Associations among gastroesophageal reflux disease, psychological stress, and sleep disturbances in Japanese adults.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) and psychological stress are associated with sleep disturbances. The aim of the present study was to examine the prevalence of sleep disturbances, anxiety, and depression by GERD subtypes and to identify factors associated with sleep disturbances in general population. METHODS: A total of 2002 Japanese subjects, who underwent annual health checkups, were enrolled and asked to fill out a questionnaire, including the frequency scale for the symptoms of GERD (FSSG), Athens Insomnia Scale (AIS), Rome III questionnaire, and Hospital Anxiety and Depression Scale (HADS). GERD was divided into asymptomatic erosive reflux disease (a-ERD), symptomatic ERD (s-ERD), and non-erosive reflux disease (NERD), according to the presence or absence of esophageal mucosal injury on endoscopy, and the FSSG scores. Sleep disturbances were diagnosed in subjects with AIS score ≥6. RESULTS: Prevalence of sleep disturbances was significantly higher in GERD subjects than in controls (35.9 and 14.7%, respectively), especially, in the NERD group (45.1%). Sleep duration was significantly shorter in the s-ERD group compared with other groups. Subjects in the NERD and s-ERD groups showed higher HADS scores, resulting in higher incidences of anxiety and depression than those in the control and a-ERD groups. Reflux symptoms, anxiety, depression, and coexisting functional dyspepsia, but not the presence of esophageal mucosal injury, were associated with an increased odds ratio for sleep disturbances. CONCLUSION: There were significant positive associations among reflux symptoms, psychological stress, and sleep disturbance in Japanese adults. Further studies investigating the efficacy of therapy are needed.

Factors Associated with Potassium-Competitive Acid Blocker Non-Response in Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Approximately 20-40% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid-inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), is significantly greater when compared to the effect of PPIs. We investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and factors associated with P-CAB non-response. METHODS: We enrolled 277 GERD patients receiving continuous PPI therapy. Subjects completed a self-report questionnaire including the frequency scale for the symptoms of GERD (FSSG). Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8 weeks. After that, subjects completed the same questionnaire, and the results were used to identify P-CAB responders and non-responders. RESULTS: Twenty-eight patients were identified as P-CAB responders and 26 were non-responders. Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom, and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR 4.34) was associated with P-CAB non-response, whereas alcohol consumption was inversely associated. CONCLUSIONS: Vonoprazan treatment might be appropriate as a promising new strategy for PPI-refractory GERD. Co-existing FD, sleep disturbances, and alcohol abstinence were significantly associated with P-CAB non-response. Other therapeutic options should be considered in patients with these factors.

Heartburn, Functional Dyspepsia, Anxiety/Depression, and Sleep Disturbances Are Associated With Clinically Significant Belching.

BACKGROUND/AIMS: Belching is the act of expelling gas from the stomach or esophagus noisily through the oral cavity. Although it is a physiological phenomenon, belching may also be a symptom of upper gastrointestinal diseases such as reflux esophagitis and functional dyspepsia (FD). A detailed epidemiology of belching has not yet been reported. The aim of this study is to examine the prevalence and clinical characteristics of clinically significant belching (CSB) in adults. METHODS: We analyzed 1998 subjects who visited the hospital for annual health checkups. Belching was evaluated by a simple question "Do you burp a lot?" and scored as 0 (never), 1 (occasionally), 2 (sometimes), 3 (often), or 4 (always). Subjects with CSB were defined as having scores ≥ 3. We also collected the clinical parameters, endoscopic findings, and data according to the Athens Insomnia Scale, Rome IV questionnaire, and Hospital Anxiety and Depression Scale (HADS). RESULTS: Of the 1998 subjects, 121 (6.1%) had CSB. Subjects with CSB had FD more commonly than reflux esophagitis, but presence of heartburn was high (10.7% vs 3.1%). In addition, the HADS and Athens Insomnia Scale scores in subjects with CSB were significantly higher than those in subjects without CSB. Presence of heartburn (OR, 2.07; 95% CI, 1.05-4.09), presence of FD (OR, 2.12; 95% CI, 1.33-3.36), anxiety/depression (OR, 2.29; 95% CI 1.51-3.45), and sleep disturbances (OR, 1.73; 95% CI, 1.14-2.61) were significantly associated with CSB. CONCLUSION: The detailed epidemiology of belching in the general adult population was clarified.

Additional surgical resection after endoscopic mucosal dissection for early gastric cancer: A medium-sized hospital's experience.

