Distinct Physiological Characteristics of Isolated Laryngopharyngeal Reflux Symptoms.

BACKGROUND & AIMS: Patients with isolated laryngopharyngeal reflux symptoms (LPRS) defined as those without concomitant typical reflux symptoms (CTRS) are clinically challenging to manage due to unclear pathophysiology. We investigated esophageal physiology in patients with isolated LPRS and their response to proton-pump inhibitors (PPI) therapy. METHODS: This is a multi-center observational study conducted in referral hospitals in Taiwan. Patients with predominant LPRS, but without common non-reflux causes, underwent esophageal manometry, 24-hr ambulatory esophagopharyngeal pH testing, and Bernstein test, followed by a 12-week esomeprazole 40 mg twice-daily treatment. Participants with pathological reflux were divided into the isolated LPRS group (ie, LPRS without CTRS, n = 40) and the CTRS group (ie, LPRS with CTRS, n = 66). Participants without pathological reflux or esophagitis (n = 132) served as the nonreflux controls. RESULTS: The PPI-responsiveness was similar between the isolated LPRS group and CTRS group (63% vs 57%, P = .8), but lower in the nonreflux controls (32%, P = .005). Despite similar distal esophageal acid exposure time (P = .7) when compared to those with CTRS, the isolated LPRS group had a lower prevalence of both positive Bernstein test (P = .001) and ineffective esophageal motility disorder (P = .03), and fewer pharyngeal acid reflux episodes (P < .0001). CONCLUSIONS: Our findings indicate similar distal esophageal acid exposure and PPI-responsiveness between LPRS patients with and without CTRS. The lack of CTRS in the isolated LPRS group is likely due to esophageal acid hyposensitivity and fewer pharyngeal acid reflux episodes, thus implicating distinct pathophysiology of isolated LPRS from those with CTRS.

Responder Definition of a Patient-Reported Outcome Instrument for Laryngopharyngeal Reflux Based on the US FDA Guidance.

BACKGROUND: Different end-point measures may contribute to inconsistent therapeutic responses in relief of laryngopharyngeal reflux (LPR) symptoms. OBJECTIVES: We aimed to determine an a priori responder definition for a patient-reported outcome instrument, the Reflux Symptom Index (RSI), using an anchor-based method, to interpret individual treatment benefit in patients with LPR, on the basis of the US Food and Drug Administration guidance. METHODS: Patients with chronic laryngeal symptoms suggestive of LPR underwent twice-daily 40 mg esomeprazole treatment for 12 weeks. We used a 50% or more reduction in the primary laryngeal symptom at week 12, an empirical criterion, as an anchor to dichotomize the participants into two groups, and to establish a responder definition of the RSI score change. The optimal cutoff point of the RSI score change was determined on the basis of the maximal Youden index of the receiver operating characteristic analysis. RESULTS: The mean reduction in the RSI score was significantly greater in subjects with a 50% or more reduction in the primary laryngeal symptom than in those without (-11.0 ± 7.8 vs. -3.1 ± 8.3, P < 0.0001). A reduction of six points or more in the RSI score at week 12 was considered to be the responder definition with a sensitivity of 0.79 and a specificity of 0.70. CONCLUSIONS: We propose an a priori responder definition derived from an empirical criterion according to the Food and Drug Administration guidance: a reduction of six points or more in the RSI score at week 12. This preliminary estimate provides a clinically meaningful change at an individual level, although additional studies and validations across various languages are required.

Impact of Overlapping Functional Gastrointestinal Disorders on the Presentation and Quality of Life of Patients with Erosive Esophagitis and Nonerosive Reflux Disease.

