Prognostic Value of Erythroblastic Leukemia Viral Oncogene Homolog 2 and Neuregulin 4 in Hepatocellular Carcinoma.

Although the roles of erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuregulin 4 (NRG4), and mitogen-inducible gene 6 (MIG6) in epidermal growth factor receptor signaling in hepatocellular carcinoma (HCC) and other malignancies have been previously investigated, the prognostic value of their serum levels in HCC remains undetermined. In the present study, correlations between serum levels and tumor characteristics, overall survival, and tumor recurrence were analyzed. Furthermore, the prognostic potential of the serum levels of these biomarkers was evaluated relative to that of alpha-fetoprotein. Both ERBB2 and NRG4 correlated with the Barcelona Clinic Liver Cancer stage, ERBB2 correlated with the tumor-maximal diameter, and NRG4 correlated with a tumor number. Cox proportional hazards regression analysis revealed that ERBB2 (hazard ratio [HR], 2.719; p = 0.007) was an independent prognostic factor for overall survival. Furthermore, ERBB2 (HR, 2.338; p = 0.002) and NRG4 (HR, 431.763; p = 0.001) were independent prognostic factors for tumor recurrence. The products of ERBB2 and NRG4 had a better area under the curve than alpha-fetoprotein for predicting 6-month, 1-year, 3-year, and 5-year mortality. Therefore, these factors could be used to evaluate prognosis and monitor treatment response in patients with HCC.

CT-based Hounsfield unit values reflect the degree of steatohepatitis in patients with low-grade fatty liver disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Ultrasound, the most used tool for diagnosing NAFLD, is operator-dependent and shows suboptimal performance in patients with mild steatosis. However, few studies have been conducted on whether alternative noninvasive methods are useful for diagnosing mild hepatic steatosis. Also, little is known about whether noninvasive tests are useful for grading the severity of hepatic steatosis or the degree of intrahepatic inflammation. Therefore, we aimed to evaluate whether the HSI, the FLI and HU values in CT could be used to discriminate mild hepatic steatosis and to evaluate the severity of hepatic steatosis or the degree of intrahepatic inflammation in patients with low-grade fatty liver disease using liver biopsy as a reference standard. METHODS: Demographic, laboratory, CT imaging, and histological data of patients who underwent liver resection or biopsy were analyzed. The performance of the HSI, HU values and the FLI for diagnosing mild hepatic steatosis was evaluated by calculating the area under the receiver operating characteristic curve. Whether the degree of hepatic steatosis and intrahepatic inflammation could be predicted using the HSI, HU values or the FLI was also analyzed. Moreover, we validate the results using magnetic resonance imaging proton density fat fraction as an another reference standard. RESULTS: The AUROC for diagnosing mild hepatic steatosis was 0.810 (p < 0.001) for the HSI, 0.732 (p < 0.001) for liver HU value, 0.802 (p < 0.001) for the difference between liver and spleen HU value (L-S HU value) and 0.813 (p < 0.001) for the FLI. Liver HU and L-S HU values were negatively correlated with the percentage of hepatic steatosis and NAFLD activity score (NAS) and significantly different between steatosis grades and between NAS grades. The L-S HU value was demonstrated the good performance for grading the severity of hepatic steatosis and the degree of intrahepatic inflammation. CONCLUSIONS: The HU values on CT are feasible for stratifying hepatic fat content and evaluating the degree of intrahepatic inflammation, and the HSI and the FLI demonstrated good performance with high sensitivity and specificity in diagnosing mild hepatic steatosis.

