The relationship between bile reflux and common bile duct diameter after cholecystectomy: a clinical case-control study.

OBJECTIVE: The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy. MATERIALS AND METHODS: In our case series analysis, according to the endoscopy results, the patients who underwent cholecystectomy were divided into two groups as those with BR and those non-BR. Age, sex, CBD diameter measured on ultrasonography, computed tomography, magnetic resonance cholangiopancreatography, and endoscopic biopsy results of the patients were statistically analyzed. RESULTS: In a total of 188 patients included in the study, BR was detected in 93 patients, it was not observed in 95 patients. The CBD diameter of the patients was observed to be 7 mm or less in 70.9% (n = 66) in the BR group, and 23% (n = 22) in the non-BR group. The statistical analysis revealed that while there was a significant difference between the two groups in terms of CBD diameter and intestinal metaplasia, the results were similar in both groups in terms of inflammation, activity, atrophy, and Helicobacter pylori. CONCLUSION: We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy.

OBJETIVO: Investigar la relación entre el reflujo biliar y el diámetro del colédoco después de la colecistectomía. MÉTODO: Estudio retrospectivo en el que, de acuerdo con los resultados de la endoscopia, los pacientes que se sometieron a colecistectomía se dividieron en dos grupos: con reflujo biliar y sin reflujo biliar. Se analizaron estadísticamente la edad, el sexo, el diámetro del conducto biliar común medido por ultrasonografía, tomografía computarizada y colangiopancreatografía por resonancia magnética, y los resultados de la biopsia endoscópica. RESULTADOS: En un total de 188 pacientes incluidos en el estudio, se detectó reflujo biliar en 93 pacientes y no se observó en 95 pacientes. Se vio que el diámetro del conducto biliar común de los pacientes era de 7 mm o menos en el 70.9% (n = 66) del grupo con reflujo biliar y en el 23% (n = 22) del grupo sin reflujo biliar. El análisis estadístico reveló que, si bien hubo una diferencia significativa entre los dos grupos en términos de diámetro del conducto biliar común y metaplasia intestinal, los resultados fueron similares en ambos grupos en términos de inflamación, actividad, atrofia y presencia de Helicobacter pylori. CONCLUSIONES: Creemos que el diámetro del colédoco puede ser un factor predictivo en la detección de reflujo biliar después de la colecistectomía.

HIDA and Seek: Challenges of Scintigraphy to Diagnose Bile Reflux Post-Bariatric Surgery.

INTRODUCTION: Oesophageal bile reflux after bariatric surgery may trigger development of Barrett's oesophagus. Gastro-oesophageal reflux of bile is captured by hepatobiliary iminodiacetic acid (HIDA) scintigraphy; however, anatomical and physiological changes after bariatric surgery warrant protocol modifications to optimise bile reflux detection. METHODS: HIDA scintigraphy occurred 6 months after either sleeve gastrectomy, Roux-en-Y gastric bypass or one-anastomosis gastric bypass. Standard HIDA scanning involves (i) 6-h fast and 24-h abstinence from opioids; (ii) IV administration of 99mTc di-isopropyl iminodiacetic acid; and (iii) dual anterior/posterior 60-min dynamic scanning of the duodenum, stomach and oesophagus. Three challenges were identified, and modifications were implemented, namely, (1) anatomical localisation of refluxed bile on planar scintigraphy was improved by adding a SPECT/CT for 3D imaging; (2) impaired cholecystokinin-controlled gallbladder emptying, following bypassed duodenum, was addressed by ingestion of a 'fatty meal'; and (3) intestinal hypomotility after gastric bypass was counteracted by longer scan duration (75-90 min) to allow bile to pass beyond the gastro-jejunal anastomosis. RESULTS: HIDA scan was undertaken in 18 patients, 13 of whom underwent the modified protocol. The tailored protocol ameliorated issues identified with the standard HIDA scan protocol; thus, accurate anatomical localisation was achieved in all patients, no delayed gallbladder emptying was observed, and bile was observed beyond the gastro-jejunal anastomosis in all gastric bypass patients. The modified technique was well tolerated by patients. CONCLUSION: A tailored HIDA scan protocol with addition of a SPECT-CT scan, ingestion of a fatty meal and prolonged scanning duration results in enhanced bile reflux detection in post-bariatric surgical patients.

