PURPOSE: Regional lymph node (LN) metastases are detected in 57-85% of patients with papillary thyroid carcinoma (PTC) and are associated with increased tumor recurrence. However, the management of lymphatic disease in patients with PTC has been ongoing source of debate. We have prospectively assessed the usefulness and accuracy of sentinel LN (SLN) biopsy for the detection of LN metastases in patients with PTC on preoperative imaging using single photon emission computed tomography/computed tomography (SPECT/CT) and 99mTc phytate. METHODS: We prospectively assessed 39 patients with PTC who had risk factors for recurrence or with the necessity of intraoperative LN sampling for suspicious LN metastases on preoperative imaging from August 2010 to March 2011. The patients underwent preoperative lymphoscintigraphy and SPETC/CT and intraoperative SLN biopsy (SLNB). RESULTS: 99mTc lymphoscintigraphy and SPECT/CT localized SLN in 38 patients (97.4%), with the gamma probe identifying 2.15 mean SLNs in the lateral neck of the 39 patients. Skip metastasis was found in one patient, and lateral compartment LN metastasis in 17 (43.5%). The sensitivity, specificity, and accuracy of SLNB for lateral compartment LN metastasis were 88.2%, 100%, and 94.8%, respectively. SLNB was more accurate and useful for lateral than for central compartment LN metastasis. CONCLUSION: SPECT/CT improved SLN detection and anatomical localization compared with lymphoscintigraphy. SLNB in patients with risk factors for recurrence or the necessity of intraoperative LN sampling for suspected LN metastases on preoperative imaging was accurate in detecting LN metastases and may help in deciding whether to perform lateral compartment dissection in patients with PTC.
Biopsy ; Carcinoma ; Factor IX ; Humans ; Lymph Nodes ; Lymphatic Diseases ; Lymphoscintigraphy ; Neck ; Neoplasm Metastasis ; Nitriles ; Phytic Acid ; Prospective Studies ; Pyrethrins ; Recurrence ; Risk Factors ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy ; Thyroid Gland ; Thyroid Neoplasms ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

PURPOSE: If cholesterol in the cell membrane is depleted by treating cells with methyl-beta-cyclodextrin (MbetaCD), the activities of transmembrane receptors are altered in a cell-specific and/or receptor-specific manner. The proinflammatory cytokines, IL-1beta is potent inducers of MUC5AC mRNA and protein synthesis in human airway epithelial cells. Cells activated by IL-1beta showed increased phosphorylation of extracellular signal regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). Thus, we investigated the effects of cholesterol depletion on the expression of MUC5AC in human airway epithelial cells and whether these alterations to MUC5AC expression were related to MAPK activity. MATERIALS AND METHODS: After NCI-H292 cells were pretreated with 1% MbetaCD before adding IL-1beta for 24 hours, MUC5AC mRNA expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and real time-PCR. Cholesterol depletion by MbetaCD was measured by modified microenzymatic fluorescence assay and filipin staining. The phosphorylation of IL-1 receptor, ERK and p38 MAPK, was analyzed by western blot. RESULTS: Cholesterol in the cell membrane was significantly depleted by treatment with MbetaCD on cells. IL-1beta-induced MUC5AC mRNA expression was decreased by MbetaCD and this decrease occurred IL-1-receptor-specifically. Moreover, we have shown that MbetaCD suppressed the activation of ERK1/2 and p38 MAPK in cells activated with IL-1beta. This result suggests that MbetaCD-mediated suppression of IL-1beta-induced MUC5AC mRNA operated via the ERK- and p38 MAPK-dependent pathway. CONCLUSION: Cholesterol depletion in NCI-H292 cell membrane may be considered an anti-hypersecretory method since it effectively inhibits mucus secretion of respiratory epithelial cells.
Cell Membrane/drug effects/*metabolism ; Cholesterol/*metabolism ; Epithelial Cells/metabolism ; Gene Expression ; Humans ; Mucin 5AC/genetics/*metabolism ; Respiratory System/*metabolism/pathology ; beta-Cyclodextrins/pharmacology