OBJECTIVE: The aim of this study was to investigate the impact of overlapping functional gastrointestinal disorder (FGID) on the quality of life of patients with nonerosive reflux disease (NERD) and erosive esophagitis (EE). MATERIALS AND METHODS: Data from patients with NERD and EE were collected between January 2009 and March 2010. These cases were further stratified into the subgroups of overlapping NERD-functional dyspepsia (FD), NERD-irritable bowel syndrome (IBS), EE-FD, EE-IBS, and NERD or EE alone according to the symptoms. All patients completed the modified Chinese GERDQ and the SF-36 questionnaires. RESULTS: Of the 222 enrolled patients, 96 (43.2%) had NERD and 126 (56.8%) had EE. Overlap of FGID occurred in 43.8-45.8% of the NERD patients, and in 41.3-44.4% of EE cases. The impact of overlapping FGID on patient quality of life was greater in the patients with overlapping NERD-FD compared to those with NERD alone (mean SF-36 total scores 59 vs. 72, adjusted p = 0.025) and the cases with overlapping EE-FD compared to those with EE alone (mean SF-36 total scores 53.19 vs. 73.11, adjusted p = 0.047). There were no significant differences between the individuals with overlapping NERD/EE-IBS and those with NERD/EE alone. CONCLUSIONS: There was a high prevalence of overlapping FGID, with both FD and IBS, among the GERD patients. The individuals with overlapping GERD and FD had lower quality of life scores than those with GERD alone.

The impact of acid-suppressing drugs to the patients with chronic obstructive pulmonary disease: A nationwide, population-based, cohort study.

BACKGROUND: A high prevalence of gastroesophageal reflux disease symptoms has observed among chronic obstructive pulmonary disease (COPD) patients, and proton-pump inhibitors (PPIs) are the main medication in clinical practices. The aim of this study is to analyze the impact of PPIs to the risk of pneumonia in the cases with COPD. MATERIALS AND METHODS: This was a nationwide, population-based, cohort study using National Health Insurance Program in Taiwan. The enrolled cases were newly-diagnosed COPD, older than 30 years, between 2001 and 2005. Patients' prescriptions with PPIs and histamine receptor 2 antagonists (HR2As), >2 months, were identified. The appearance of pneumonia and mortality of these enrolled patients was recorded. Multivariate Cox's regression was used to examine the influence of acid-suppressing drugs to pneumonia on individuals with COPD. RESULTS: A total of 17,498 patients were included, of whom 109 (0.6%) and 526 (3%) cases had used PPIs and HR2As respectively. The risk of pneumonia existed when patients had used concurrent PPIs (adjusted hazard ratio [HR] = 1.76; 95% confidence interval [CI] = 1.33-2.34) or HR2As (adjusted HR = 1.25; 95% CI = 1.07-1.47). The positive association was lost in the cases over 70 years. The ratio of mortality also increased in those with PPIs or HR2As. CONCLUSION: Acid-suppressing drugs, especially PPIs, are attributed to more pneumonia happening in COPD patients compare with nonusers. The association was lost in elderly cases. Use acid-suppressing drugs should be careful about a higher possibility of pneumonia in younger individuals with COPD.

Factors influencing treatment outcome in patients with gastroesophageal reflux disease: outcome of a prospective pragmatic trial in Asian patients.

BACKGROUND: Predicting response to proton pump inhibitor (PPI) treatment can aid the effective management of gastroesophageal reflux disease (GERD). The aim was to investigate the predictors of symptomatic response to pantoprazole in Asian patients with GERD; the first study of its kind in Asian patients. METHODS: Asian patients with GERD symptoms (N = 209) received pantoprazole 40 mg daily for 8 weeks in a multinational, prospective, open-label study. Response was assessed using ReQuest™. Baseline and demographic factors were examined using logistic regression to determine if they were related to treatment response. RESULTS: Response rates were 44.3% (Week 4) and 63.6% (Week 8) in Asian patients versus 60.7% (P < 0.001) and 72.2% (P = 0.010) for the rest of the world. Higher response rates at 8 weeks occurred in patients with erosive reflux disease (ERD; 71.3%) versus those with non-erosive reflux disease (NERD) at baseline (48.5%). The presence of ERD (P = 0.0143) and lower ReQuest™-GI scores at baseline (P = 0.0222) were associated with response. Improvements in quality of life (QoL) and anxiety and depression at 4 and 8 weeks were associated with treatment response (both P < 0.0001). Patient satisfaction correlated with treatment response (P < 0.0001), and improvement in anxiety and depression (P < 0.0001) and QoL (P < 0.0001). CONCLUSIONS: Asian patients with GERD, especially those with NERD, may have lower response rates to PPIs than Western populations. ERD and less severe gastrointestinal symptoms may help to predict symptomatic responses to PPIs in Asian patients. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT00312806.