Duodenogastric biliary reflux assessed by scintigraphic scan in patients with reflux symptoms after sleeve gastrectomy: preliminary results.

BACKGROUND: Bile reflux is a factor in the appearance of severe esophagitis and Barrett's esophagus, which have been reported after sleeve gastrectomy (SG). Incompetent lower esophageal sphincter and increased gastroesophageal acid reflux have been demonstrated after this operation. Some reports have shown bile content in the antrum during endoscopic control, but no investigations objectively confirm the presence of duodenogastric bile reflux in these patients. OBJECTIVES: To evaluate the presence of duodenogastric bile reflux (DGR) after SG in patients presenting reflux symptoms. SETTING: University hospital. METHODS: Prospective study of 22 patients presenting reflux symptoms who underwent SG for morbid obesity and who received endoscopic evaluation and scintigraphic study to confirm esophagitis and duodenogastric bile reflux. RESULTS: Erosive esophagitis was observed in 11 patients and Barrett's esophagus in 2 patients. Seven patients (31.8%) presented positive DGR. Among them, 3 had type B and C esophagitis. The other 4 patients did not present esophagitis in spite of reflux symptoms. CONCLUSION: DGR may be present in patients with gastroesophageal reflux after SG. This line of investigation requires further studies to confirm this hypothesis.

Gallbladder mucosal lesions associated with high biliary amylase irrespective of pancreaticobiliary maljunction.

BACKGROUND: Previous studies have focused on the presence of reflux in selected cohorts with pancreaticobiliary maljunction (PBM), but little is known regarding the wider incidence of occult reflux and associated mucosal changes. We aimed to correlate gallbladder mucosal abnormalities with objective evidence of PBM and occult pancreaticobiliary reflux (PBR) in an Australian population undergoing cholecystectomy. METHODS: Patients undergoing cholecystectomy between September 2010 and September 2012 were eligible for inclusion. Demographic and pre-operative clinical data were collated and entered into a pre-defined database. Operative cholangiograms were routinely performed and the presence of PBM noted. Gallbladder bile samples were analysed for bilirubin (<20 µmol/L), amylase (<100 U/L) and lipase (<70 U/L) levels. Evidence of PBR was correlated with gallbladder mucosal findings. RESULTS: A total of 305 cholecystectomies were performed for biliary colic (73%), choledocholithiasis (9%), cholecystitis (8.4%) and pancreatitis (6.4%). A total of 12.7% had cholangiographic evidence of PBM and 11.9% possessed gallbladder mucosal changes. Overall, 7.7% had increased biliary amylase, which was associated with significantly higher rates of gallbladder intestinal metaplasia (33% versus 8.6%; P = 0.012). Elevated biliary amylase was also higher in patients with prior pancreatitis (P = 0.02) or choledocholithiasis (P < 0.01). The presence of PBM did not predict for the presence of PBR. CONCLUSION: PBR is associated with an increased frequency of gallbladder mucosal metaplasia, irrespective of the presence of PBM. Objectively identified reflux represents an additional indication for cholecystectomy but the long-term consequences for extra-hepatic biliary malignancy remain unknown and warrant further investigation. Methods of objectively identifying PBR pre-operatively require further investigation.

Correlation Between Bile Reflux Gastritis and Biliary Excreted Contrast Media in the Stomach.