Outcomes of laparoscopic radiofrequency ablation versus percutaneous radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: Few studies have compared the therapeutic outcomes in patients with HCC who underwent laparoscopic radiofrequency ablation (LRFA) versus percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC). Therefore, this study compared the recurrence and survival outcomes of the two RFA methods in patients with HCC. METHODS: Recurrence and overall survival outcomes were evaluated in 307 patients who underwent LRFA (n = 151) or PRFA (n = 156) as a treatment method for de novo HCC. Inverse probability of treatment weighting (IPTW) analysis was performed to reduce the impact of treatment selection bias. RESULTS: There were no significant differences in major baseline characteristics between the LRFA and PRFA groups. However, the proportion of cirrhotic patients was higher in the LRFA group, whereas the LRFA group had more tumors and a more advanced tumor-node-metastasis stage. Moreover, the mean tumor size was significantly larger in the LRFA group than in the PRFA group. In a multivariate analysis, serum albumin level, more than three tumors, and the RFA method were identified as significant predictors of recurrence-free survival. Moreover, for the overall survival of HCC patients, serum albumin levels, days of hospital stay during RFA, and the RFA method were independent predictors. In the IPTW-adjusted analysis, the LRFA group showed significantly higher recurrence-free survival and overall survival. CONCLUSIONS: Our study revealed that compared with PRFA, LRFA was associated with longer recurrence-free survival and favorable overall survival in patients with HCC. Therefore, LRFA should be considered the primary therapy in patients with HCC eligible for RFA.

Status of Using Complementary and Alternative Medicine among Patients with Cancer in Korea: an Online Survey of Online Cancer Support Groups (KCSG PC21-20).

PURPOSE: An increasing number of patients with cancers are interested in complementary and alternative medicine (CAM), which lacks scientific evidence. This study aimed to determine how CAM was used and how media affected patients in online cancer support groups (OCSG). Materials and Methods: Between August 18 and September 12, 2021, an online survey was conducted among the members of OCSG. The survey consisted of five parts: baseline characteristics, attitudes toward and experience with CAM, source of information and reliabilities, experience with anthelmintics, and online health information literacy and usage. RESULTS: Among the 644 responders, a total of 221 patients with cancer completed the survey, and 78.2% (173/221) used CAM. The users' median age was 52 years; 46.8% were males, and 43.9% had metastatic disease. Fifty-three CAM users (30.6%) discussed their physicians about CAM. In addition, 16.2% (28/173) of CAM users had the experience of anthelmintics. The use of anthelmintics in patients with cancers was associated with younger age (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84 to 0.95), metastatic disease (OR, 10.88; 95% CI, 3.39 to 34.86), previous exposure to CAM information (OR, 5.57; 95% CI, 1.01 to 30.72), experience with more types of CAM (OR, 1.98; 95% CI, 1.29 to 3.05), and side effects (OR, 5.10; 95% CI 1.46 to 17.75). CONCLUSION: Use of anthelmintics, a CAM of which information is widespread online, is affected by several factors. This study will provide essential information for developing a CAM management strategy in this digital age.

The Tri-iodothyronine (T3) Level Is a Prognostic Factor for Patients With Advanced NSCLC: Receiving Immune Checkpoint Inhibitors and Is Associated With Liver Metastasis.

Background: Endocrine hormones influence tumor progression and the response to treatment. Despite the importance of immune checkpoint inhibitors (ICIs) as treatments for advanced non-small cell lung cancer (NSCLC), few studies have explored the effects of hormone levels in NSCLC patients on the effectiveness of ICI therapies. We thus investigated the effects of baseline blood markers in patients with advanced NSCLC on ICI treatments. Methods: Patients with advanced NSCLC who received programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors at Chungnam National University Hospital between December 2016 and November 2020 and who lacked any history of thyroid gland-related diseases were analyzed retrospectively. We collected clinical information and baseline laboratory data, including the levels of endocrine hormones, cytokines, complete blood counts (CBCs), and peripheral blood chemistry panels. We explored the relationships of hormone levels with clinical outcomes (overall survival [OS], progression-free survival [PFS], and best response), liver metastasis, and blood markers using the Kaplan-Meier method, Cox's proportional hazards regression, and logistic regression. Results: A total of 113 patients were enrolled. A shorter PFS was independently associated with liver metastasis, higher cortisol levels, and lower hemoglobin (Hb) levels; a shorter OS was associated with liver metastasis, lower tri-iodothyronine (T3) levels, higher lactate dehydrogenase (LDH) levels, and lower albumin levels. Patients with low T3 levels exhibited a shorter PFS and OS, and a poorer best response. Patients with low T3 levels tended to have higher disease progression rates, lower levels of adrenocorticotropic hormone (ACTH), C-peptide, albumin, Hb, and neutrophil-to-lymphocyte ratio, and higher levels of interleukin (IL)-6, white blood cells, platelets, compared with those with normal T3 levels. We found a significant association between a low T3 level and liver metastasis. Conclusions: We found the baseline T3 level was associated with both prognosis and the response to ICIs in patients with advanced NSCLC, probably reflecting impaired liver function and systemic inflammation induced by the interaction of T3 with other biomarkers, such as IL-6, ACTH, cortisol, C-peptide, Hb, LDH, and albumin.