Characteristics of symptom presentation and risk factors in patients with erosive esophagitis and nonerosive reflux disease.

OBJECTIVE: The aim of this study was to investigate the effect of gender on symptom presentation and quality of life of patients with erosive esophagitis (EE) and nonerosive reflux disorder (NERD). SUBJECTS AND METHODS: Medical records from patients with gastroesophageal reflux disease (GERD) between January and December 2009 were reviewed. The patients were assigned to either the EE or the NERD group. The general demographic data, the modified Chinese GERDQ scores and the Short Form (SF)-36 life quality questionnaire scores of the two groups of patients were compared. RESULTS: Of the 261 patients, 87 (33.3%), 86 (33.0%) and 88 (33.7%) patients were classified into the EE, the NERD and the control groups, respectively. The patients in the EE group were significantly older (48.94 ± 17.38 vs. 43.34 ± 12.67 years), were predominately male (58.6 vs. 39.5%), had more frequently hiatal hernia (34.5 vs 17.4%), had a higher body weight (67.57 ± 15.13 vs. 61.06 ± 11.08 kg) and a higher body mass index (24.09 ± 4.61 vs. 22.68 ± 3.12) than those in the NERD group. The GERD-specific symptom scores and the general life quality scores of the EE and the NERD groups were similar, and both groups had lower life quality scores than the control group did. The female patients with NERD had a higher frequency of GERD symptoms and lower quality of life scores. Gender had no effect on symptom scores or life quality scores in the EE group. CONCLUSION: The GERD-specific symptom severity and general quality of life scores of the EE and the NERD patients were similar. Gender had a great influence on symptom presentation and quality of life in patients with NERD, but not in those with EE.

A miniature ultrasound probe is useful in reducing rebleeding after endoscopic cyanoacrylate injection for hemorrhagic gastric varices.

OBJECTIVE: To better assess the usefulness of miniature ultrasound probe (MUP) sonography in the evaluation of the adequacy of gastric variceal injection with cyanoacrylate to decrease the risk of post injection rebleeding. MATERIAL AND METHODS: Sixty-nine patients with bleeding gastric varices were included in this study. Endoscopic cyanoacrylate injection was performed in the acute phase for variceal hemostasis. After injection, patients (n = 34) included in the MUP group prospectively received endoscopic ultrasonography (EUS) with MUP during each scheduled endoscopic follow-up session. Patients (n = 35) in the control group who were included historically were followed up with the same interval with endoscopy only. RESULTS: Four (11.4%) patients in the control group received reinjection, and there were 10 episodes of rebleeding in 7 (20.0%) patients. Nine (26.5%) patients received reinjection due to inadequate obturation as judged by EUS. There were six episodes of rebleeding in three (8.8%) patients in the MUP group. The free-of-rebleeding rate for the MUP group was significantly higher than that for the control group (p < 0.05). The cumulative survival for the MUP group was slightly better than that for the control group but was not statistically significant. The patients' compliance in both groups was similar. The endosonographers considered the performance of MUP sonography to be convenient. CONCLUSIONS: MUP sonography is useful for the evaluation of the adequacy of tissue adhesive obturation of gastric varices that may reduce the probability of rebleeding.

Diagnosis of Laryngopharyngeal Reflux: Past, Present, and Future-A Mini-Review.