OBJECTIVE: This study aimed to evaluate the relationship between biliary excreted contrast media in the stomach and the presence of bile reflux gastritis. METHODS: Consecutive 111 patients who underwent both gadoxetic acid-enhanced magnetic resonance cholangiography (gadoxetic MRC) and gastric endoscopy were included in this study. We performed a review of the gadoxetic-MRC image sets acquired 60 minutes after intravenous injection of contrast media and endoscopic images. We recorded amount of contrast media in the stomach. The sensitivity, specificity, and accuracy of duodenogastric bile reflux diagnosis were evaluated for the gadoxetic MRC. Statistical analysis was performed using the Fisher exact test and the linear-by-linear association test. RESULTS: Among the 111 patients, 39 had 60-minute delayed images showing the presence of contrast media in the stomach. Of these 39 patients, 13 had bile reflux gastritis and 5 showed bile in the stomach without evidence of erythematous gastritis. Of the 72 patients who did not show contrast media in the stomach, none had bile reflux gastritis and 2 patients showed bile staining in the stomach without evidence of erythematous gastritis. Bile reflux gastritis was significantly more frequent in patients with contrast media in the stomach on gadoxetic MRC than in those without. Patients with high-grade extension of contrast media in the stomach had significantly frequent bile reflux gastritis than did those with low-grade extension. CONCLUSION: Biliary excreted contrast media in the stomach on 60-minute delayed gadoxetic MRC has a correlation with the presence of bile reflux gastritis on endoscopic examination.

Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma.

BACKGROUND: Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. METHODS: Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. RESULTS: Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. CONCLUSIONS: Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development.

Pancreaticobiliary Juice Reflux in Patients With a Morphologically Normal Ductal System: Assessment Using Unenhanced MRI With Spin Labeling.

OBJECTIVE: The purpose of this article is to evaluate pancreaticobiliary reflux and to assess its correlation with clinical findings in patients without morphologic pancreaticobiliary maljunction by using a new MRI technique. MATERIALS AND METHODS: A total of 320 consecutive patients with suspected pancreaticobiliary diseases underwent MRCP and flow analysis by MRI. MRI flow analysis, clinical, and laboratory findings of each patient were retrospectively reviewed. The visible pancreaticobiliary reflux was graded on a 5-point confidence scale. RESULTS: Among all 320 patients with pancreatic juice reflux, 14.1% had reflux scored as grades 4 and 5 combined, and 5.0% had reflux scored as grade 5. By univariate analysis and multivariate analysis, a relatively long common channel was found to be the only significant causal factor for pancreatic juice reflux. Of patients with pancreatic juice reflux of grade 4 or 5, 11.1% (5/45) also had biliary malignancies; 18.8% (3/16) of those with pancreatic juice reflux of grade 5 had biliary malignancies. Conversely, pancreatic juice reflux of grade 4 or 5 occurred in 35.7% (5/14) of patients with biliary malignancies, and reflux of grade 5 occurred in 21.4% (3/14) of those patients. CONCLUSION: It was possible to evaluate pancreaticobiliary reflux using an MRI technique that may be suitable as a screening tool. Our results revealed that pancreaticobiliary reflux is relatively frequent in individuals without pancreaticobiliary maljunction.

Incidental pathologic extracardiac uptake of (99m)Tc-tetrofosmin in myocardial perfusion imaging: Importance of patient background evaluation.

(99m)Tc-tetrofosmin single photon emission computed tomography ((99m)Tc-tetrofosmin SPECT) has an important role in the assessment of coronary artery disease. Despite being its main indication, this study does not only evaluate myocardial perfusion, but much more. Moreover, during the SPECT acquisition, the field area covered includes many important organs of the thorax and abdomen, so extracardiac abnormalities can be observed. The correct etiologic diagnosis of them is only possible if we understand how (99m)Tc-tetrofosmin works and make a comprehensive investigation of the clinical history of the patient.

Clinical significance of bile reflux into the pancreatic duct without pancreaticobiliary maljunction assessed by intraoperative cholangiography.