Validation and modification of existing mortality prediction models for lower gastrointestinal bleeding: a retrospective study.

BACKGROUND: Lower gastrointestinal bleeding (LGIB) often subsides without medical intervention; however, in some cases, the bleeding does not stop and the patient's condition worsens. Therefore, predicting severe LGIB in advance can aid treatment. This study aimed to evaluate variables related to mortality from LGIB and propose a scoring system. METHODS: In this retrospective study, we reviewed the medical records of patients who visited the emergency room with hematochezia between January 2016 and December 2020. Through regression analysis of comorbidities, medications, vital signs, laboratory investigations, and duration of hospital stay, variables related to LGIB-related mortality were evaluated. A scoring system was developed and the appropriateness with an area under the receiver operating characteristics curve (AUROC) was evaluated and compared with other existing models. RESULTS: A total of 932 patients were hospitalized for LGIB. Variables associated with LGIB-related mortality were the presence of cancer, heart rate > 100 beats/min, blood urea nitrogen level ≥ 30 mg/dL, an international normalized ratio > 1.50, and albumin level ≤ 3.0 g/dL. The AUROCs of the models CNUH-4 and CNUH-5 were 0.890 (p < 0.001; cutoff, 2.5; 95% confidence interval, 0.0851-0.929) and 0.901 (p < 0.001; cutoff, 3.5; 95% confidence interval, 0.869-0.933), respectively. CONCLUSIONS: The model developed for predicting the risk of LGIB-related mortality is simple and easy to apply clinically. The AUROC of the model was better than that of the existing models.

Predictor of Subungual Melanoma against Benign Longitudinal Melanonychia: A Retrospective Cohort Study from Korea.

BACKGROUND: Longitudinal melanonychia (LM) is a common clinical finding. Most cases of LM are benign, and a wait-and-see approach is preferred in the management of this condition. Nevertheless, it is important for clinicians to distinguish subungual melanoma (SUM) from other benign LMs. OBJECTIVE: To evaluate the demographic and clinicopathologic characteristics of LM in the Korean population and to identify the predictor of SUM against other benign conditions. METHODS: This was a single-center retrospective cohort study including patients who underwent nail biopsy for LM from January 2000 to May 2019. To identify the predictor of SUM, receiver operating characteristic (ROC) analyses was performed. RESULTS: A total of 68 cases of biopsy-proven LM were included in the analysis. Among the 68 cases, 8 were SUM. In univariable analysis, patients diagnosed with SUM were older (p=0.035) and had a longer disease duration (p=0.004). They also showed multicolor pigmentation of LM (p=0.022), a larger width of LM (p<0.001), and associated nail plate dystrophy (p=0.010) than patients diagnosed with benign conditions. In multivariable logistic regression, width of LM showed statistical significance (odds ratio, 1.083; 95% confidence interval, 1.018~1.153). ROC analysis suggested that an LM width >28% of the whole nail was the predictor of SUM (area under the curve=0.883; p<0.001). CONCLUSION: SUM has distinct demographic and clinical features. The width of LM can predict SUM against other benign LMs.

Which scoring system should be used for non-variceal upper gastrointestinal bleeding? Old or new?

