A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett's esophagus-related superficial neoplasia.

BACKGROUND: We previously developed a Japan Esophageal Society Barrett's Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. METHODS: We used data from our previous study, including 10 reviewers' assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers' assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

BACKGROUND: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms. METHODS: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. RESULTS: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. CONCLUSION: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.

Newly developed magnifying endoscopic classification of the Japan Esophageal Society to identify superficial Barrett's esophagus-related neoplasms.

AIM AND METHODS: The Japan Esophageal Society created a working committee group consisting of 11 expert endoscopists and 2 pathologists with expertise in Barrett's esophagus (BE) and esophageal adenocarcinoma. The group developed a consensus-based classification for the diagnosis of superficial BE-related neoplasms using magnifying endoscopy. RESULTS: The classification has three characteristics: simplified, an easily understood classification by incorporating the diagnostic criteria for the early gastric cancer, including the white zone and demarcation line, and the presence of a modified flat pattern corresponding to non-dysplastic histology by adding novel diagnostic criteria. Magnifying endoscopic findings are composed of mucosal and vascular patterns, and are initially classified as "visible" or "invisible." Morphologic features were evaluated for "visible" patterns, and were subsequently rated as "regular" or "irregular," and the histology, non-dysplastic or dysplastic, was predicted. CONCLUSION: We introduce the process and outline of the magnifying endoscopic classification.

[Barrett's esophagus: its diagnosis and management in Japan].

The incidence of adenocarcinoma derived from Barrett's esophagus has been steadily increasing during the past some decades in Western countries. The development of better diagnostic and therapeutic strategies for Barrett's esophagus and Barrett's adenocarcinoma have become an important objective. In Japan, Barrett's adenocarcinoma has been gradually increasing as the results of a high incidence of reflux esophagitis, a decreasing of Helicobacter pylori infection and an increasing of obesity, etc. Subsequently, in recent, the management of Barrett's esophagus has come to be of interest as well as in the Western countries. Many issues found in the pathophysiology and epidemiology of Barrett's esophagus in Japanese patients are required to be clarified and the Japanese maneuvers regarding the diagnostic procedure and clinical management including the surveillance for patients with Barrett's esophagus should be established as soon as possible.

[A case of AFP-producing gastric cancer responding to the combination of systemic chemotherapy, transcatheter arterial embolization and hepatic infusion chemotherapy].

We report a case of a 64-year-old male with a-fetoprotein(AFP)-producing gastric cancer accompanied by large liver metastases and multiple lymph node metastases. The patient's serum AFP level was 42,307 ng/mL and a biopsy specimen showed AFP-positive tumor cells immunohistochemically. Systemic chemotherapy by tegafur gimeracil oteracil potassium(S-1)and local therapy for the hepatic metastases consisting of transcatheter arterial embolization (TAE)and infusion of epirubicin(EPI)to the hepatic arteries decreased the serum AFP level and reduced the gastric cancer and metastases. Due to the increase of AFP and lymph node metastases, we had to successively change the regimen to paclitaxel(PTX), a combination of cisplatin(CDDP)/irinotecan(CPT-11)and S-1. Continuous systemic chemotherapy in combination with various drugs for gastric cancer treatment followed by TAE and hepatic infusion chemotherapy for hepatic metastases proved effective. The patient survived for 3 years and 2 months.

Prophylactic administration of antibiotics unnecessary following ultrasound-guided biopsy and ablation therapy for liver tumors: Open-labeled randomized prospective study.

AIM: To determine the prophylactic effect of antibiotics administration in the prevention of infection following an ultrasound-guided percutaneous liver biopsy or treatment of liver tumors, we performed an open-labeled randomized prospective study of patients who received prophylactic antibiotics after undergoing those procedures. METHODS: We studied 101 patients, with ultrasound-guided percutaneous aspiration biopsies of the liver performed in 48 to diagnose diffuse liver diseases or liver tumors, while percutaneous ethanol-injection therapy was performed in two patients with malignant liver tumors and percutaneous radiofrequency ablation was performed in 51 patients. An oral administration of levofloxacin at 400 mg/day was given to 50 of the enrolled patients from the morning of the treatment day for three days. Preventive antibiotics were not administered to the remaining 51 patients. Body temperature, peripheral blood leukocyte number, c-reactive protein, alanine aminotransferase, and lactic dehydrogenase were measured daily for three days after treatment. RESULTS: Most parameters changed following percutaneous treatments of liver tumors, though no significant differences were seen between the patients treated with antibiotics and those untreated. Most significantly, there was no difference in the frequency of post-procedure infection between the groups. CONCLUSION: Our results suggest that prophylactic administration of antibiotics following a percutaneous liver biopsy and treatment of liver tumors does not have a significant impact on the post-procedure results or incidence of infection.

Esophageal epithelial surface in patients with gastroesophageal reflux disease: an electron microscopic study.

AIM: To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD). METHODS: Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease (NERD), and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment. RESULTS: The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals. CONCLUSION: Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.

[Study on the recognition of upper abdominal symptoms by Japanese adults ].

