Comparison of cytological and histological preparations in the diagnosis of pancreatic malignancies using endoscopic ultrasound-guided fine needle aspiration.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has become a crucial diagnostic technique for pancreatic malignancies. The specimen obtained by EUS-FNA can be prepared for either cytological or histological examinations. This study was to compare diagnostic performance of cytological and histological preparations using EUS-FNA in the same lesions when pancreatic malignancies were suspected. METHODS: One hundred and eighteen patients who underwent EUS-FNA for suspected pancreatic malignancies were consecutively enrolled. All procedures were conducted by a single echoendoscopist under the same conditions. Four adequate preparations were obtained by 22-gauge needles with 20 to-and-fro movements for each pass. The 4 preparations included 2 cytological and 2 histological specimens. The pathologic reviews of all specimens were conducted independently by a single experienced cytopathologist. Sensitivity, specificity, and accuracy of the 2 preparations were compared. RESULTS: The enrolled patients consisted of 62 males (52.5%), with the mean age of 64.6±10.5 years. Surgery was performed in 23 (19.5%) patients. One hundred and sixteen (98.3%) lesions were classified as malignant, while 2 (1.7%) were benign. Sensitivity of cytology and histology were 87.9% and 81.9%, respectively, with no significant difference (P=0.190). Accuracy was also not significantly different. Cytological preparation was more sensitive when the size of lesion was <3 cm (86.7% vs 68.9%, P=0.033). CONCLUSIONS: Our results suggested that the diagnostic performances of cytological and histological preparations are not significantly different for the diagnosis of pancreatic malignancies. However, cytological preparation might be more sensitive for pancreatic lesions <3 cm.

Neutrophil-lymphocyte ratio predicts survival in patients with advanced cholangiocarcinoma on chemotherapy.

The blood neutrophil-to-lymphocyte ratio (NLR) is reported to be a prognostic marker in several cancers. However, the prognostic role of NLR in patients with advanced cholangiocarcinoma on chemotherapy is unknown. A total of 221 patients with pathologically confirmed locally advanced or metastatic cholangiocarcinoma receiving first-line palliative chemotherapy were enrolled. Associations between baseline clinical and laboratory variables including NLR and survival were investigated. Patients were classified into two groups according to the NLR level (≤ 5 vs. >5). Median overall survival (OS) and time to progression (TTP) in patients with NLR ≤ 5 were 10.9 and 6.7 months, respectively, and 6.8 and 4.1 months in patients with NLR > 5 (P < 0.001, P = 0.002, respectively). In multivariate analysis, number of cycles of chemotherapy was a significant predictor of longer OS (HR 0.86, P < 0.001), whereas adverse prognostic factors for OS were CA 19-9 > 300 (HR 1.43, P = 0.025), CEA > 5 (HR 1.44, P = 0.029), higher stage (HR 1.69, P = 0.004), and NLR > 5 (HR 1.87, P < 0.001). NLR > 5 was also associated with reduced TTP (HR 1.66, P = 0.007). Among 50 patients with initial NLR > 5, 33 patients had NLR ≤ 5 after two cycles of chemotherapy and they had significantly better survival than the others (HR 0.48, P = 0.015). NLR independently predicts survival in patients with advanced cholangiocarcinoma undergoing chemotherapy. Considering cost-effectiveness and easy availability, NLR may be a useful biomarker for prognosis prediction.

Total Colonic Decompression After Colonoscopy Decreases Postcolonoscopy Abdominal Pain: A Randomized Double-Blind Controlled Trial.