BACKGROUND AND AIM: Several scoring systems for predicting outcomes in patients with non-variceal upper gastrointestinal bleeding (NVUGIB) have recently been devised, but not sufficiently validated. We compared the predictive accuracy of several scoring systems and assessed the usefulness of new scoring systems. METHODS: The medical records of 1048 patients with NVUGIB were reviewed to collect demographic, clinical, laboratory, and endoscopic data. The areas under the receiver operating characteristic curve (AUROCs) were calculated for the ABC, new Japanese scoring system, Progetto Nazionale Emorrhagia Digestiva (PNED), and other scores to compare their predictive accuracy for 30-day mortality, therapeutic intervention, rebleeding, and prolonged hospital stay (≥ 10 days). Outcome predictors were identified by multivariate analysis. RESULTS: The ABC, new Japanese scoring system, and PNED scores best predicted 30-day mortality (AUROC 0.907), need for therapeutic intervention (AUROC 0.707), and rebleeding (AUROC 0.874), respectively (all P < 0.001). The ABC and PNED scores were similarly better at predicting prolonged hospital stay (ABC AUROC: 0.765; PNED AUROC: 0.790; both P < 0.001). Thirty-day mortality was related to sex, systolic blood pressure (SBP), syncope, estimated glomerular filtration rate (eGFR), albumin, heart failure, disseminated malignancy, chronic obstructive pulmonary disease (COPD), and liver cirrhosis. Sex, age, SBP, hematemesis, blood urea nitrogen, and eGFR independently predicted the need for therapeutic intervention. Sex, SBP, pulse, albumin level, heart failure, disseminated malignancy, and COPD predicted rebleeding. CONCLUSION: The outcomes of patients with NVUGIB were better predicted by newly developed than by old scoring systems.

Pharmacokinetic equivalence of CT-P17 to high-concentration (100 mg/ml) reference adalimumab: A randomized phase I study in healthy subjects.

This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT-P17 to United States-licensed adalimumab (US-adalimumab) and European Union-approved adalimumab (EU-adalimumab). This double-blind, parallel-group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT-P17, US-adalimumab, or EU-adalimumab. Primary end points were PK equivalence in terms of: area under the concentration-time curve from time zero to infinity (AUC0-inf ); AUC from time zero to the last quantifiable concentration (AUC0-last ); and maximum serum concentration (Cmax ). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80-125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT-P17; 103 US-adalimumab; 106 EU-adalimumab), 308 subjects received study drug. AUC0-inf , AUC0-last , and Cmax were equivalent among CT-P17, US-adalimumab, and EU-adalimumab, because 90% CIs for the ratios of GLSMs were within the 80-125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single-dose administration of CT-P17, EU-adalimumab, and US-adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars.

Development and Validation of a Risk Scoring Model for Early Prediction of Severe Colon Ischemia.

BACKGROUND: Colon ischemia (CI) is injury to the intestines secondary to insufficient blood flow. Its clinical severity can range from mild to life-threatening. AIMS: To investigate predictive risk factors for CI and propose a scoring model for severe outcomes. METHODS: We retrospectively analyzed the medical records of patients admitted to Chungnam National University Hospital from January 2010 to December 2018. CI was defined as severe when patients required surgery immediately or after initial conservative management, death occurred after hospitalization, or symptoms persisted after 2 weeks. By controlling for possible confounders from the logistic regression analysis, we obtained a new risk scoring model for the early prediction of severe CI. Furthermore, using the area under the receiver operating characteristics curve (AUROC), we assessed the accuracy of the model. RESULTS: A total of 274 patients endoscopically diagnosed with CI were included, of whom 181 had severe CI. In the multivariate analysis, tachycardia, elevated C-reactive protein, Favier endoscopic classification stage ≥ 2, and history of hypertension were independently and significantly associated with severe CI. The AUROC of the model was 0.749. CONCLUSIONS: This risk scoring model based on the presence of tachycardia, elevated C-reactive protein level, unfavorable endoscopic findings by Favier's classification, and the history of hypertension could be used to predict severe CI outcomes at an early stage.

Comparison of conventional and modified endoscopic mucosal resection methods for the treatment of rectal neuroendocrine tumors.