Four hundred and sixty-three cases, who visited medical center for annual check-up, were enrolled in this study. All subjects were required to answer three symptoms in the ten upper abdominal symptoms and the frequency of these symptoms by which they might visit hospital to take medical care. Upper abdominal pain, nausea and chest pain were best three symptoms, which might cause hospital visit and only a few subjects thought that they make a hospital visit by heartburn, acid regurgitation and early satiety. More than 30% of subjects think that they might visit medical center for medical care when these symptoms occur over three times per week. In contrast, upper abdominal pain, nausea, vomiting, heartburn and early satiety were frequently observed in 100 patients, who visited medical center to take medical care. In addition, about half of patients visited medical center when these symptoms occurred every day.

Five-year follow-up study of patients with reflux symptoms and reflux esophagitis in annual medical check-up field.

AIM: To clarify changes in the prevalence of reflux symptoms and reflux esophagitis over a period of 5 years. SUBJECTS AND METHODS: Five hundred thirty-nine study subjects (male: 408, mean age 47.3 years) were assessed using a reflux symptom questionnaire and endoscopic examinations conducted twice, 5 years apart. RESULTS: At enrollment, 88 patients had reflux symptoms and 44 had reflux esophagitis (RE). After 5 years, 58 and 53 patients were diagnosed as having reflux symptoms and RE, respectively. Only 26% of the patients with reflux symptoms at enrollment had the symptoms after 5 years. The presence of reflux symptoms and an increase of BMI were significant risk factors for the presence of reflux symptoms after 5 years. CONCLUSION: Reflux symptoms frequently disappear after 5 years. It is difficult to identify individuals who will still have symptoms after 5 years on the basis of clinical characteristics.

Ferucarbotran expands area treated by radiofrequency ablation in rabbit livers.

BACKGROUND AND AIM: Several studies have examined the factors involved with expansion of the coagulation volume following radiofrequency ablation (RFA). Ferucarbotran contains superparamagnetic iron oxide that generates heat in a radiofrequency electric field and may have an effect on the area affected by RFA. We attempted to determine whether ferucarbotran administration expands radiofrequency-ablated volume using a rabbit model. METHODS: A total of 15 male Japanese white rabbits (16 weeks old) were used and divided into three groups of five each. A 1-mL saline solution was given intravenously into a dorsal ear vein in the control group, whereas 1 mL ferucarbotran solution (0.016 mL/kg bodyweight) was given to the common-dose group and 1 mL of a twofold concentrated ferucarbotran solution (0.032 mL/kg bodyweight) was given to the high-dose group. RFA was performed with a cool-tip electrode 4 h after the administration and immediately thereafter the rabbits were killed, and the volume of the ablated area measured using magnetic resonance imaging (MRI). Following the MRI analysis, the rabbit's livers were resected, and the maximum short axis diameter of the ablated area in each was measured. RESULTS: None of the rabbits died during the RFA procedure. The volume of the ablated area estimated on MR images in the ferucarbotran-administered groups was larger than that in the control group. Further, our macroscopic assessment showed that the maximum short axis diameter had a tendency to increase with ferucarbotran administration. CONCLUSION: Ferucarbotran may expand the area treated by RFA.

Study of arteriosclerosis in patients with hiatal hernia and reflux esophagitis.

BACKGROUND AND AIM: It has been reported that the prevalence of hiatal hernia (HH) and reflux esophagitis (RE) increases with age, as does the degree of arteriosclerosis. However, it has not been investigated whether or not arteriosclerosis is correlated with the presence of HH and RE. Therefore, we prospectively investigated the degree of arteriosclerosis in patients with HH and RE compared with subjects without HH and RE. METHODS: We prospectively enrolled 1683 people who visited Shimane Environment and Health Public Corporation for annual medical check-ups. All subjects were investigated by upper gastrointestinal endoscopy for the possible presence of HH and RE. Factors used for assessing cardiovascular risk were sex, age, body mass index (BMI), smoking and drinking habits, serum total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDLC). Arteriosclerosis was investigated by measuring systolic blood pressure, heart-carotid pulse wave velocity (HCPWV), bilateral ankle brachial index (ABI) and heart-ankle PWV (HAPWV). RESULTS: The number of patients with HH and RE was 624 (37.1%) and 143 (8.5%), respectively. The HDLC level of the patients with HH was significantly lower, and the levels of BMI, TG and arteriosclerotic parameters were higher than those of the subjects without HH after adjusting for confounding factors (sex, age and smoking and drinking habits). Cardiovascular and arteriosclerosis parameters except for TG did not differ between the subjects with and without RE. CONCLUSION: Levels of arteriosclerosis parameters in patients with HH were higher than in those without HH. However, the association between arteriosclerosis and presence of RE was not clarified.

Difference in localization of esophageal mucosal breaks among grades of esophagitis.