GOALS: The purpose of this study was to determine whether total colonic decompression after colonoscopy decreased postcolonoscopy abdominal pain. BACKGROUND: Abdominal pain that occurs after a colonoscopy may cause significant discomfort in some patients, and residual bowel gas is thought to be a key contributor to this abdominal pain. STUDY: Asymptomatic 300 patients who underwent colonoscopy under sedation were randomized to either the decompression group or the control group. Initial colonoscopic procedure was performed uniformly in both the groups. After the colonoscopy examination was completed, the colonoscope was reinserted into the cecum, and the intraluminal air was aspirated during withdrawal in the decompression group. Abdominal pain was assessed before discharge and 24 to 48 hours after colonoscopy using a 10-point visual analogue scale (VAS). RESULTS: The 2 groups were similar with regard to clinical, demographic, and procedural factors. Among 288 patients, the incidence of abdominal pain (VAS≥1) after colonoscopy was 38 (26.6%) of 143 patients in the decompression group and 95 (65.5%) of 145 patients in the control group (VAS 0.68±1.35 vs. 2.14±2.15, P<0.001). There was an 86.1% reduction rate of abdominal pain by colonic decompression, based on multivariate analysis (odds ratio 0.139 [95% confidence interval, 0.077-0.250], P<0.001). Furthermore, independent factors for abdominal pain included female gender and total duration of procedure >800 seconds. There were no reinsertion-related complications in the decompression group. CONCLUSION: Total colonic decompression after colonoscopy has a beneficial effect and can reduce postcolonoscopy abdominal pain without additional complications.

Early decrement of serum carbohydrate antigen 19-9 predicts favorable outcome in advanced pancreatic cancer.

BACKGROUND AND AIM: The role of carbohydrate antigen 19-9 (CA 19-9) for predicting treatment outcome in pancreatic ductal adenocarcinoma (PDAC) remains to be elucidated. This study was aimed to determine the correlation between early decrement in CA 19-9 concentration and prognosis of advanced PDAC after chemotherapy. METHODS: All patients confirmed with locally advanced or metastatic PDAC who received initial systemic chemotherapy for at least two cycles in our institution between January 2012 and December 2013 were included. Serum CA 19-9 concentrations at baseline and 8 weeks after the initiation of chemotherapy were obtained. Correlation between CA 19-9 decrement and survival outcomes (time to progression [TTP] and overall survival [OS]) were evaluated. RESULTS: A total of 183 patients with initially elevated CA 19-9 were included. OS and TTP was significantly longer for patients whose serum CA 19-9 concentration decreased more than 10% from baseline (n = 103), than that for patients whose serum CA 19-9 was not decreased (n = 80) (423 vs 155 days, P < 0.001 for OS and 222 vs 75 days, P < 0.001 for TTP). In multivariate analysis, CA 19-9 decrement more than 10% from baseline was still a significant factor for longer OS (hazard ratio for progression 0.275 [0.184-0.412], P < 0.001) and TTP (0.322 [0.219-0.473], P < 0.001) in both stage III and IV. CONCLUSIONS: The early decrement of CA 19-9 after the initiation of chemotherapy was an independent factor related with better survival outcomes in unresectable PDAC.

Prognostic value of CA 19-9 kinetics during gemcitabine-based chemotherapy in patients with advanced cholangiocarcinoma.

BACKGROUND: Little is known of the prognostic value of CEA/CA 19-9 kinetics during chemotherapy in patients with advanced cholangiocarcinoma (CCA). METHODS: A total of 236 patients with pathologically confirmed advanced CCA received gemcitabine-based chemotherapy were reviewed, and 179 were eligible for analysis. Baseline, pre-, and post-treatment (after two cycles of chemotherapy) CEA and CA 19-9 values were checked, and survival was compared according to various cutting points of baseline measurement or extent of change of tumor marker level. RESULTS: Patients with a ≥ 50% decline in CA 19-9 level had better survival than the others (16.0 vs 9.0 months). However, CEA decline did not predict survival gain. Significant favorable prognostic factors of survival in multivariable analysis included initial treatment response (HR 0.61), distal location of tumor (HR 0.46), baseline CA 19-9 level ≤ 1000 U/mL (HR 0.58), and ≥ 50% decline in CA 19-9 level (HR 0.50). Subgroup analysis was conducted in 114 patients with pre-treatment CA 19-9 > 37 U/mL and bilirubin ≤ 2 mg/dL. Decline ≥ 50% in CA 19-9 level still showed an independent prognostic significance (HR 0.45). CONCLUSION: CA 19-9 but not CEA kinetics serves as a predictor of better survival in patients with advanced CCA on gemcitabine-based chemotherapy. A ≥ 50% decline in CA 19-9 level after two cycles of chemotherapy may have clinical utility as an early indicator of better response to gemcitabine-based chemotherapy.