Laryngopharyngeal reflux (LPR) is a variant of gastroesophageal reflux disease (GERD) in which gastric refluxate irritates the lining of the aerodigestive tract and causes troublesome airway symptoms or complications. LPR is a prevalent disease that creates a significant socioeconomic burden due to its negative impact on quality of life, tremendous medical expense, and possible cancer risk. Although treatment modalities are similar between LPR and GERD, the diagnosis of LPR is more challenging than GERD due to its non-specific symptoms/signs. Due to the lack of pathognomonic features of endoscopy, mounting evidence focused on physiological diagnostic testing. Two decades ago, a dual pH probe was considered the gold standard for detecting pharyngeal acidic reflux episodes. Despite an association with LPR, the dual pH was unable to predict the treatment response in clinical practice, presumably due to frequently encountered artifacts. Currently, hypopharygneal multichannel intraluminal impedance-pH catheters incorporating two trans-upper esophageal sphincter impedance sensors enable to differentiate pharyngeal refluxes from swallows. The validation of pharyngeal acid reflux episodes that are relevant to anti-reflux treatment is, therefore, crucial. Given no diagnostic gold standard of LPR, this review article aimed to discuss the evolution of objective diagnostic testing and its predictive role of treatment response.

Impact of Mobile Apps in Conjunction With Percutaneous Endoscopic Gastrostomy on Patients' Complications, Quality of Life, and Health-Related Self-Care Behaviors: Randomized Clinical Trial.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is commonly chosen for long-term enteral nutrition support. However, common complications of PEG include wound infection, leakage, obstruction, bleeding, dislodgement, pneumonia, peritonitis, and more. The anticipation of these complications by both patients and their family caregivers underscores the essential requirement of ongoing technical guidance for the daily care of PEG and the adoption of preventative strategies. OBJECTIVE: This study aimed to establish and compare a health education program utilizing a tracking system for PEG using a mobile app (PEG app) and instant messaging software versus a paper-based health education program with instant messaging software. Their effectiveness in preventing complications, avoiding hospital readmissions, improving self-care practices, and enhancing quality of life outcomes was assessed. METHODS: A randomized controlled trial design was used, and the study sample consisted of patients from a medical center in central Taiwan who underwent thoracic surgery or gastroenterology procedures. Inclusion criteria were being a new case undergoing his or her first gastric tube insertion and having the ability to operate a smartphone. Exclusion criteria were cases requiring tube replacement or nasogastric tubes. A total of 74 participants were enrolled, with 37 participants in the experimental group and 37 participants in the control group. Data collection took place from hospitalization until 1 month after discharge. The experimental group received care using the gastric tube tracking system (PEG app) and the Line app that included phone, text, and photo capture capabilities, while the control group received routine nursing care and used the Line app. RESULTS: The experimental group demonstrated a significant reduction in the occurrence of complications compared with the control group (χ21=12.087, P=.001). Specifically, the occurrence of leakage events was significantly lower in the experimental group than in the control group (χ21=12.906, P=.001). However, the experimental group exhibited superior self-care ability compared with the control group (t72=2.203, P=.03). There was no significant difference in overall quality of life scores between the experimental and control groups (t72=1.603, P=.11). However, the experimental group showed better social aspects of quality of life than the control group (t72=2.164, P=.03). CONCLUSIONS: Integration of the PEG app with instant messaging can enhance self-care ability, improve social aspects of quality of life, and reduce complications. The study results suggest that the PEG app could be used as an adjunct tool to promote patients' self-directed management of their gastric tube at home, particularly for patients who have undergone their first PEG placement and are being discharged from the hospital. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071271; https://tinyurl.com/4vvy584e.

Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH.

Background/Aims: Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. Methods: We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. Results: A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. Conclusion: Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms.

Background/Aims: Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. Methods: In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. Results: Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH- (ILPRS in pH+ vs pH-: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH-: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH- subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH- subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). Conclusion: Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population.

AIM: Currently, atezolizumab combined with bevacizumab is the standard first-line treatment for unresectable hepatocellular carcinoma (HCC), but lenvatinib or sorafenib are still recommended for these patients for some reasons. The aim of the study was to determine the outcomes of Taiwanese patients with advanced-stage HCC who received lenvatinib or sorafenib. METHODS: Data on patients with BCLC stage C HCC who were receiving lenvatinib or sorafenib as the first-line therapy from May 2018 to August 2020 was collected. The individuals with lenvatinib and sorafenib were propensity score-matched at a ratio of 1:2. RESULTS: A total of 22 patients with lenvatinib and 44 patients with sorafenib were enrolled. The ORR (36.4% vs. 11.4%, p = 0.023) and DCR (81.9% vs. 56.9%, p = 0.039) were both higher in the lenvatinib group compared with the sorafenib group. The median overall survival (OS) of the lenvatinib group and the sorafenib group was 9.36 months and 8.36 months, respectively. The best median OS was detected in patients receiving lenvatinib and having an objective tumor response (11.29 months), with a significant difference (p = 0.031) compared with the other groups. CONCLUSION: Lenvatinib, compared to sorafenib, had better ORR and DCR, but similar OS, in Taiwanese patients with advanced-stage HCC. The patients with an objective tumor response had a better OS.