INTRODUCTION: Bile reflux into the pancreatic duct (BRPD) is sometimes demonstrated during intraoperative cholangiography (IOC) even in patients without pancreaticobiliary maljunction. However, the clinical significance of this finding in laparoscopic and open cholecystectomy is unclear. METHODS: Among 484 patients who underwent cholecystectomy (372 laparoscopic, 112 open), patients whose pancreatic duct was depicted in IOC were selected. The value of pancreatic amylase (p-amylase) of the gallbladder bile, histological changes, and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in the gallbladder mucosa were analyzed in patients with BRPD. The data were then compared to those in patients without BRPD whose gallbladder bile p-amylase was measured (control group, n = 20). RESULTS: The success rate of IOC was 93.6%. The rate of BRPD in laparoscopic and open cholecystectomy was 5.2% and 5.7%, respectively. The value of gallbladder bile p-amylase in patients with BRPD was significantly higher than in the control group (790.5 vs 14.0 IU/L, P = 0.034). The value of the PCNA labeling index in patients with BRPD was significantly higher than that of the control group (15.4% vs 4.1%, P = 0.0026). Among the 24 patients with BRPD, pathological changes in the gallbladder mucosa were detected in five (two hyperplasia, three metaplasia), but there was no correlation between the presence of pathological change and PCNA labeling index or gallbladder bile p-amylase. CONCLUSIONS: IOC could detect BRPD both in laparoscopic and open cholecystectomy at a similar rate. Patients with BRPD had high levels of gallbladder bile p-amylase and PCNA labeling index, findings similar to those in patients with pancreaticobiliary maljunction.

Evaluation of bile reflux in HIDA images based on fluid mechanics.

We propose a new method to help physicians assess, using a hepatobiliary iminodiacetic acid scan image, whether or not there is bile reflux into the stomach. The degree of bile reflux is an important index for clinical diagnosis of stomach diseases. The proposed method applies image-processing technology combined with a hydrodynamic model to determine the extent of bile reflux or whether the duodenum is also folded above the stomach. This condition in 2D dynamic images suggests that bile refluxes into the stomach, when endoscopy shows no bile reflux. In this study, we used optical flow to analyze images from Tc99m-diisopropyl iminodiacetic acid cholescintigraphy (Tc99m-DISIDA) to ascertain the direction and velocity of bile passing through the pylorus. In clinical diagnoses, single photon emission computed tomography (SPECT) is the main clinical tool for evaluating functional images of hepatobiliary metabolism. Computed tomography (CT) shows anatomical images of the external contours of the stomach, liver, and biliary extent. By exploiting the functional fusion of the two kinds of medical image, physicians can obtain a more accurate diagnosis. We accordingly reconstructed 3D images from SPECT and CT to help physicians choose which cross sections to fuse with software and to help them more accurately diagnose the extent and quantity of bile reflux.

Analysis of esophageal reflux after proximal gastrectomy measured by wireless ambulatory 24-hr esophageal pH monitoring and TC-99m diisopropyliminodiacetic acid (DISIDA) scan.

BACKGROUND AND OBJECTIVES: Reflux is one of the most common sequela after proximal gastrectomy (PG). The aim of this study was to find a predicting factor related to the character of esophageal reflux after PG. METHODS: Wireless ambulatory 24-hr pH monitoring (for acid reflux, AR) and diisopropyliminodiacetic acid hepatobiliary scan (for bile reflux, BR) were performed on 24 patients who had reflux symptoms after PG with esophagogastrostomy from July 2008 to March 2009. Endoscopic examination was done and the length of remnant stomach (LoRS) was measure by postoperative UGI series. RESULTS: Eleven patients (45.8%) had only BR, 7 (29.2%) had AR only, Two patients (8.3%) had both acid and BR, and 3 (12.5%) had neither. The LoRS along greater curvature was significantly shorter in patients with only BR (16.11 +/- 2.87 cm) than in patients with only AR (23.69 +/- 6.15 cm, P = 0.003). Severity of symptoms or esophagitis was not significantly correlated with the content of acid or BR. CONCLUSION: Reflux symptom after PG is caused by either bile or acid rather than both. Character of reflux was related to the LoRS.

Western blotting in the diagnosis of duodenal-biliary and pancreaticobiliary refluxes in biliary diseases.