Reintervention for occluded metal stent in malignant bile duct obstruction: A prospective randomized trial comparing covered and uncovered metal stent.

BACKGROUND AND AIM: No prospective data are available on comparing covered and uncovered self-expandable metal stent (SEMS) for reintervention of occluded uncovered metal stents during endoscopic retrograde cholangiopancreatography in patients with malignant distal biliary obstruction. METHODS: From June 2010 to November 2014, 43 patients with inoperable distal biliary obstruction of a previously placed uncovered SEMS were enrolled from three centers in Korea and randomly assigned to covered (n = 22) or uncovered SEMS group (n = 21). The primary outcome was overall stent patency. Secondary outcome was time-to-stent occlusion, patient survival, cause of stent occlusion, and adverse events. RESULTS: Overall median patency of secondary stent was 112.0 days. Median stent patency of covered and uncovered SEMS was 112.0 and 181.0 days, respectively, (P = 0.373). There was a tendency towards a longer time-to-stent occlusion in uncovered SEMS group (median: 112.0 vs 181.0 days). However, it did not reach statistical significance (P = 0.214). Most common causes of occlusion were stent clogging (36.4%) and tumor ingrowth (33.3%) in covered and uncovered SEMS groups, respectively. There was no significant difference in median survival between the groups (median: 308 vs 300 days; P = 0.325). Acute cholangitis occurred in four patients (three in covered vs one in uncovered SEMS group, P = 0.607). CONCLUSIONS: In this exploratory trial, there were no statistically significant differences in stent patency, time-to-stent occlusion, patient survival, and complication rates between covered and uncovered SEMS groups. Larger confirmatory multicenter trial is needed for the clear conclusion (ClinicalTrials.gov: NCT01315522).

Risk factors for perihilar cholangiocarcinoma: a hospital-based case-control study.

BACKGROUND & AIMS: Perihilar cholangiocarcinoma (pCCA) is the most common form of bile duct cancer, arising from cholangiocytes at the confluence of hepatic ducts. Given the diversity of cholangiocarcinoma (CCA) aetiology according to the location, and the scarcity of studies on the aetiology of pCCA, we aimed to identify the risk factors for pCCA. METHODS: A total of 81 patients diagnosed with pCCA between July 2007 and December 2013, and 162 controls matched 2:1 for age, sex and date of diagnosis were included in this hospital-based case-control study. Potential risk factors were retrospectively investigated through clinical records, and the associations with pCCA were studied by calculating the odds ratios (ORs) using conditional logistic regression analysis. RESULTS: In the univariate model, the prevalence of choledocholithiasis (OR: 14.00, P = 0.014), hepatolithiasis (OR: 12.00, P = 0.021) and diabetes mellitus (DM) (OR: 2.74, P = 0.005) was higher in pCCA patients than in controls. Heavy smoking and cirrhosis were marginally significant risk factors for pCCA (P < 0.1). Multivariate analysis revealed an association between pCCA and hepatolithiasis, choledocholithiasis, DM, and heavy smoking, each, with adjusted ORs of 16.47, 9.39, 3.36 and 2.52 respectively. DM, heavy smoking, hepatolithiasis and choledocholithiasis accounted for about 22.5%, 17.1%, 8.5% and 4.8% of pCCA risk respectively (population attributable risk percentage). CONCLUSION: Our data showed that DM, heavy smoking, choledocholithiasis and hepatolithiasis were risk factors for pCCA development, implying that pCCA may share some aetiological factors with intrahepatic CCA although it has been classified as extrahepatic CCA.

Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP: prospective, randomized, double-blinded trial.