PURPOSE: In Japan, the majority of early gastric cancers (EGCs) are now treated with endoscopic submucosal dissection (ESD). Patients with non-curative lesions treated by ESD are advised to undergo additional surgical resection (ASR) based on guidelines from the Japan Gastroenterological Endoscopy Society (JGES) and Japanese Gastric Cancer Association (JGCA). However, many studies have demonstrated that residual cancer and lymph node metastasis are only rarely found in ASR specimens. Here we retrospectively analyzed the conditions that could enable the avoidance of unnecessary ASR. METHODS: The ESD data for 114 absolute indication lesions and 26 lesions of expanded indication lesions were analyzed. The indications and the curability were evaluated according to the JGES/JGCA guidelines. RESULTS: The rates of non-curative resection and ASR were significantly higher in the expanded indication group compared to the absolute indication group (26.9% and 19.2% vs. 7.9% and 0.9%, respectively). ASR was performed for six patients. Three of their ARS specimens contained neither residual cancer nor lymph node metastasis, and the pathological findings of the preceding ESD specimens deviated slightly from the curative criteria defined by the guidelines. The conditions of the lesions that did not meet the curative criteria were as follows: (1) sm1 invasion of undifferentiated-type lesion <10 mm dia., (2) 21-25 mm dia. mucosal undifferentiated-type lesion, or (3) peacemeal resection with a horizontal margin positive for the mucosal differentiated-type. CONCLUSIONS: These data suggest that a close follow-up without ASR might be appropriate for patients in the above-mentioned three categories after non-curative ESD for EGC.

Natural history of major complications in hepatitis C virus-related cirrhosis evaluated by per-rectal portal scintigraphy.

AIM: To examine the correlation between the porto-systemic hypertension evaluated by portal shunt index (PSI) and life-threatening complications, including hepatocellular carcinoma (HCC), liver failure (Child-Pugh stage progression), and esophagogastric varices. METHODS: Two hundred and twelve consecutive subjects with HCV-related cirrhosis (LC-C) underwent per-rectal portal scintigraphy. They were allocated into three groups according to their PSI: group I, PSI< or =10%; group II, 10%

Natural course of changes in hepatic functional reserve in patients with chronic liver diseases evaluated by scintigraphy with GSA.

Hepatic functional reserve can be evaluated in a noninvasive way by scintigraphy with 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA). We monitored hepatic functional reserve in patients with chronic hepatitis and cirrhosis using scintigraphy with 99mTc-GSA to determine the natural course of changes in their hepatic functional reserve. Computer acquisition of gamma-camera data was started before the injection of 185 MBq of 99mTc-GSA and was stopped 20 min later. Time-activity curves were generated from ROI for the heart and liver. A receptor index and index of blood clearance were calculated from radioactivity in the heart and liver. Scintigraphy with 99mTc-GSA was performed in 12 healthy subjects, 86 patients with chronic hepatitis, and 226 patients with cirrhosis. Seventy-two patients (23 with chronic hepatitis, 32 with cirrhosis in Child-Pugh stage A, 15 in stage B, and 2 in stage C) were examined at least twice with 12-72 months intervening. The receptor index was lower for more severe disorders, decreasing in the order of chronic hepatitis and cirrhosis in stages A, B, and C. The index of blood clearance was higher for more severe disorders, increasing in the order of chronic hepatitis and cirrhosis in stages A, B, and C. The mean annual change in the receptor index with chronic hepatitis was -0.0007, that with cirrhosis in stage A was -0.0023, and that with cirrhosis in stage B or C was -0.0117. The difference between the median annual change with cirrhosis in stage B or C and that with chronic hepatitis or cirrhosis in stage A was not significant (P=0.064 and 0.251, respectively). The mean annual change in the index of blood clearance with chronic hepatitis was 0.0018, that with cirrhosis in stage A was 0.0060, and that with cirrhosis in stage B or C was 0.0330. The difference between the median annual change in the index of blood clearance with cirrhosis in stage B or C and that with chronic hepatitis or cirrhosis in stage A was significant (P=0.004 and 0.007, respectively). Hepatic receptor imaging with 99mTc-GSA could be used to noninvasively evaluate the hepatic reserve of various liver diseases. Changes in hepatic functional reserve were not steady; it decreased gradually as disease advanced from chronic hepatitis to cirrhosis in Child-Pugh stage A, and decrease rapidly after development of stage B cirrhosis.

Usefulness of scintigraphy with technetium-99m galactosyl human serum albumin in prediction of prognosis of primary biliary cirrhosis.