BACKGROUND/AIM: Small rectal neuroendocrine tumors (NETs) confined to the submucosa are endoscopically resectable. Because most rectal NETs are submucosal tumors, conventional endoscopic mucosal resection (cEMR) may not result in a complete resection. This study investigated whether modified EMRs, namely endoscopic submucosal resection with ligation (ESMR-L), EMR with precutting (EMR-P), and strip biopsy are superior to cEMR for achieving histologically complete resection (HCR) of rectal NETs. METHODS: Medical records of 215 patients who were treated with endoscopic resections for rectal NETs between January 2011 and July 2019 were retrospectively enrolled. Of the patients, 110, 33, 29, and 43 underwent cEMR, ESMR-L, EMR-P, and strip biopsy, respectively. For each method, HCR and en bloc resection rates, procedure times, and complication rates were measured. RESULTS: HCR was achieved with cEMR, EMR-P, ESMR-L, and strip biopsies for 74.5%, 90.9%, 93.1%, and 90.7% of cases, respectively. The HCR rate for cEMR was inferior to those of the modified EMRs (p = 0.045 for cEMR vs. EMR-P; p = 0.031 for cEMR vs. ESMR-L; p = 0.027 for cEMR vs. strip biopsy). Among the three modified EMRs, there was no significant difference in achieving HCR (p = 1.000). En bloc resection (p = 0.096) and complication rates (p = 0.071) were not significantly different among the four EMR methods, although EMR-P required the longest procedure time (p = 0.000). CONCLUSIONS: All three modified EMRs are superior to cEMR and are equally effective for achieving HCR of rectal NETs.

Self-expandable metal stent of esophagogastric junction versus pyloric area obstruction in advanced gastric cancer patients: Retrospective, comparative, single-center study.

Upper gastrointestinal stenting is a palliative treatment for relieving symptoms such as nausea, vomiting, and dietary intake in patients with obstruction due to inoperable advanced stomach cancer. Self-expandable metal stent (SEMS) implantation for malignant obstruction has recently become more effective, safer, and less expensive than operative modality. It also has better short-term outcomes, particularly a shorter hospital stay and a more rapid return to oral intake, than surgical treatment. However, there is no comparative analysis regarding the efficacy, side effects, and survival rate of stenting between the esophagogastric junction (EGJ) and pyloric obstructions.To compare the prognoses and complications after SEMS implantation between EGJ and pyloric obstructions in advanced gastric cancer.Among advanced gastric cancer patients with gastrointestinal obstruction diagnosed from January 2008 to December 2017 at the Gastroenterology Department of Chungnam National University Hospital, 42 and 76 patients presented with EGJ (EGJ obstruction group) and gastric pyloric obstructions (pyloric obstruction group), respectively. We retrospectively reviewed the survival period, changes in food intake, and complications of these patients before and after SEMS placement.The prevalences of aspiration pneumonia were 11.9% (5/42) and 2.6% (2/76) in the EGJ and pyloric obstruction groups, respectively, before SEMS placement (P value: .041). Other symptoms associated with gastric malignant obstruction were not statistically different between the groups. Success rate and adverse events did not significantly differ between the EGJ and pyloric obstruction groups. There was no difference in frequency of stent reinsertion procedures performed owing to reobstruction, but the reprocedure average period was statistically significantly longer in the EGJ obstruction group [EGJ obstruction: 158.3 days (±42.4); pyloric obstruction: 86.0 days (±29.1)] (P value: .022). As an index of improved dietary status, the Gastric Outlet Obstruction Scoring System score was not significantly different between the groups before and after SEMS placement.The EGJ and pyloric obstruction groups did not significantly differ in prognosis or complication rates. However, EGJ stent was more stable than pyloric stent when reobstruction was considered.

Pharmacokinetic comparison of two bazedoxifene acetate 20 mg tablet formulations in healthy Korean male volunteers.