BACKGROUND AND STUDY AIM: The combination of midazolam and opioid has been widely used as a standard sedative regimen for endoscopic retrograde cholangiopancreatography (ERCP). Following recent evidence that dexmedetomidine may exert a synergistic effect in combination with midazolam, this study compared the sedative effect and adverse events of midazolam - meperidine - dexmedetomidine (MMD) and midazolam - meperidine during ERCP. PATIENTS AND METHODS: A total of 110 patients who were scheduled for ERCP were prospectively enrolled and randomly assigned, in a double-blind manner, to the MMD (n = 53) or midazolam - meperidine (n = 57) groups. Each patient received an intravenous (IV) bolus dose of midazolam and meperidine (0.06 mg/kg and 50 mg, 30 % reduction and 25 mg for patients aged ≥ 65 years, respectively). To this dose, a continuous IV infusion of dexmedetomidine (1 µg/kg/h; MMD group) or the same volume of normal saline (midazolam - meperidine group) was added. The sedation level (Ramsay Sedation Scale [RSS]) as well as hemodynamic and respiratory changes were assessed. RESULTS: Adequate sedation (RSS ≥ 3) was maintained during ERCP in 75.5 % and 36.8 % of the MMD and midazolam - meperidine group, respectively (P < 0.001). RSS scores were significantly higher in the MMD group (P < 0.001). Intraoperative bispectral index scores were significantly lower in the MMD group (P < 0.001) than in the midazolam - meperidine group. Lower additional (P = 0.001) and total (P = 0.003) doses of midazolam were required in the MMD group. Patients in the MMD group showed lower pain scores (P < 0.001) and higher satisfaction scores (P < 0.001). Desaturation occurred more frequently in the midazolam - meperidine group (11 vs. 1; P = 0.003). CONCLUSIONS: The addition of dexmedetomidine to the midazolam - meperidine regimen provided better sedative efficacy and a superior safety profile during ERCP compared with a midazolam - meperidine regimen.This trial was registered at ClinicalTrials.gov Identifier (NCT01404689).

Effect of sustained use of platelet aggregation inhibitors on post-endoscopic sphincterotomy bleeding.

BACKGROUND AND AIM: The effect of platelet aggregation inhibitors (PAI) on post-endoscopic sphincterotomy (ES) bleeding in patients who cannot discontinue PAI for sufficient time in urgent conditions has not been identified. The present study analyzed the effect of sustained use of PAI on post-procedural bleeding in patients undergoing ES. METHODS: A total of 762 patients were grouped into one of the following groups: no-PAI group (n = 601), continuation group (n = 132), and withdrawal group (n = 29). The continuation group included sustained PAI therapy (sustained user, n = 49) or those in whom therapy was interrupted <7 days prior to ES (non-sustained user, n = 83). The primary outcome was defined as the incidence, type, and severity of post-ES bleeding among groups. RESULTS: There were no significant differences between incidence, type, or severity of post-ES bleeding in the three groups. Among 132 patients with continued use of PAI, there was no significant difference regarding incidence and severity of bleeding according to sustained or non-sustained use (P = 0.071 and P = 0.086, respectively). However, post-ES delayed bleeding was more frequent in sustained PAI users than in non-sustained users (7/49, 14.3% vs 2/83, 2.4%) and was significantly associated with sustained PAI therapy in the continuation group (P = 0.013). CONCLUSION: Sustained use of PAI without interruption until ES might increase the risk of delayed bleeding.

Presence of coronary artery disease increases the risk of biliary events in patients with asymptomatic gallstones.

BACKGROUND AND AIM: Propensity score indicates a probability of having a confounding factor. It is used to match each patient with the closest propensity score between two groups, which is known as propensity score matching. This study aimed to evaluate the gallstone-related biliary events, defined as biliary colic and acute cholecystitis between coronary artery disease (CAD) and non-CAD patients using propensity score matching. METHODS: This retrospective cohort study evaluated 267 asymptomatic gallstone patients with CAD and 459 asymptomatic gallstone patients without CAD from March 2003 to December 2009 at two tertiary teaching hospitals in the Republic of Korea. After propensity score matching, total 378 patients, including 126 in study group (with CAD) and 252 in control group (without CAD), were evaluated. RESULTS: During a median follow-up of 47 months, overall gallstone-related biliary event rate was 33.5% in the study group and 27.5% in the control group. The 5-year cumulative rates were 25.3% versus 17.7% in gallstone-related biliary event and 10.9% versus 1.6% in acute cholecystitis (study versus control group). After propensity score adjustment, the risk of gallstone-related biliary events in the CAD patients significantly increased (hazard ratio 2.11, 95% confidence interval 1.14-3.90, P = 0.017 in matched patients). CONCLUSION: In patients with asymptomatic gallstones, the coexistence of CAD can increase the risk of gallstone-related biliary events, particularly acute cholecystitis. Therefore, gallstone patients with CAD should be carefully monitored, even if they are asymptomatic.