Prediction of survival of patients with primary biliary cirrhosis (PBC) has been based on results of blood tests and other indices of clinical condition, which may be affected by treatment. We earlier evaluated hepatic receptor imaging with 99mTc galactosyl human serum albumin as an alternative method for prediction of survival. To evaluate whether this method is useful for this purpose, we examined the cumulative survival rate of patients with PBC since their first examination by this method. The subjects were 60 patients with PBC, 10 healthy subjects, 65 patients with chronic hepatitis, and 196 patients with cirrhosis. Computer acquisition of gamma-camera data was started just before the injection of 99mTc galactosyl human serum albumin and was stopped 20 min later. As indices of hepatic functional reserve, the receptor index and the index of blood clearance were calculated. Among the patients with PBC, the receptor index was lower in those with stage IV than in those with stages I, II, or III, and the index of blood clearance was higher in patients with stage IV than in those with stages I, II, or III. On the basis of the receptor index, the patients with PBC were divided arbitrarily into two groups of roughly equal size: group A with a receptor index of greater-than-or-equal0.94, and group B with index <0.94. On the basis of the index of blood clearance, the patients were also divided into two groups of roughly equal size: group C with an index of blood clearance of <0.52, and group D with index greater-than-or-equal0.52. Cumulative survival rates were significantly lower in group B than in group A (P=0.026), and lower in group D than in group C (P=0.005). Regression analysis showed the index of blood clearance to be significantly related to survival. In conclusion, hepatic receptor imaging with 99mTc galactosyl human serum albumin can be used to noninvasively evaluate the hepatic functional reserve of patients with PBC and is useful clinically in establishing their prognosis.

Relationship between branched-chain amino acid to tyrosine ratio (BTR) and porto-systemic shunt in the Child-Pugh grade A cirrhosis determined by per-rectal portal scintigraphy.

We examined the difference between early cirrhotic patients with lower branched-chain amino acids (BCAA) to tyrosine ratio (BTR) (<4) and higher BTR (>4) in portal circulation using per-rectal portal scintigraphy with technetium-99m pertechnetate. Forty patients with Child-Pugh grade A cirrhosis and serum albumin level between 3.5 and 3.9 g/dl were enrolled in this study. Sixteen patients were infected with HBV and 24 with HCV. Thirteen patients had BTR<4.0 and 27 had BTR>4.0. Shunt index (SI) obtained through per-rectal portal scintigraphy was significantly correlated with BTR (r=-0.558, P<0.0002). ICGR-15 was most strongly correlated with BTR among six parameters representing liver reserve capacity. The mean SI of patients with BTR less than 4 (38.4+/-28.0%) was significantly higher than that of patients with BTR greater than 4 (17.3+/-14.3%) (P=0.0388). The mean concentration of serum BCAA did not significantly differ between the two groups, but the mean concentration of serum tyrosine in the patients with BTR<4 was significantly higher than that in the patients with BTR>4 (P=0.0081). These results suggested that the increase in porto-systemic shunt caused tyrosine passing through liver and stagnating in the serum, as a result of which BTR fall in early cirrhosis. In conclusion, decrease of blood flow through liver and increase in porto-systemic shunt might be partly responsible for deterioration of BTR in early cirrhosis.

Usefulness of per-rectal portal scintigraphy with technetium-99m pertechnetate for prognosis of primary biliary cirrhosis.

BACKGROUND/AIMS: Conventional methods predicting survival in patients with primary biliary cirrhosis are based on the results of blood tests and on clinical condition, both of which may be affected by treatment. Portal circulation can be evaluated in a relatively noninvasive manner by per-rectal portal scintigraphy. We used this method to evaluate portal hemodynamics and assess prognosis in patients with primary biliary cirrhosis. METHODOLOGY: Per-rectal portal scintigraphy with Tc-99m pertechnetate was done in 51 patients with primary biliary cirrhosis. A solution containing Tc-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was calculated from the curves. RESULTS: The shunt index was higher in patients with stage IV primary biliary cirrhosis than in those with stage I, II, or III primary biliary cirrhosis. On the basis of portal shunt index, the patients were divided into those with a shunt index of less than 18%, and those with a shunt index of 18% or more. The cumulative survival rate was lower among patients with the higher shunt index. On regression analysis, the portal shunt index was found to be significantly related to survival. CONCLUSIONS: Our results indicate that per-rectal portal scintigraphy with Tc-99m pertechnetate can be used to non-invasively evaluate the portal circulation of patients with primary biliary cirrhosis and is useful in establishing prognosis in such patients.