Bazedoxifene, used as bazedoxifene acetate, is a selective estrogen receptor modulator that selectively affects the uterus, breast tissue, bone metabolism, and lipid metabolism by antagonizing or enhancing estrogens in the estrogen receptor in the tissue. This study was conducted as an open, randomized, two-period, two-treatment, crossover design to compare the pharmacokinetic (PK) characteristics and tolerability of two bazedoxifene tablets when administered to 50 healthy Korean male volunteers. Enrolled subjects were randomly allocated to 2 sequences of a single oral administration of a test drug and a reference drug, or vice versa with a 14-day washout period between the two doses. Serial blood samples were collected over 96 h for PK analysis. Plasma concentration of bazedoxifene was assayed using liquid chromatography-tandem spectrometry mass. Forty-five participants completed the study with no clinically relevant safety issues. The peak concentrations (Cmax, mean ± strandard deviation) of reference drug and test drug were 3.191 ± 1.080 and 3.231 ± 1.346 ng/mL, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) were 44.697 ± 21.168 ng∙h/mL and 45.902 ± 23.130 ng∙h/mL, respectively. The geometric mean ratios of test drug to reference drug and their 90% confidence intervals for Cmax and AUClast were 0.9913 (0.8828-1.1132) and 1.0106 (0.9345-1.0929), respectively. The incidence of adverse events between the two formulations was similar. The present study showed that PK and tolerability of two bazedoxifene tablet formulations were comparable when administered to healthy Korean male volunteers. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003978.

The incidence and risk factors of sessile serrated adenomas in left side colon cancer patients after curative surgery.

Sessile serrated adenomas (SSAs) are precursors of colorectal cancer (CRC). However, there are limited data on detection rates of this premalignant lesion during colonoscopy surveillance in patients with a history of left side colonic resection for cancer. We aimed to identify the incidence and risk factors of SSAs in post-left side colectomy patients.We retrospectively reviewed the medical records of patients who had undergone left side colectomy for colon and rectal cancer between September 2009 and September 2016 and had at least 1 follow-up colonoscopy. Patient baseline characteristics, SSA diagnoses and characteristics, and colonoscopy information were collected.In total, 539 patients were enrolled. At the first follow-up (mean duration 11.5 months), 98 SSAs were identified (22.2%). At the second follow-up (mean duration 25.8 months), 51 SSAs were identified in 212 patients (24.0%). Multivariate analysis showed that alcohol intake (hazard ratio [HR] 1.524; 95% confidence interval [CI] .963-2.411, P = .041), excellent bowel preparation (HR 2.081; 95% CI 1.214-3.567, P = .049), and use of a transparent cap (HR 1.702; 95% CI 1.060-2.735, P = .013) were associated with higher SSA incidence in the first surveillance colonoscopy, while body mass index (BMI) ≥ 25.0 (HR 1.602; 95% CI 1.060-2.836) was associated with a significantly increased risk of SSAs in the second surveillance.Considering the endoscopic appearance of SSAs, adequate bowel preparation and use of transparent caps during postoperative surveillance colonoscopy can increase the diagnosis rate. Modification of alcohol intake and BMI may reduce the incidence of SSAs in left side colon cancer patients.

Identification of a Clinical Cutoff Value for Multiplex KRASG12/G13 Mutation Detection in Colorectal Adenocarcinoma Patients Using Digital Droplet PCR, and Comparison with Sanger Sequencing and PNA Clamping Assay.

KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) is a major predictive marker for anti-epidermal growth factor receptor treatment, and determination of KRAS mutational status is crucial for successful management of colorectal adenocarcinoma. More standardized and accurate methods for testing KRAS mutation, which is vital for therapeutic decision-making, are required. Digital droplet polymerase chain reaction (ddPCR) is an advanced digital PCR technology developed to provide absolute quantitation of target DNA. In this study, we validated the clinical performance of ddPCR in determination of KRAS mutational status, and compared ddPCR results with those obtained by Sanger sequencing and peptide nucleic acid-clamping. Of 81 colorectal adenocarcinoma tissue samples, three repeated sets of KRASG12/G13 mutation were measured by ddPCR, yielding high consistency (ICC = 0.956). Receiver operating characteristic (ROC) curves were constructed to determine KRASG12/G13 mutational status based on mutant allele frequency generated by ddPCR. Using the best threshold cutoff (mutant allele frequency of 7.9%), ddPCR had superior diagnostic sensitivity (100%) and specificity (100%) relative to the two other techniques. Thus, ddPCR is effective for detecting the KRASG12/G13 mutation in colorectal adenocarcinoma tissue samples. By allowing definition of the optimal cutoff, ddPCR represents a potentially useful diagnostic tool that could improve diagnostic sensitivity and specificity.