Management for CBD stone-related mild to moderate acute cholangitis: urgent versus elective ERCP.

BACKGROUND: There is no doubt that urgent biliary decompression needs to be done in case of severe acute cholangitis. However, it remains to be determined how early biliary decompression should be performed and elective intervention would be comparable to urgent intervention, in case of mild to moderate choledocholithiasis associated cholangitis. METHODS: One hundred ninety-five patients were enrolled who were diagnosed with mild to moderate cholangitis with common bile duct (CBD) stones between January 2006 and August 2010. They were divided into two groups according to door to intervention time, and urgent (≤24 h, n = 130) versus elective (>24 h, n = 82). Primary outcomes of this study were technical success rate (CBD stones removal) and clinical success rate (improvement of cholangitis) between the two groups. Hospital stay and intervention-related complications were also evaluated. RESULTS: There was no statistically significant difference in technical, clinical success rate and intervention-related complications between the urgent and elective groups (P = 0.737, 0.285, 0.398, respectively). Patients in the urgent group had significantly shorter hospitalization than in the elective group (6.8 vs. 9.2 days, P < 0.001), and furthermore, intervention to discharge time was also significantly shorter by 1.1 days in the urgent group (P = 0.035). In terms of laboratory parameters, initial CRP level was the only factor correlated with hospital stay and intervention to discharge time. CONCLUSIONS: This study demonstrates that urgent ERCP would be recommended in the management of patients with CBD stone-related mild to moderate acute cholangitis because of the advantage of short hospital stay and intervention to discharge time.

Preventive saline irrigation of the bile duct after the endoscopic removal of common bile duct stones.

BACKGROUND: Small stone fragments after an endoscopic stone extraction for choledocholithiasis may act as the nidus for recurrent choledocholithiasis. Therefore, efforts to eliminate the nidus might reduce the recurrence of choledocholithiasis and cholangitis related to choledocholithiasis. AIMS: The purpose of this study was to determine whether an additional preventive saline irrigation of the bile duct after the endoscopic removal of common bile duct stones would decrease residual stones and the recurrence of cholangitis. METHODS: A retrospective analysis was performed for the consecutively collected data about the patients who underwent the complete endoscopic treatment for common bile duct stone. RESULTS: Among 99 patients, 45 patients underwent saline irrigation. Residual stones were detected in 18 patients (18.2 %). The incidences of residual stones were 8.9 % (4 of 45 patients) in the irrigation group and 25.9 % (14 of 54 patients) in the non-irrigation group (P = 0.037). In multivariate analysis, preventive saline irrigation was found to be the only significant factor for the decrease of residual stones (HR = 0.258, P = 0.039). When analyzing the occurrence of recurrent cholangitis and the procedure related to complications, there were no significant differences according to the performance of preventive saline irrigation of the bile duct. CONCLUSIONS: Preventive saline irrigation could reduce the residual common bile duct stones without complications.

Risk factors of organ failure in patients with bacteremic cholangitis.

