. The patients who did not undertake a protocol biopsy were included in the untreated groups. RESULTS: Among 138 patients who undertook protocol biopsies, 65 patients (47.1%) showed SCR. In univariate analysis, both the number of HLA-DR mismatches (P=0.003) and not using Simulect (P=0.01) were identified as risk factors of SCR. In multivariate analysis, not using Simulect (P=0.006) was identified as an risk factor independent of SCR. deltaGFR, subtracting GFR at 1 week from GFR at that point, showed significant differences between SCR-treated patients and untreated patients at 1, 3, 6, 9, 12, 24, and 36 months with a P value of less than 0.05. CONCLUSIONS: A protocol biopsy can detect SCR, especially in patients with risk factors such as a high number of HLA mismatches or not using Simulect. Treatment of SCR detected by protocol biopsy will help to improve long-term renal function.

Pyoderma Gangranosum of the Penis

We report a patient who developed pyoderma gangrenosum in the penis with invasion of the distal urethra. The patient was treated with prednisolone and thalidomide, followed by a reconstructive surgical repair using a scrotal island flap. We report this case with a brief review of the literature.

Granulocyte Macrophage Colony-Stimulating Factor May Modulate the Post-transcription Pathway of Interleukin-6 Expression in Prostate Carcinoma Cells

Interleukin-6 (IL-6) can stimulate a variety of tumors including prostatic carcinoma. Research has recently shown that IL-6 may act to stimulate the progression of prostatic cancer. To date, little research has been performed to better understand the nature of granulocyte macrophage colony-stimulating factor (GM-CSF) and the expression of IL-6. The aim of this study was to evaluate the effects of GM-CSF on the expression of IL-6 in prostate cancer-3 (PC-3) cells. The bone-derived PC-3 cell line was used in this study. Reverse transcription polymerase chain reaction (RT-PCR) and real- time PCR were performed to detect IL-6 mRNA expression. The IL-6 protein was measured by enzyme-linked immunosorbent assay (ELISA) after treatment with hGM-CSF. Our data indicated that IL-6 mRNA expression did not increase after treatment with hGM-CSF in comparison to the control group. However, the expression of IL-6 protein was increased compared to the control group. GM-CSF may modulate the post-transcription pathway of IL-6 expression in prostate carcinoma cells. Our data suggest that GM-CSF may have a role in IL-6-mediated development of prostate cancer.

The Effect of Tamsulosin on Expulsion of Ureteral Stones after Extracorporeal Shock Wave Lithotripsy / 대한비뇨기과학회지

PURPOSE: The aim of this study was to evaluate the effect of tamsulosin on expulsion of ureteral stones after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: Seventy-six patients(39 with upper ureteral stones and 37 with lower ureteral stones) treated with ESWL for stones <10mm were randomly divided into two groups. Tamsulosin(0.2mg orally once daily) was administered to group 1; group 2 received no medications. All patients were evaluated with respect to the number of episodes of ureteral colic, the expulsion rates of stones after ESWL, and the mean number of sessions of ESWL until complete expulsion of stones. RESULTS: The complete expulsion rates of upper and lower ureteral stones did not differ significantly between groups 1 and 2 during each session of ESWL; however, the mean session of ESWL was lower in group 1 than in group 2. For upper ureteral stones, 1.8 sessions were necessary per patient in group 1, while 2.3 sessions were required for the patients in group 2(p=0.039). For lower ureteral stones, 2.0 sessions were necessary per patient in group 1, while 2.9 sessions were required for the patients in group 2(p=0.032). There were significant decreases in the number of episodes of pain in group 1 with lower ureteral stones(p=0.014). There were no side effects associated with tamsulosin. CONCLUSIONS: The use of tamsulosin in the treatment of upper and lower ureteral stones after ESWL can decrease the mean number of sessions of ESWL and the number of episodes of pain, but cannot improve the expulsion rate. Further research regarding the cost-effectiveness of tamsulosin after ESWL is needed.

Eta-1/Osteopontin Genetic Polymorphism is Associated with Urolithiasis in Koreans / 대한비뇨기과학회지

PURPOSE: Osteopontin(OPN) is one of the major non-collagenous bone matrix proteins produced by osteoblasts and osteolclasts, and it is also involved in the pathogenesis of urolithiasis. Single nucleotide polymorphisms(SNPs), as a tool for searching for the genetic markers of disease, have a large role in investigating the genetic markers of complex human diseases. The aim of this study is to investigate the association with this SNP at position nucleotide 9250(C-->T) in the OPN gene and the susceptibility to urolithiasis. We also compared the allele frequency of Koreans with those of Americans and Japanese. MATERIALS AND METHODS: A total of 161 urolithiasis patients and 104 healthy controls were studied. The SNPs located at position 9520 in the OPN gene were genotyped using restriction fragment length polymorphism(RFLP). The wild-type sequence contains a C while the polymorphism variant is a T(C-->T), which results in the appearance of an Alu I restriction site. RESULTS: The gene frequencies of C/C, C/T and T/T at position 9250 on the Eta-1/osteopontin gene in urolithiasis patients were 10.6%, 36.6% and 52.8%, respectively, compared with 6.7%, 27.9% and 65.8%, respectively, in the controls(p>0.05). The allele frequencies of C and T at this position in the urolithiasis patients were 28.9 and 72.1, respectively, whereas those in the controls were 20.7 and 79.3, respectively,(p<0.05). The allele frequencies found in the present study were compared with those coding SNPs described in the USA database; 60 and 39(USA) vs 20.7 and 79.3 (Korea), respectively(p<0.05). CONCLUSIONS: Those findings suggest there is no association of with Eta-1/osteopontin genetic polymorphism, but the allele frequencies were significantly associated with urolithiasis patients. We also observed difference of allele frequencies in our controls and in the USA controls and these differences may be caused by a difference in the incidence of urolithiasis patients between the two countries.

Effects of Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) on the Interleukin-6 Expression in the Prostate Cancer Cell Line PC-3 / 대한비뇨기과학회지

PURPOSE: Interleukin-6 (IL-6) can stimulate a variety of tumors including prostatic carcinoma. Research has recently shown that IL-6 may act to stimulate the progression of prostatic cancer. IL-6 is elevated in the sera of patients with metastatic prostatic cancer and it has been shown to be a candidate marker of disease activity. To date, little work has been performed to characterize the nature of granulocyte macrophage colony-stimulating factor (GM-CSF) and the expression of IL-6. The aim of this study is to evaluate the effects of GM-CSF on the expression of IL-6 in PC-3 cells. MATERIALS AND METHODS: The bone-derived PC-3 cell line was used in this study. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the GM-CSF and also the IL-6 mRNA expression. The IL-6 protein was measured by enzyme-linked immunosorbent assay (ELISA) after treatments with the hGM-CSF. RESULTS: hGM-CSF was expressed in the PC-3 cell line. Our data indicated that the IL-6 mRNA expression was not increased at 4, 8 and 12 hours by the hGM-CSF in comparison to the control group, but it was slightly increased at 24 and 48 hours. The expression of IL-6 protein was increased at 4, 8, 12, 24 and 48 hours after hGM-CSF treatment, in comparison with the control group. CONCLUSIONS: The IL-6 mRNA expression was slightly increased by hGM-CSF at 24 and 48 hours in comparison to the control group. Yet the IL-6 protein expression increased before the IL-6 mRNA expression. Therefore, hGM-CSF may modulate the post-transcription pathway of the IL-6 expression in prostate carcinoma cells. Our data suggest that GM-CSF may have a possible IL-6 mediated pathophysiologic role in prostate cancer.