Analysis of factors associated with local recurrence after endoscopic resection of gastric epithelial dysplasia: a retrospective study.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely used techniques for the treatment of gastric epithelial dysplasia. Previous studies have compared the clinical outcome of endoscopic resection for early gastric cancer, but few studies have focused on gastric dysplasia alone. This study aimed to evaluate the long-term prognosis following endoscopic procedures for gastric epithelial dysplasia, investigate differences in local recurrence rates according to the treatment modality, and identify risk factors associated with local recurrence. METHODS: In this retrospective study, local recurrence rates and risk factors associated with local recurrence were compared between 599 patients who underwent EMR and 306 who underwent ESD for gastric epithelial dysplasia from January 2011 to December 2015. RESULTS: The en bloc resection rate (32.2% vs. 100%, p < 0.001) and complete resection rate (94.8% vs. 99.0%, p = 0.003) were significantly lower in the EMR group than in the ESD group. The local recurrence rate was significantly lower in the ESD group (1.3%) than in the EMR group (4.2%; p = 0.026). There was a significantly increased risk of local recurrence, regardless of lesion location or histologic grade, in patients with lesions > 2 cm (p = 0.002) or red in color (p = 0.03). The ESD group had a significantly lower local recurrence rate, with a higher complete resection rate, than that in the EMR group (p < 0.05). In the case of recurrence after endoscopic resection, most of the recurred lesions were removed through additional endoscopic procedures; there was no difference between the two groups (p = 0.153). CONCLUSIONS: The complete resection rate was significantly higher, and the local recurrence rate was significantly lower, in patients with gastric epithelial dysplasia treated with ESD. Therefore, ESD should be considered the preferred treatment in patients with lesions > 2 cm or showing redness due to an increased risk of local recurrence and EMR may be possible for low-grade dysplasia that is less than 2 cm without surface changes such as redness, depression and nodularity.

TEAD2 as a novel prognostic factor for hepatocellular carcinoma.

TEA Domain Transcription Factors (TEADs) are important in development and serve essential roles in tumorigenesis; however, the role of TEAD2 expression in hepatocellular carcinoma (HCC) has not been widely examined. The present study was conducted to investigate the expression status of TEAD2 in HCC and to evaluate whether the expression of TEAD2 is associated with the prognosis of patients with HCC. mRNA expression data was retrieved for Hippo pathway genes of 50 normal control and 377 HCC samples from The Cancer Genome Atlas data portal. Gene set enrichment, GeneNeighbors, ClassNeighbors and survival analyses were then performed based on the gene expression levels. The mRNA expression of TEAD2 and VGLL4 was significantly higher in HCC compared with the normal control samples, and the mRNA expression of TEAD2 was higher in advanced stages than in early stages. Specifically, survival analysis revealed that higher mRNA expression of TEAD2 was significantly associated with a less favorable overall survival rate (P=0.0067) and there was a trend towards significance between higher mRNA expression of VGLL4 and poor overall survival rate (P=0.051). According to the gene set enrichment analysis, patients with higher mRNA expression of TEAD2 and VGLL4 had strongly enhanced epithelial­mesenchymal transition and angiogenesis, which are associated with tumor progression. In conclusion, increased mRNA expression of TEAD2 is associated with a poor prognosis in patients with HCC. TEAD2 may serve as a prognostic factor for HCC and a novel therapeutic target.

Quality of Preoperative Colonoscopy Affects Missed Postoperative Adenoma Detection in Colorectal Cancer Patients.