BACKGROUND: Bacteremic cholangitis carries a high mortality rate of up to 10 % in relation to organ failure (OF), including septic shock. AIM: The purpose of this study was to elucidate predictive factors for OF in bacteremic cholangitis. METHODS: A retrospective review of all patients diagnosed with acute cholangitis and proven bacteremia from 2003 to 2011 was performed. Comprehensive clinical and laboratory data of 211 patients were analyzed. RESULTS: There were 42 cases (19.9 %) of OF and 5 deaths (2.4 %). In the multivariate logistic regression analysis, significant predictive factors for OF were successful biliary decompression, presence of extended-spectrum beta-lactamase organism (ESBL), higher total bilirubin, and higher blood urea nitrogen (BUN) level at admission with odds ratios (ORs) of 0.129, 6.793, 1.148, and 1.089, respectively. Subgroup analysis of 165 patients who underwent biliary decompression before an event (with OF: 20, without OF: 145) was performed to elucidate the risk factors for organ failure even after successful biliary drainage. Variables significantly associated with OF included ESBL and BUN (OR = 4.123 and 1.177, respectively). We developed a scoring system with regression coefficient of each significant variable. The organ failure score was calculated using the following equation: (1.4 × ESBL) + (0.2 × BUN). This scoring system for predicting OF was highly sensitive (85.0 %) and specific (83.4 %). CONCLUSIONS: Biliary decompression, ESBL, total bilirubin, and BUN are prognostic determinants in patients with bacteremic cholangitis. An organ failure scoring system may allow clinicians to identify groups with poor prognosis even after successful biliary decompression.

SiO-induced thermal instability and interplay between graphite and SiO in graphite/SiO composite anode.

Silicon monoxide (SiO), which exhibits better cyclability compared to silicon while delivering higher capacity than that of graphite, is an adequate material for the development of lithium-ion batteries (LIBs) having higher energy densities. However, incorporating silicon-based materials including SiO into stable graphite anode inevitably degrades not only cycle life but also calendar life of LIBs, while little is known about their aging mechanisms. Here, SiO-induced thermal instability of the graphite/SiO composite anode is investigated. We reveal that under thermal exposure, SiO accelerates the loss of lithium inventory and concomitantly facilitates the lithium de-intercalation from graphite. This self-discharge phenomenon, which is weakly observed in the graphite anode without SiO, is the result of preferential parasitic reaction on the SiO interface and spontaneous electron and lithium-ion migration to equilibrate the electron energy imbalance between graphite and SiO. Understanding this underlying electron-level interplay between graphite and SiO in the composite anode will contribute toward improving shelf life of SiO-containing LIBs in actual operating conditions.

LC3B is an RNA-binding protein to trigger rapid mRNA degradation during autophagy.

LC3/ATG8 has long been appreciated to play a central role in autophagy, by which a variety of cytoplasmic materials are delivered to lysosomes and eventually degraded. However, information on the molecular functions of LC3 in RNA biology is very limited. Here, we show that LC3B is an RNA-binding protein that directly binds to mRNAs with a preference for a consensus AAUAAA motif corresponding to a polyadenylation sequence. Autophagic activation promotes an association between LC3B and target mRNAs and triggers rapid degradation of target mRNAs in a CCR4-NOT-dependent manner before autolysosome formation. Furthermore, our transcriptome-wide analysis reveals that PRMT1 mRNA, which encodes a negative regulator of autophagy, is one of the major substrates. Rapid degradation of PRMT1 mRNA by LC3B facilitates autophagy. Collectively, we demonstrate that LC3B acts as an RNA-binding protein and an mRNA decay factor necessary for efficient autophagy.

TRIM28 functions as a negative regulator of aggresome formation.

Selective recognition and elimination of misfolded polypeptides are crucial for protein homeostasis. When the ubiquitin-proteasome system is impaired, misfolded polypeptides tend to form small cytosolic aggregates and are transported to the aggresome and eventually eliminated by the autophagy pathway. Despite the importance of this process, the regulation of aggresome formation remains poorly understood. Here, we identify TRIM28/TIF1ß/KAP1 (tripartite motif containing 28) as a negative regulator of aggresome formation. Direct interaction between TRIM28 and CTIF (cap binding complex dependent translation initiation factor) leads to inefficient aggresomal targeting of misfolded polypeptides. We also find that either treatment of cells with poly I:C or infection of the cells by influenza A viruses triggers the phosphorylation of TRIM28 at S473 in a way that depends on double-stranded RNA-activated protein kinase. The phosphorylation promotes association of TRIM28 with CTIF, inhibits aggresome formation, and consequently suppresses viral proliferation. Collectively, our data provide compelling evidence that TRIM28 is a negative regulator of aggresome formation.Abbreviations: BAG3: BCL2-associated athanogene 3; CTIF: CBC-dependent translation initiation factor; CED: CTIF-EEF1A1-DCTN1; DCTN1: dynactin subunit 1; EEF1A1: eukaryotic translation elongation factor 1 alpha 1; EIF2AK2: eukaryotic translation initiation factor 2 alpha kinase 2; HDAC6: histone deacetylase 6; IAV: influenza A virus; IP: immunoprecipitation; PLA: proximity ligation assay; polypeptidyl-puro: polypeptidyl-puromycin; qRT-PCR: quantitative reverse-transcription PCR; siRNA: small interfering RNA.