The Combining of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors as First-Line Treatment for Advanced Stage Hepatocellular Carcinoma.

AIM: Hepatocellular carcinoma (HCC) is one of the most common cancers. Tyrosine kinase inhibitors (TKIs), including sorafenib (SOR) and lenvatinib (LEN), as well as immune checkpoint inhibitors (ICIs), including nivolumab (NIVO) and pembrolizumab (PEMBRO), have been approved for the treatment of advanced HCC. The aim of the study is to determine whether advanced-stage HCC patients should receive a combination of TKI and ICI as first-line therapy. METHODS: Data for subjects with BCLC stage C HCC, who were receiving combining TKI and ICI as first-line therapy at Taichung Veterans General Hospital from April 2019 to July 2021, were evaluated. The general and therapeutic outcome data were collected and analyzed. RESULTS: A total of 33 patients were enrolled (8 SOR/NIVO, 4 SOR/PEMBRO, 11 LEN/NIVO, and 10 LEN/PEMBRO). All cases belonged to Child-Pugh class A. The objective response rate was 48.5%, and disease control rate was 72.7%. The average progression-free survival (PFS) and overall survival (OS) of all patients was 9.2 and 17.0 months, respectively. The use of PEMBRO, when compared with NIVO, had a significantly positive impact towards achieving an objective response, defined as either complete response or partial response (OR 5.54, p = 0.045). PFS and OS between the different TKIs or ICIs had no differences. The most adverse event was fatigue (36.4%), and most cases were mild and manageable. CONCLUSION: Combining TKI and ICI provides an acceptable antitumor efficacy in first-line therapy for advanced-stage HCC patients. The survival outcomes between different TKIs or ICIs display no differences.

Clinical values of Barcelona Clinic Liver Cancer subgroup and up-to-7 criteria in intermediate stage hepatocellular carcinoma with transcatheter arterial chemoembolization.

BACKGROUND: Transarterial chemoembolization (TACE) is a recommended treatment for patients with intermediate stage hepatocellular carcinoma (HCC) but with variable treatment outcomes. AIM: To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC. METHODS: Patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. Patients were assigned to either the objective responder (OR) group or the non-OR group according to mRECIST criteria. Clinical and radiological characteristics were compared between the 2 groups. The overall survival of enrolled subjects was analyzed. RESULTS: In 128 enrolled patients, 66 (51.6%) were in the OR group and 62 (48.4%) in the non-OR group. Compared with the non-OR group, the OR group had a significantly smaller HCC size (6.55 cm vs 9.50 cm, P = 0.001) and was within the up-to-7 criteria (50% vs 26.7%, P = 0.001). After multivariable analyses, these significant associations still existed. Overall survival rate of all the subjects averaged 20.65 ± 13.26 mo. The survival rate at 1-year was 64.8%, 2-year was 46.9%, and 3-year was 31.2%. For those patients with OR to TACE, smaller tumor size and within up-to-7 criteria were associated with significantly better overall survival. Those patients with subgroup B1 had the highest OR ratio (75%) and better overall survival (26.70 ± 12.07 mo) after TACE. CONCLUSION: BCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE. BCLC stage B subgroup is useful to predict refractoriness to TACE.

The relationship of salivary and cord blood cortisol in preterm infants.