BACKGROUND: Despite thorough preoperative screening, 19-30% of synchronous polyps or adenomas are detected after colon cancer surgery. Remnant synchronous lesions require additional colonoscopy procedures or surgery. AIM: To investigate factors of preoperative colonoscopy potentially affecting the detection of missed lesions in patients subjected to colorectal cancer surgery. METHODS: Of 1147 colorectal cancer patients subjected to curative open or laparoscopic colectomy and colonoscopy at the Chungnam National University Hospital from January 2012 to December 2016, 518 patients underwent pre- and postoperative colonoscopy. The index colonoscopy was defined as the last preoperative endoscopy performed. We analyzed pre- and postoperative medical charts for colonoscopy and pathological data. The effects of patient, procedure, and tumor factors on the postoperative adenoma detection rate, advanced adenoma detection rate, and adenoma miss rate (AMR) were analyzed. RESULTS: The overall AMR was 25.7% (95% confidence interval, 22.2-29.8%). Comparing optimal and non-optimal bowel preparation groups, the latter had greater postoperative polyp missed rate (PMR), AMR (p < 0.01), and AAMR (p = 0.272). The optimal preparation group allowed identification of more synchronous adenomas than in the fair (OR 5.72) and poor (OR 11.39) preparation groups. On univariate analysis, patient age and left-sided colectomy (p < 0.01) influenced AMR. Multivariate analysis showed that age, preoperative bowel preparation, and left colon resection influenced postoperative AMR. CONCLUSION: A better quality of index colonoscopy had a positive effect on lowering the detection rate of postoperative adenoma. Older age and suboptimal bowel preparation at the index colonoscopy and left-sided colectomy had negative effects on lowering the postoperative AMR.

Prognostic Significance of LC3B and p62/SQSTM1 Expression in Gastric Adenocarcinoma.

BACKGROUND/AIM: Autophagy is a cellular mechanism that recycles cellular components to maintain homeostasis. To investigate the clinical implication of autophagy in gastric cancer, the autophagy markers with autophagosome formation, LC3B and selective autophagy substrate p62/SQSTM1 (P62) were validated. MATERIALS AND METHODS: LC3B and p62 expression was examined using immunohistochemistry, western blot assays, and reverse-transcription polymerase chain reaction (RT-PCR). The relationship of LC3B and p62 expression in gastric adenocarcinomas with clinicopathological parameters, including patient survival, were analyzed. RESULTS: Normal gastric mucosae exhibit no LC3B and p62 expression, while tubular adenoma and gastric adenocarcinomas exhibit variable nuclear or cytoplasmic p62 expression. High LC3B, high cytoplasmic p62, and low nuclear p62 protein expression in gastric adenocarcinomas is positively correlated with poor prognostic factors including survival. CONCLUSION: Dynamic LC3B and p62 changes are suggested to be involved in gastric tumorigenesis and cancer progression. LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for gastric adenocarcinomas.

Role of preoperative endoscopic clipping in laparoscopic distal gastrectomy for early gastric cancer.

In this study, we evaluate the usefulness of preoperative endoscopic clipping for early gastric cancer (EGC) localization in laparoscopic distal gastrectomy.We retrospectively screened all consecutive patients who underwent laparoscopic distal gastrectomy for EGC by 1 surgeon at Chungnam National University Hospital between January 2014 and December 2016. Patients who underwent combined surgery and patients who had tumors at the lower third of the stomach were excluded. Endoscopic clipping was performed prior to surgery by specialized endoscopists. During the operation, endoscopic metal clips were found using surgical devices, and laparoscopic vessel clips were attached on the presumed site; thereafter, intraoperative radiographs were obtained for confirmation.We analyzed a total of 196 patients; of them, 101 were classified into the clipping group (CG) and 95 into the non clipping group (NCG). The 2 groups were comparable regarding their demographic characteristics. The CG showed less additional resection (2 of 101 patients [2.0%] vs 9 of 95 patients [9.4%], P = .021) and better outcomes in terms of the operation time (P = .000), duration of hospital stay (P = .036), and postoperative atelectasis (P = .001) than the NCG.Preoperative endoscopic clipping was helpful in determining the exact resection margin in laparoscopic distal gastrectomy for EGC.