A High Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis in Patients with Advanced Gallbladder Cancer Receiving Chemotherapy.

BACKGROUND: Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to be prognostic markers in various cancers. However, the prognostic value of these inflammatory biomarkers, particularly MLR, in gallbladder cancer remains to be determined. METHODS: From 2005 to 2016, 178 patients with histologically confirmed gallbladder adenocarcinoma who underwent palliative chemotherapy were queried in this study. The association between survival and various clinical and laboratory variables, including MLR, NLR, and PLR, was investigated. The optimal cutoff values for MLR, NLR, and PLR were determined using the maxstat package of R. RESULTS: Patients with high MLR (>0.24) were expected to have shorter progression-free survival [PFS; hazard ratio (HR), 2.100; 95% confidence interval (CI), 1.397-3.157; P < 0.001] and overall survival (OS; HR, 2.533; 95% CI, 1.664-3.856; P < 0.001) compared with patients with low MLR (≤0.24). In multivariate Cox model, CA 19-9, stage, and MLR were independent factors for PFS. MLR was also an independent predictor of OS along with PLR, age, and CA 19-9, whereas NLR was not significantly associated with OS. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve of MLR for predicting OS was greater than that of NLR and PLR at most time points. CONCLUSIONS: MLR independently predicts survival in gallbladder cancer patients undergoing chemotherapy. Future prospective studies are needed to validate its value as a prognostic biomarker. IMPACT: MLR is an inexpensive and easily available biomarker for predicting prognosis in patients with gallbladder cancer undergoing chemotherapy.

Tumor Marker Kinetics as Prognosticators in Patients with Unresectable Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy.

BACKGROUND/AIMS: To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy. METHODS: One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates. RESULTS: Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up. CONCLUSIONS: CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy.

Central Obesity as a Risk Factor for Non-Erosive Reflux Disease.

PURPOSE: Although central obesity is a risk factor for erosive esophagitis, information regarding the association between central obesity and non-erosive reflux disease (NERD) is still scarce. The purpose of this study was to investigate the risk factors for NERD by comparing NERD patients and healthy controls. MATERIALS AND METHODS: Comprehensive clinical data from 378 patients who underwent esophagogastroduodenoscopy from December 2012 to May 2013 and had no visible esophageal mucosal breakage were analyzed. The Korean version of GerdQ questionnaire was used to diagnose NERD. The association between central obesity and NERD was assessed after matching subjects according to propensity scores. RESULTS: There were 119 NERD patients and 259 controls. In multivariate analysis, central obesity, female gender, and younger age were significantly associated with NERD [odds ratio (OR)=2.55, 1.93, and 1.80; p=0.001, 0.005, and 0.011, respectively]. After adjusting for 12 clinical variables using propensity score matching, 114 NERD patients were matched to 114 controls. All variables were well balanced between the two groups (average D before matching: 0.248, after matching: 0.066). Patients with NERD were more likely to have central obesity than healthy controls (28.1% vs. 7.9%). After adjusting for propensity scores and all covariates in multivariable logistic regression analyses, central obesity was still found to be a significant risk factor for NERD (OR=4.55, p<0.001). CONCLUSION: Central obesity appears to be an independent risk factor for NERD. This result supports the presence of an association between GERD and central obesity, even in the absence of esophageal erosion (NERD).