BACKGROUND: Currently adopted diagnostic methods for duodenal-biliary and pancreaticobiliary refluxes carry many flaws, so the incidence of the two refluxes demands further larger sample size studies. This study aimed to evaluate Western blotting for the diagnosis of refluxes in biliary diseases. METHODS: An oral radionuclide 99mTc-DTPA test (radionuclide, RN) was conducted for the observation of duodenal-biliary reflux prior to measuring bile radioactivity and Western blotting for detecting bile enterokinase (EK). Pancreaticobiliary reflux was assessed by biochemical and Western blotting tests for biliary amylase activity and trypsin-1, respectively. In accordance with bile sample origin, our samples were classified into ductal bile and gall bile groups; based on each individual biliary disease, we further classified the ductal bile group into five sub-groups, and the gall bile group into four sub-groups. Western blotting was conducted to assess the two refluxes in biliary diseases. RESULTS: Consistencies were noted between EK and RN tests when diagnosing duodenal-biliary reflux (P<0.001). The amylase and trypsin-1 tests also showed consistency in diagnosing pancreaticobiliary reflux (P<0.001). Amylase and lipase levels within gall and ductal bile were strongly correlated (P<0.05). In the common bile duct pigment stone group, the EK and trypsin-1 positive rates were found to be insignificant (P>0.05); in the common bile duct cyst group, the EK positive rate was significantly lower than the trypsin-1 positive rate (P<0.05). CONCLUSIONS: Western blotting can accurately reflect duodenal-biliary and pancreaticobiliary refluxes. EK has greater sensitivity than RN for duodenal-biliary reflux. The majority of biliary amylase and lipase comes from the pancreas in all biliary diseases; pancreaticobiliary reflux is the predominant source in the common bile duct cyst group and duodenal-biliary reflux is responsible for the ductal pigment stone group.

Dynamic study of pancreaticobiliary reflux using secretin-stimulated magnetic resonance cholangiopancreatography in patients with choledochal cysts.

BACKGROUND/PURPOSE: Refluxes through pancreaticobiliary maljunctions play an important role in the pathophysiology of choledochal cysts. Dynamic studies of the pancreaticobiliary tract were performed using secretin-stimulated magnetic resonance cholangiopancreatography. METHODS: Six patients with choledochal dilation were recruited for this study. Four patients exhibited cystic and 2 exhibited fusiform dilatation of the common bile duct (CBD). Magnetic resonance cholangiopancreatography images were obtained every minute during the 15-minute period after secretin stimulation. The sequential morphological changes in the biliary trees, pancreas, and duodenum were assessed, and the total pixel values of these organs were measured for each image, then plotted as a ratio against the baseline image. RESULTS: In 2 cases involving cystic dilatation, the intensity of bile duct images continued to rise after secretin stimulation. In a case involving fusiform dilatation, a transitory elevation in CBD intensity was observed. In 3 cases involving fusiform or cystic dilatation, the intensity of CBD did not change notably. In all cases, the duodenum was filled well after secretin stimulation. CONCLUSIONS: The sustained elevation in bile duct intensity after secretin stimulation indicates reflux and bile stasis. Transitory elevation may indicate reflux without stasis. This method allows assessment of the dynamics of pancreatic and bile fluid under more physiologic condition.

Sonographic demonstration of duodenobiliary reflux with soda enhancement.

Cholangitis rarely occurs after sphincteroplasty if there is no biliary obstruction. We report the case of a patient who developed recurrent cholangitis despite having a patent biliary tract after sphincteroplasty. Duodenobiliary reflux was demonstrated on sonography after enhancement of the reflux flow with a novel oral contrast agent, a carbonated soda beverage. Sonography with contrast enhancement provided by soda solution may prove satisfactory to detect duodenobiliary reflux after sphincteroplasty safely, effectively, and economically.

Dual-radionuclide simultaneous biliary and gastric scintigraphy to depict surgical treatment of bile reflux.