Recent studies reveal that salivary cortisol measurements accurately reflect blood cortisol levels in older children and adults; yet, the relationship between the two values in premature infants has not been established. This study explores the use of salivary cortisol as an accurate measure of adrenal steroid concentrations in premature infants to provide a reliable and less invasive tool for investigating hormonal stress response. Premature infants (n=51) were recruited, with saliva and blood collected immediately after birth, and cortisol levels measured by radioimmunoassay. A linear relationship emerged between cord plasma and salivary cortisol values in the 102 paired samples [(salivary cortisol) = 0.546 +/- 0.192 x (plasma cortisol), r = 0.481 and p = 0.0003]. Findings demonstrated that salivary and plasma cortisol levels were correlated in premature infants. This information will be useful in future studies that assess use of salivary cortisol to evaluate neonatal stress axis function.

Therapeutic benefits of combined sorafenib for intermediate hepatocellular carcinoma unresponsive to transarterial chemoembolization in a Chinese population.

OBJECTIVE: Transarterial chemoembolization (TACE) is the treatment modality for intermediate, or Barcelona Clinic Liver Cancer stage B, hepatocellular carcinoma (HCC), but its beneficial effect on outcomes is still unsatisfactory. This study aimed to assess the outcomes of combined TACE and sorafenib for patients with intermediate HCC. METHODS: Patients with intermediate HCC who were receiving TACE alone (the monotherapy group), or combined TACE and sorafenib (the combined therapy group) from January 2013 to June 2018 were enrolled. RESULTS: Altogether 64 patients were enrolled, of whom 34 were assigned to the monotherapy group and 30 to the combined therapy group. A prolonged time-to-progression (TTP) (mean 14.46 mo vs 6.39 mo, P = 0.001) was noted in the combined therapy group compared with the monotherapy group. Overall survival (OS) (mean 18.96 mo vs15.44 mo, P = 1.000) between the two groups did not differ significantly. After adjustment, there were no significant differences in the 12-18 month mortality rate between the two groups. CONCLUSION: Patients with intermediate HCC receiving combined TACE and sorafenib had a better TTP, but not OS, than those receiving TACE alone.

Increasing prevalence of erosive esophagitis among Taiwanese aged 40 years and above: a comparison between two time periods.

BACKGROUND: Earlier prevalence studies have reported an increasing trend of gastroesophageal reflux disease in Asia, and obesity may be the promoting factor. GOALS: This study compared the prevalence of erosive esophagitis and obesity status among the same source of subjects in Taiwan between 1995 and 2002. STUDY: In the same routine health checkup unit, we recruited 1902 apparently healthy adults in 2002 matched by sex and age with 2044 individuals recruited in 1995. The prevalence of esophagitis and body mass index between these 2 groups were compared. RESULTS: The crude prevalence of esophagitis increased from 5% in 1995 to 12.6% in 2002 (P<0.0001). Comparing by age stratum, there was an increase of esophagitis among subjects aged 40 years and above, with a dose-response relationship of adjusted prevalence ratios 2.65 [95% confidence interval (CI): 1.10, 4.20] in those aged 40 to 49 years, 3.15 (95% CI: 1.51, 4.79) in those aged 50 to 59 years, and 4.33 (95% CI: 2.56, 6.11) in those aged 60 years and above. The prevalence of esophagitis increased in both sexes. BMI was positively associated with the presence of esophagitis in women, but the proportion of overweight or obesity did not increase in women aged 40 years and above over time. CONCLUSIONS: There was a 2.5-fold of increase in prevalence of erosive esophagitis among Taiwanese adults from 1995 to 2002, particularly in those aged 40 years and above. Factors other than obesity seem to contribute to the increasing trend of erosive esophagitis in Taiwanese women.

Association of heartburn and laryngopharyngeal symptoms with endoscopic reflux esophagitis, smoking, and drinking.