BACKGROUND: Gastroesophageal reflux occurs mainly during the daytime in patients with Los Angeles grade A esophagitis, but predominantly during the night in patients with grade C and D esophagitis. The purpose of the present paper was to investigate whether this difference in the pattern of gastroesophageal reflux influences the circumferential localization of erosions in the esophageal wall. METHODS: The subjects were 394 consecutive patients diagnosed endoscopically as having reflux esophagitis (grade A, n = 223; B, n = 93; C, n = 53; D, n = 25 cases). Their endoscopic films were reviewed retrospectively to determine the circumferential location of esophageal mucosal breaks, and also the prevalence and size of hiatal hernia (HH). RESULTS: The numbers of mucosal breaks analyzed in patients with grade A, B and C esophagitis were 321, 173 and 54, respectively. Patients with grade A and B esophagitis had longitudinal mucosal breaks mainly in the right-anterior wall of the lower esophagus, whereas patients with grade C esophagitis had transverse mucosal breaks mainly in the posterior wall. The prevalence and size of HH was significantly higher and larger, respectively, in patients with grade C or D esophagitis than in those with grade A and B esophagitis. CONCLUSION: The circumferential location of esophageal mucosal breaks differs significantly among different grades of esophagitis.

Kinetics of indocyanine green removal from blood can be used to predict the size of the area removed by radiofrequency ablation of hepatic nodules.

BACKGROUND AND AIM: The size of radiofrequency ablation (RFA) in the liver can be negatively influenced by the surrounding blood flow. The indocyanine green (ICG) test can be used to evaluate the effective blood flow in the liver, and distance from the hilus can affect local blood flow. The aim of this study was to assess whether the ICG test or distance from the hilus could be used to predict the size of the ablated area in liver by RFA treatment of hepatocellular carcinoma (HCC) nodules. METHODS: The RFA measurements of 44 HCC nodules in 39 patients were retrospectively studied. Cases were included if they met the following criteria: (i) no catheter treatment before RFA; (ii) no movement of the RFA device; (iii) strict ablation time; and (iv) only one ablation. In all patients, ICG-R15 testing was done immediately before RFA and the initial therapeutic efficacy was evaluated by dynamic computed tomography scanning 2-5 days after RFA. The correlation between the maximum size of the RFA area and the ICG test results or the distance of the target area from the hilus (site of first portal vein divergence) were analyzed statistically. RESULTS: The ICG-R15 result was significantly correlated with the maximum diameter of the ablated area both in 2 cm-electrode tip length (R2 = 0.35, P = 0.0012), and in 3 cm-tip length (R2 = 0.26, P = 0.0377). Multiple-regression analysis showed that the electrode tip length (P = 0.0010) and ICG-R15 (P = 0.0046) were independent factors that could predict the maximum diameter of the RFA area. CONCLUSION: The results of ICG testing can be used to predict the size of the area that will be ablated at a target liver site before RFA treatment.

Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease.

BACKGROUND AND AIM: The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test. RESULTS: Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux. CONCLUSION: The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.

Comparative study of the speed of acid-suppressing effects of oral administration of cimetidine and famotidine.

BACKGROUND AND AIM: H2 histamine receptor antagonists (H2RAs) are widely used in patients with acid-related diseases, and the onset of antisecretory activity of H2RAs is reported to be faster than that of proton pump inhibitors (PPIs). The aim of this study was to compare the rapidity of onset of antisecretory activity of cimetidine and famotidine when orally administered. METHODS: Fifteen healthy male Japanese volunteers (five H. pylori-positive and 10 H. pylori-negative) participated in a randomized cross-over study. All subjects were examined three times by ambulatory 6-h pH monitoring (from 17:30 to 23:30) with no medication or oral administration of 400 mg of cimetidine or 20 mg of famotidine. Drugs were administered at 19:30 after eating a standard meal, and plasma concentrations were also examined for 4 h periods. RESULTS: The plasma concentration of cimetidine increased rapidly after oral administration, while that of famotidine increased gradually. Intragastric pH was increased and percentage time with pH < 4.0 decreased significantly 2 h after administration of either cimetidine or famotidine. There was no statistically significant difference in acid-suppressing effect between cimetidine and famotidine during the short-term post-administration period. CONCLUSION: Rapidity of antisecretory activity did not differ between oral cimetidine and famotidine administered orally.

Nizatidine and cisapride increase salivary secretion in rats.

Saliva is a neurally induced solution with buffering capacity against acidic solutions. Salivation therefore plays an important role in defending the esophageal mucosa against refluxed gastric acid and is evoked by cholinergic stimulation. Both nizatidine and cisapride are reported to increase acetylcholine concentrations in the postganglionic cholinergic synapses. We performed this study to clarify the effect of administration of nizatidine and cisapride on salivary secretion. Eight-week-old male Sprague-Dawley rats were used for the experiments. Histamine-stimulated gastric acid secretion was measured after intraduodenal administration of nizatidine or famotidine to determine the equipotent acid-suppressing doses. Salivary secretion was then measured for 3 hr after intraduodenal administration of nizatidine (30 mg/kg), famotidine (3 mg/kg), or cisapride (1 mg/kg). Both nizatidine and famotidine dose-dependently inhibited histamine-stimulated gastric acid secretion. Total salivary secretion was significantly increased by nizatidine (P = 0.02) and cisapride (P = 0.02) but not by famotidine (P = 0.50) compared with controls.