Evaluation of ammonia metabolism in the skeletal muscles of patients with cirrhosis using N-13 ammonia PET.

OBJECTIVE: Skeletal muscle is said to compensate for the decreased ammonia metabolism in patients with cirrhosis. Branched-chain amino acids (BCAA) are being used as a treatment for hyperammonemia, and are believed to decrease blood ammonia by consumption of BCAA in skeletal muscles. We examined ammonia metabolism of the skeletal muscles in patients with liver cirrhosis after administration of BCAA using 13N-ammonia positron emission tomography (PET). METHODS: The subjects were patients with compensated or decompensated liver cirrhosis. PET studies were performed before and 2 hours after injection of BCAA. Serial dynamic PET scans (2 min x 10 frames) were started simultaneously with 13N-ammonia injection. The standardized uptake value (SUV) of both thighs was calculated. RESULTS: In the patient with compensated liver cirrhosis, there was little difference in the rate of increase in SUV before to after administration of BCAA. However, in the patient with decompensated liver cirrhosis, the rate of increase in SUV after administration was higher than that before administration of BCAA. CONCLUSION: Ammonia metabolism in the muscle of patients with liver cirrhosis could be examined noninvasively under physiological conditions using 13N-ammonia PET. The muscles were found to metabolize ammonia partially, and the role of this contribution to metabolism of ammonia in patients with decompensated liver cirrhosis is particularly important.

Gastric emptying in patients with chronic liver diseases.

UNLABELLED: There have been a number of reports of gastric emptying in cirrhosis, all with unconfirmed results. Moreover, the mechanism for delayed emptying in cirrhotic patients is unclear. We evaluated gastric emptying in patients with chronic hepatitis and cirrhosis by means of gastric emptying scintigraphy. METHODS: The subjects were 18 normal controls and 75 patients with chronic viral hepatitis (50 patients had chronic hepatitis and 25 patients had cirrhosis). Tc-99m diethyltriamine pentaacetic acid labeled solid meals were used to evaluate gastric emptying; the half-time (T 1/2) of which was calculated. Digestive symptom scores were determined at the time of gastric emptying tests. RESULTS: Fourteen (28%) of 50 patients with chronic hepatitis and 16 (64%) of 25 patients with cirrhosis had delayed gastric emptying. T 1/2 in patients with cirrhosis was significantly higher than that in normal controls and patients with chronic hepatitis (p = 0.0001 and 0.0003, respectively). The difference between T 1/2 in patients with chronic hepatitis and that in normal controls was not significant. On regression analysis, two indices-the serum albumin level and platelet count-were found to be significantly related to delayed gastric emptying. CONCLUSIONS: Gastric emptying was more delayed in cirrhotic patients than in those with chronic hepatitis and normal controls. Delayed gastric emptying may be related to liver function and portal hypertension.

A case of gastric duplication evaluated by gastric emptying scintigraphy.

Gastric duplications are relatively rare, and communication with the gastric lumen is extremely rare. A 67-year-old man was referred to our hospital because of recurrence of epigastric pain and fullness. An upper gastrointestinal contrast study revealed a double compartment stomach, with gastric duplication starting at the esophagogastric junction outside the greater curvature. Computed tomography of the stomach with gastrografin as contrast demonstrated complete communication of the gastric duplication and primary stomach. The patient was diagnosed with complete gastric duplication. Gastric emptying scintigraphy with Tc-99m diethyltriamine pentaacetic acid was performed. Test meal entered the primary stomach and duplication cyst simultaneously, and radioactivity in the primary stomach decreased linearly and gastric emptying was not delayed. In the duplication cyst, about 70% of the food that entered the cyst once was immediately evacuated from it, but the remaining 30% remained in the cyst for a long time. Gastric emptying of the primary stomach was not affected by formation of the duplication cyst.

Poor labeling of Tc-99m red blood cells in vivo in a radionuclide intestinal bleeding study of a patient who had recently undergone frequent blood transfusions.

The authors report poor labeling of Tc-99m red blood cells (RBCs) in vivo in a radionuclide intestinal bleeding study of a patient who had recently undergone frequent blood transfusions. The existence of RBC antibodies, as a result of the recent blood transfusions in this patient, was one of the causes of the poor labeling. In radionuclide bleeding studies with patients with recent blood transfusion, Tc-99m HSA-D must be chosen instead of Tc-99m RBCs in vivo.