OBJECTIVES: This study was conducted to investigate the association of laryngopharyngeal symptoms and heartburn with endoscopic esophagitis, smoking, and drinking. The clinical importance of the Reflux Symptom Index (RSI) in predicting endoscopic esophagitis was also evaluated. STUDY DESIGN: Case series with planned data collection. SUBJECTS AND METHODS: From November 2006 to February 2007, 156 adults received a whole-body physical check-up. They filled out the RSI questionnaire and were dichotomized into either a "no problem group" or a "possible patients group" according to their scores on the RSI. All subjects received an esophagoscopy. The relationship between RSI score and endoscopic esophagitis, smoking, and drinking was analyzed. RESULTS: Voice change, but not heartburn, was significantly associated with endoscopic reflux esophagitis. Based on the RSI scores, some items in addition to voice change were significantly associated with smoking or drinking but not with endoscopic esophagitis. CONCLUSIONS: While screening patients for reflux esophagitis by using the RSI questionnaire, there is little value in using heartburn to predict endoscopic esophagitis in Taiwanese people. On the other hand, a husky voice might be a good clinical indicator of patients at risk of having reflux esophagitis.

Saliva Pepsin Detection and Proton Pump Inhibitor Response in Suspected Laryngopharyngeal Reflux.

OBJECTIVES/HYPOTHESIS: To evaluate the prediction value of saliva pepsin detection for an 8-week proton pump inhibitor (PPI) response in patients with a Reflux Symptoms Index (RSI) score ≥13, which indicates possible laryngopharyngeal reflux. STUDY DESIGN: Prospective individual single-cohort study. METHODS: Patients were recruited who had experienced chronic laryngopharyngeal symptoms (RSI score ≥13) for more than 3 months after excluding other etiologies. The patients received PPI (40 mg of esomeprazole once daily) treatment for 8 weeks. Prior to treatment, the patients submitted saliva/sputum samples that were collected during the time symptoms were observed. The samples were taken for pepsin detection, and performed using the commercially available Peptest lateral flow device. The association of the Peptest results and PPI response were statistically analyzed with the χ2 test. RESULTS: Seventy-four patients completed the study, and upon completion of PPI treatment, the mean RSI score was significantly reduced from 19.22 ± 5.18 to 8.99 ± 5.69. Forty-four (59.5%) patients exhibited a good response as defined by an RSI score reduction ≥50%. The results of the Peptest were semiquantitatively graded as 0, 1, 2, 3 (negative, weak positive, moderate positive and strong positive, respectively) based upon the visual intensity of the test sample line as compared to the control line. Twenty-four patients (32.4%) exhibited grade 3 strong positive results. The Peptest strong positive results (P < .05) were significantly associated with a good PPI response, with the positive predictive value being 79.2%. CONCLUSIONS: Analysis of strong positive results for pepsin detection in saliva/sputum samples may be a useful, noninvasive method for predicting better PPI response in patients with suspected reflux induced chronic laryngopharyngeal symptoms. LEVEL OF EVIDENCE: 2 Laryngoscope, 129:709-714, 2019.

Benefits of the Seattle biopsy protocol in the diagnosis of Barrett's esophagus in a Chinese population.

AIM: To investigate the benefits of the Seattle protocol in the diagnosis of Chinese individuals with Barrett's esophagus. METHODS: Subjects enrolled were patients from one center with endoscopically-suspected esophageal metaplasia. These patients first received narrow-band imaging-targeted biopsy, and later, the Seattle protocol-guided biopsy, within a period from October 2012 to December 2014. Those cases without initial pathologic patterns of intestinal metaplasia (IM) and then appearance or loss of IM tissue were designated as Group A or B, respectively. Those with initial pathologic patterns of IM, which then persisted or were lost were designated as Group C or D, respectively. RESULTS: The number of cases for each group was as follows: A: 20, B: 78, C: 31 and D: 14. The distribution of the Prague criteria M levels of Group A was significantly higher than Group B (P = 0.174). Among these groups, Group C had the highest proportions of hiatus hernia (54.8%), long segment Barrett's esophagus (29%), and also the highest Prague criteria M levels. The sensitivity of IM detection was 69.2% for the narrow-band imaging-targeted biopsy and 78.5% for the Seattle protocol-guided biopsy. The difference was not significant (P = 0.231). The number of detectable dysplasias increased from one case via the NBI-target biopsy to five cases via the Seattle protocol-guided biopsy, including one case of adenocarcinoma. CONCLUSION: The Seattle protocol improved the IM detection in our subjects with higher Prague criteria M levels and disclosed more cases with dysplastic tissues.