Purpose: The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC).We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC. Materials and Methods: Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion. Results: LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low-(0–1 point), intermediate- (2–3 points), and high-risk (4–8 points), respectively (P-fortrend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001).In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015). Conclusions The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.

Background/Aims: The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC. Methods: This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated-type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories. Results: For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-tohigh risk category. No such differences were noted in the low-risk category. Conclusions The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.

BACKGROUND/AIMS: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. METHODS: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed. RESULTS: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3–4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001). CONCLUSIONS Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.
Cohort Studies ; Coronavirus ; Coronavirus Infections* ; Follow-Up Studies ; Humans ; Korea ; Middle East* ; Pneumonia* ; Prospective Studies ; Survivors

BACKGROUND: We evaluated the outcomes of serum galactomannan (GM) assay for the screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients while on primary antifungal prophylaxis (PAP). METHODS: This study included patients with hematologic disorders who underwent alloHSCT from January 2013 to November 2015. Patients received routine PAP with fluconazole before 2014 and micafungin after 2014; serum GM tests were performed and retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum GM tests for detection of probable/proven IPA were evaluated. The serial change of serum GM levels was illustrated on a time series plot. RESULTS: A total of 136 alloHSCT recipients at Seoul National University Hospital were included in the study. Fluconazole was administered in 72 patients for PAP, while micafungin was administered in the remaining 64 patients. The overall sensitivity, specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI] 78.9–99.9%), 93.8% (95% CI 91.7–95.5%), and 99.8% (95% CI 99.1–100.0%), respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI 23.9–48.2%). The serial change in serum GM levels differed according to the antifungal agents used. With effective PAP using micafungin, serial serum GM levels showed zero order kinetics during the neutropenic period. CONCLUSION: Although the serum GM assay is a sensitive and specific test for detecting IPA in alloHSCT recipients, its role for routine surveillance in an era of effective PAP with micafungin is limited.
Antifungal Agents ; Fluconazole ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; Invasive Pulmonary Aspergillosis* ; Kinetics ; Mass Screening* ; Retrospective Studies* ; Sensitivity and Specificity ; Seoul ; Stem Cell Transplantation* ; Stem Cells*

PURPOSE: Current clinical data support a safe warm ischemia time (WIT) limit of 30 minutes during laparoscopic partial nephrectomy (LPN) or robot-assisted partial nephrectomy (RPN). We evaluated independent factors predicting prolonged WIT (more than 30 minutes) after LPN or RPN. MATERIALS AND METHODS: A retrospective data review was performed for 317 consecutive patients who underwent LPN or RPN performed by the same surgeon from October 2007 to May 2013. Patients were divided into two groups: group A was defined as prolonged WIT (> or =30 minutes) and group B as short WIT (<30 minutes). We compared clinical factors between the two groups to evaluate predictors of prolonged WIT. RESULTS: Among 317 consecutive patients, 80 were in the prolonged WIT group. Baseline characteristics were not significantly different between the groups. In the univariable analysis, PADUA (preoperative aspects and dimensions used for an anatomical) score (p=0.001), approach method (transperitoneal or retroperitoneal approach; p<0.001), and surgeon experience (p<0.001) were significantly associated with prolonged WIT. In the multivariable analysis, PADUA score (p=0.032), tumor size (> or =25 mm; odds ratio, 2.98; 95% confidence interval, 1.48-5.96; p=0.002), and surgeon experience (p<0.001) were independent predictors of prolonged WIT. CONCLUSIONS: Surgeon experience, tumor size, and PADUA score predicted prolonged WIT after RPN or LPN. Among these factors, increasing surgical experience with LPN or RPN is the most important factor for preventing prolonged WIT.
Adult ; Aged ; Carcinoma, Renal Cell/pathology/*surgery ; Clinical Competence ; Female ; Humans ; Intraoperative Period ; Kidney Neoplasms/pathology/*surgery ; Laparoscopy/methods ; Male ; Middle Aged ; Nephrectomy/*methods ; Pneumoperitoneum, Artificial/*methods ; Retrospective Studies ; Risk Factors ; Robotic Surgical Procedures/methods ; Warm Ischemia/*methods

PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients.
Aged ; Biopsy, Needle/methods ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Precancerous Conditions/*pathology/surgery ; Predictive Value of Tests ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*pathology/surgery ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies

One of the most important prognostic factors in esophageal carcinoma is lymph node metastasis, and in particular, the number of affected lymph nodes, which influences long-term outcomes. The esophageal lymphatic system is connected longitudinally and transversally; thus, the pattern of lymph node metastases is very complex. Early esophageal cancer frequently exhibits skipped metastasis, and minimal surgery using sentinel node navigation cannot be performed. In Korea, most esophageal cancer cases are squamous cell carcinoma (SCC), although the incidence of adenocarcinoma has started to increase recently. Most previous reports have failed to differentiate between SCC and adenocarcinoma, despite the fact that the Union for International Cancer Control (7th edition) and American Joint Committee on Cancer staging systems both consider these separately because they differ in cause, biology, lymph node metastasis, and outcome. Endoscopic tumor resection is an effective and safe treatment for lesions with no associated lymph node metastasis. Esophageal mucosal cancer confined to the lamina propria is an absolute indication for endoscopic resection, and a lesion that has invaded the muscularis mucosae can be cured by local resection if invasion to the lymphatic system has not occurred.
Adenocarcinoma ; Biology ; Carcinoma, Squamous Cell ; Esophageal Neoplasms ; Incidence ; Joints ; Korea ; Lymph Nodes* ; Lymphatic System ; Mucous Membrane ; Neoplasm Metastasis* ; Neoplasm Staging

The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1alpha protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1alpha was increased by 1.69+/-0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1alpha expression by bilirubin. HIF-1alpha expression decreased by 10 microM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1alpha concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1alpha mRNA expression. In coonclusion, bilirubin enhances HIF-1alpha transcription as well as the up-regulation of HIF-1alpha protein translation through the attenuation of ROS and subunits of NADPH oxidase.
Bilirubin/*pharmacology ; Cell Line ; Epithelial Cells/cytology/metabolism ; Humans ; Hydrogen Peroxide/toxicity ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Kidney Tubules, Proximal/cytology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; NADPH Oxidase/antagonists & inhibitors/genetics/metabolism ; Oxygen/*pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism ; Transcriptional Activation/*drug effects ; Up-Regulation/drug effects