BACKGROUND: AND PURPOSE: To compare the characteristics of neuropathic pain in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: From 2016 to 2018, 500 patients with NMOSD and MS from 6 referral hospitals in Korea underwent pain investigation. After the patients with current pain were matched for sex ratio and disease duration as confounding factors, PainDETECT questionnaires were assessed in 99 NMOSD and 58 MS patients to investigate neuropathic pain. The short form of the Brief Pain Inventory from 74 patients with neuropathic pain component was also analysed. RESULTS: According to the PainDETECT questionnaire, mechanical allodynia (p=0.014) and thermal hyperalgesia (p=0.011) were more severe in NMOSD patients than in MS patients. Strong involvements (score >3) of the pain in domains of tingling/prickling sensation (p=0.024), mechanical allodynia (p=0.027), sudden pain attacks (p=0.018), and thermal hyperalgesia (p=0.002) were significantly more frequent in NMOSD compared to MS patients. Among the patients experiencing pain with a neuropathic component, total pain-related interference (p=0.045) scores were significantly higher in NMOSD patients than in MS patients. In daily life, pain interfered with normal work (p=0.045) and relationships with other people (p=0.039) more often in NMOSD patients than in MS patients. Although pain medication was prescribed more frequently in NMOSD patients, the percentage of patients experiencing medication-related pain relief was lower in those patients. CONCLUSIONS The severity of neuropathic pain and the pain-related interference in daily life were greater in NMOSD patients than in MS patients. Individualized analgesic management should be considered based on a comprehensive understanding of neuropathic pain in these patients.

BACKGROUND: Our aim was to set reference intervals of healthy adults using Beckman Coulter LH 750 by gender and age. METHODS: The specimens were obtained from a total of 705 healthy adults (male 484, female 221), who took part in annual health-check at Chungnam National University Hospital, analyzed in total 22 parameters and compared using SPSS V10.0 program. RESULTS: Totally 16 parameters showed the Gaussian distribution with 12 in parametric method and 4 in logarithmically transformed parametric method. All acquired reference intervals were showed in Table 3, 4, 5 and 6. There were statistical significances between genders in RBC, Hgb, Hct, MCV, MCH, WBC, EO%, LY#, MO#, EO#, MPV, PDW (P<0.001), BA% (P=0.001), NE% (P=0.016), BA# (P=0.019), MO% (P=0.021) and NE# (P=0.039), between age decades in RBC, Hgb, Hct, MCV, MCH, NE%, LY% (P<0.001), LY# (P=0.002), EO%, NE# (P=0.003) and Pct (P=0.033) as well as between genders and age decades in RBC, Hct (P=0.001), Hgb (P=0.004), LY# (P=0.005), Plt (P=0.014) and MO% (P=0.017). CONCLUSIONS: This study suggested that the reference intervals of RBC and Hgb ought to be set by both genders and age decades, WBC by gender and the others by total study populations. Moreover, it need to be set the reference intervals by each laboratory for itself and to be monitored with periodic review.
Adult* ; Cell Count* ; Chungcheongnam-do ; Female ; Humans ; Normal Distribution

Background: Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial. Methods: Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks. Results: TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score. Conclusion Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

Background/Aims: The learning curve is essential in endoscopic submucosal dissection (ESD) training to improve outcomes and reduce the risk of procedure-related complications. We compared the outcomes of gastric ESD in live pigs performed by inexperienced endoscopists with or without ex vivo training. Materials and Methods: At the Olympus Medical Training and Education Center, nine endoscopists inexperienced in ESD were randomly divided into two groups (group A: ex vivo training followed by in vivo training; group B: in vivo training only), and they performed gastric ESDs. Results: A total of 18 ESDs were performed. The en bloc resection rate was 88.9% (16/18), and the complete resection rate was 94.4% (17/18). The median specimen size was 2.5 cm in group A and 2.1 cm in group B (P=0.227). There was no significant difference in the procedure time between the two groups, except for the marking time (0′58″ vs. 2′58″, P=0.027). However, group A took a shorter time in dissecting the same area than group B (109 vs. 246 sec/cm2, P=0.083). Complication rates were not significantly different between both groups. Conclusions The procedure time during in vivo ESD training in pigs may be shortened by prior ex vivo training. However, the ex vivo model presented poor air inflation, unstable fixation, and excessive mucosal hardness for cutting. An advanced simulator or sufficient ex vivo training may be effective in training for the ESD procedure.

Background/Aims: The learning curve is essential in endoscopic submucosal dissection (ESD) training to improve outcomes and reduce the risk of procedure-related complications. We compared the outcomes of gastric ESD in live pigs performed by inexperienced endoscopists with or without ex vivo training. Materials and Methods: At the Olympus Medical Training and Education Center, nine endoscopists inexperienced in ESD were randomly divided into two groups (group A: ex vivo training followed by in vivo training; group B: in vivo training only), and they performed gastric ESDs. Results: A total of 18 ESDs were performed. The en bloc resection rate was 88.9% (16/18), and the complete resection rate was 94.4% (17/18). The median specimen size was 2.5 cm in group A and 2.1 cm in group B (P=0.227). There was no significant difference in the procedure time between the two groups, except for the marking time (0′58″ vs. 2′58″, P=0.027). However, group A took a shorter time in dissecting the same area than group B (109 vs. 246 sec/cm2, P=0.083). Complication rates were not significantly different between both groups. Conclusions The procedure time during in vivo ESD training in pigs may be shortened by prior ex vivo training. However, the ex vivo model presented poor air inflation, unstable fixation, and excessive mucosal hardness for cutting. An advanced simulator or sufficient ex vivo training may be effective in training for the ESD procedure.