Biliary diversion procedures are performed during gastric surgery to decrease bile reflux. A 1-day dual-radionuclide examination was studied to determine its potential in the evaluation of the effectiveness of the Braun enteroenterostomy in reducing bile reflux and its effects on gastric emptying. Orally ingested gallium 67-labeled egg and intravenously administered technetium 99m diisopropyl-imino-diacetic acid were imaged simultaneously. This provided a way to depict both bile reflux and gastric emptying on the same day in patients who underwent gastric surgery. Overall, the Braun enteroenterostomy trades bile reflux, a symptomatic and premalignant disease, for gastroparesis, a less severe and often treatable disease.

Duodenogastric bile reflux after gastric bypass: a cholescintigraphic study.

In this exploratory study, we examined the occurrence of duodenogastric bile reflux to the excluded stomach after Roux-en-Y gastric bypass, a standard surgical therapy for morbid obesity. We studied 22 unselected patients (median age 44, 20 females) 18 months postoperatively. BMI at surgery and cholescintigraphy was 45 and 29 kg/m2, respectively. Mebrofenin labeled with 200 MBq 99mT was injected intravenously and the fate of radioactivity followed for 90 min. Bile flow was enhanced with cholecystokinin. We found scintigraphic evidence of duodenogastric bile reflux in 36% of the patients. The tracer remained in the excluded stomach throughout the study period. In conclusion, our investigation indicates that in more than one third of the patients undergoing gastric bypass, the gastric mucosa in the excluded stomach is exposed to the potential deleterious effects of bile.

New insight into bile flow dynamics in anomalous arrangement of the pancreaticobiliary duct.

BACKGROUND: In an anomalous arrangement of the pancreaticobiliary duct (AAPBD), two-way regurgitation, including pancreaticobiliary reflux and biliopancreatic reflux (BPR), might occur. Although pancreaticobiliary reflux has been shown by high levels of pancreatic enzymes in bile, there have been few reports of clinical evidence of BPR in AAPBD. Recently, spiral computed tomography combined with intravenous infusion cholangiography (IVC-SCT) has been reported to be useful for visualizing the biliary anatomy, which may allow a new insight into bile flow dynamics in AAPBD. METHODS: Fifteen paediatric patients with AAPBD were examined before operation using both IVC-SCT and endoscopic retrograde cholangiopancreatography. Visualization of the main pancreatic duct on IVC-SCT defined the presence of BPR. Blood samples were also analysed when the initial symptom was strongly present. RESULTS: BPR was observed in six of 15 patients. Pancreatic enlargement and hyperamylasaemia were significantly more frequent in patients without BPR than in those with BPR. Levels of enzyme markers of cholestasis were also higher in the former group. CONCLUSION: The present study, using IVC-SCT, has identified clinical evidence of BPR in AAPBD. Further studies are necessary to determine the correlation between BPR and clinical manifestations.

Cholangitis associated with cystic dilatation of the intrahepatic bile ducts after antireflux valve construction in biliary atresia.

An intussusception-type antireflux valve (ARV) has been introduced to prevent postoperative ascending cholangitis in the management of biliary atresia (BA). We investigated the characteristics of cholangitis in the management of BA using the ARV in 38 patients who had undergone an operation at our institution; 29 underwent ARV construction at the same time as portenterostomy (PEO) or hepaticojejunostomy. One patient underwent ARV construction for refractory cholangitis with cystic dilatation of the intrahepatic bile ducts (CDIB) long after the PEO. Five of 29 patients who had ARV construction developed CDIB complicated by severe, refractory cholangitis. One or two episodes of mild cholangitis were observed in 5 (20.8%) of 24 patients who did not show CDIB. An ARV created for postoperative recurrent cholangitis associated with CDIB was ineffective. Preoperative cholangitis associated with a type I choledochal cyst and CDIB was observed in 1 patient. In conclusion, the ARV was effective in preventing refractory cholangitis without CDIB, but ineffective in preventing cholangitis with CDIB. Our findings suggest that CDIB resulting from the ongoing process of BA could be a potential target of bacterial infection through other routes than bilioenteric reflux.