Background: Endoscopic surveillance after total gastrectomy (TG) for gastric cancer is routinely performed to detect tumor recurrence and postoperative adverse events.However, the reports on the clinical benefits of endoscopic surveillance are ambiguous. We investigated the clinical benefit of endoscopic surveillance after TG for gastric cancer. Methods: We analyzed 848 patients who underwent TG with R0 resection for gastric cancer between 2011 and 2012 (380 early gastric cancer and 468 advanced gastric cancer) and underwent regular postoperative surveillance with endoscopy and abdominopelvic computed tomography (CT) with contrast. Results: Median follow-up periods were 58 months for both endoscopy (range, 3–96) and abdominopelvic CT (range, 1–96). Tumor recurrence occurred in 167 patients (19.7%), of whom seven (4.2%) were locoregional recurrences in the peri-anastomotic area (n = 5) or regional gastric lymph nodes (n = 2). Whereas the peri-anastomotic recurrences were detected by both endoscopy and abdominopelvic CT, regional lymph node recurrences were only detected by abdominopelvic CT. Out of the 23 events of postoperative adverse events, the majority (87%) were detected by radiologic examinations; three events of benign strictures in the anastomotic site were detected only by endoscopy. Conclusion Endoscopic surveillance did not have a significant role in detecting locoregional tumor recurrence and postoperative adverse events after TG with R0 resection for gastric cancer. Routine endoscopic surveillance after TG may be considered optional and performed according to the capacities of each clinical setting.

Background: Endoscopic surveillance after total gastrectomy (TG) for gastric cancer is routinely performed to detect tumor recurrence and postoperative adverse events.However, the reports on the clinical benefits of endoscopic surveillance are ambiguous. We investigated the clinical benefit of endoscopic surveillance after TG for gastric cancer. Methods: We analyzed 848 patients who underwent TG with R0 resection for gastric cancer between 2011 and 2012 (380 early gastric cancer and 468 advanced gastric cancer) and underwent regular postoperative surveillance with endoscopy and abdominopelvic computed tomography (CT) with contrast. Results: Median follow-up periods were 58 months for both endoscopy (range, 3–96) and abdominopelvic CT (range, 1–96). Tumor recurrence occurred in 167 patients (19.7%), of whom seven (4.2%) were locoregional recurrences in the peri-anastomotic area (n = 5) or regional gastric lymph nodes (n = 2). Whereas the peri-anastomotic recurrences were detected by both endoscopy and abdominopelvic CT, regional lymph node recurrences were only detected by abdominopelvic CT. Out of the 23 events of postoperative adverse events, the majority (87%) were detected by radiologic examinations; three events of benign strictures in the anastomotic site were detected only by endoscopy. Conclusion Endoscopic surveillance did not have a significant role in detecting locoregional tumor recurrence and postoperative adverse events after TG with R0 resection for gastric cancer. Routine endoscopic surveillance after TG may be considered optional and performed according to the capacities of each clinical setting.

BACKGROUND/AIMS: C-reactive protein (CRP) is a serologic activity marker in Crohn's disease (CD), but it may be less useful in evaluating CD activity in ileal CD patients. We aimed to investigate the usefulness of CRP as a disease activity marker in CD according to disease location. METHODS: Korean CD patients in a single hospital were evaluated. Factors associated with elevated CRP concentration at the time of diagnosis of CD and the association between the physician's prediction regarding upcoming surgery and the sites of the lesions directly related to surgery were analyzed. RESULTS: Of 435 CD patients, 25.7%, 6.9%, and 67.4% had ileal, colonic, and ileocolonic CD, respectively. Multivariate analysis revealed that an elevated erythrocyte sedimentation rate, reduced serum albumin, CD activity index (CDAI) >220, and ileocolonic/colonic location were associated with an elevated CRP level and that the CRP level was significantly correlated with the CDAI in all CD patients (gamma=0.466, p<0.01). However, the correlation coefficient was dependent on the location, with values of 0.395, 0.456, and 0.527 in patients with an ileal, ileocolonic, and colonic disease location, respectively. Surgery for ileal lesions was less predictable than surgery for ileocolonic or colonic lesions during follow-up. CONCLUSIONS: CRP is less useful as a disease activity marker in patients with ileal CD than those with ileocolonic or colonic CD.
Adolescent ; Adult ; Aged ; Biological Markers/blood ; Blood Sedimentation ; C-Reactive Protein/*analysis ; Child ; Colon/pathology ; Crohn Disease/blood/*diagnosis/pathology ; Female ; Humans ; Ileum/pathology ; Male ; Middle Aged ; Serum Albumin/analysis ; Severity of Illness Index ; Young Adult