Advanced Endoscopy for Benign Esophageal Disease: A Review Focused on Non-Erosive Reflux Disease and Eosinophilic Esophagitis.

Advanced endoscopy (AVE) techniques include image-enhanced endoscopy methods, such as narrow-band imaging (NBI), and types of microscopic endoscopy, such as endocytoscopy. In the esophagus, AVE first showed diagnostic utility in the diagnosis of superficial esophageal cancer and was then applied to inflammatory disease. This review focuses on non-erosive reflux disease (NERD) and eosinophilic esophagitis (EoE), which sometimes show no abnormal findings on standard white light endoscopy alone. Studies have demonstrated that advanced endoscopy, including NBI magnification endoscopy and endocytoscopy, improved the diagnostic performance of white-light endoscopy alone for NERD and EoE. In this review, we explain why advanced endoscopy is needed for the diagnosis of these esophageal inflammatory diseases, summarize the study results, and discuss future perspectives.

Salvage Endoscopic Submucosal Dissection for Local Recurrence of Superficial Esophageal Squamous Cell Cancer after Photodynamic Therapy.

Photodynamic therapy is useful as organ-preservation salvage therapy for residual recurrence of esophageal squamous cell carcinoma after chemoradiation therapy. However, the high residual recurrence rate of photodynamic therapy poses a problem. We herein report a patient who underwent photodynamic therapy for recurrence of superficial esophageal squamous cell carcinoma after chemoradiation therapy. The patient later exhibited another episode of recurrence of superficial esophageal squamous cell carcinoma, and R0 curative resection was obtained with endoscopic submucosal dissection. This suggests that endoscopic submucosal dissection may be an effective treatment option that can achieve R0 resection even for residual superficial cancer after salvage photodynamic therapy.

Whole circumferential endoscopic submucosal dissection of superficial adenocarcinoma in long-segment Barrett's esophagus: A case report.

BACKGROUND: Esophageal adenocarcinoma (EAC) derived from long-segment Barrett's esophagus (LSBE) is extremely rare in Asia. LSBE-related EAC is often difficult to diagnose in the horizontal extent. If the tumor has spread throughout the LSBE, whole circumferential endoscopic submucosal dissection (ESD) should be performed, which is difficult to complete safely. Additionally, whole circumferential ESD can bring refractory postoperative stenosis. We hereby report a case of EAC involving the whole circumference of the LSBE, achieving complete endoscopic removal without complications. CASE SUMMARY: An 85-year-old man with the chief complaint of dysphagia underwent esophagogastroduodenoscopy. We suspected a flat-type cancerous lesion that extended the whole circumference of the LSBE (C 3.5, M 4.0) using narrow-band imaging magnification endoscopy (NBI-M). We achieved circumferential en bloc resection of the lesion safely with special ESD techniques. Histology of the ESD specimens demonstrated that the superficial EAC extended the whole circumference of the LSBE, and papillary or well-differentiated tubular adenocarcinoma was confined in the lamina propria mucosa showing a vertical negative margin. To prevent post-ESD stenosis, we performed endoscopic local injection of steroids, followed by oral administration of steroids. There was no evidence of esophageal refractory stenosis or tumor recurrence 30 mo after ESD. In summary, we experienced a rare case of LSBE-related EAC. The horizontal tumor extent was accurately diagnosed by NBI-M. Additionally, we achieve whole circumferential ESD safely without postoperative refractory stenosis. CONCLUSION: NBI-M, ESD, and steroid therapy enabled the curative resection of superficial full circumferential LSBE-related EAC without refractory postoperative stenosis.

Feasibility and Safety of Transjugular Liver Biopsy for Japanese Patients with Chronic Liver Diseases.

BACKGROUND AND STUDY AIM: Transjugular liver biopsy (TJLB) can be used in patients who are ineligible for percutaneous liver biopsy (PLB) with acute and chronic hepatic disease. This study aimed to evaluate the usefulness and safety of TJLB in patients who were not indicated for PLB. METHODS: Between July 2014 and February 2019, a total of 134 patients underwent liver biopsies at our institution. Among these, PLB was performed in 110 patients and TJLB in 24 patients. A retrospective comparison of clinical results in these patients was then performed. The primary endpoints of this study were the utility and safety of TJLB in patients who were not indicated for PLB. RESULTS: The procedural success rate was 100% in both groups. The clinical response rate and the effective tissue sampling rate were 100% in the TJLB group and 97% in the PLB group (p = 0.55). There was no difference in the number of portal fields examined retrospectively between the two groups. No serious adverse events were observed in either group. CONCLUSIONS: It is suggested that TJLB is useful because it can be safely performed in patients with poor general condition who are not indicated for PLB.

Gastric Dieulafoy's lesion with subepithelial lesion-like morphology.

Most cases of Dieulafoy's lesion, a rare cause of upper gastrointestinal bleeding, occur in the upper gastric corpus, usually with no edematous bulging or fold convergence around the mucosal defect. This report describes a case of Dieulafoy's lesion with subepithelial lesion (SEL)-like morphology. Endoscopic treatment by hemoclipping was difficult. Because of repeated bleeding, abdominal dynamic contrast computed tomography (CT) was conducted. Results showed a large caliber, tortuous artery branching directly from the celiac artery and feeding into the gastric wall of the gastric fundus. Rupture of this vessel in the submucosa was thought to be responsible for the SEL-like morphology. All findings indicated endoscopic treatment from the gastric mucosal side was too difficult. Therefore, we treated the lesion using interventional radiology (IR) technique of vascular embolization. If an SEL-like Dieulafoy's lesion cannot be treated by endoscopic hemostasis, then IR might be necessary to treat the vascular anomaly.

A Case of Lung Abscess Caused by Double Immunosuppressive Therapy to Treat Ulcerative Colitis.

A 25-year-old man was admitted to our institution for remission induction therapy to treat a 12-year condition of ulcerative colitis (UC). Previously, he was treated with drugs, such as mesalamine, immunomodulators, prednisolone (PSL), and anti-TNFα anti-body, but remission was not maintained. Therefore, we started remission induction therapy with 20 mg/day of tofacitinib (TOF) to inhibit the action of Janus kinase. On the 29th day after TOF administration, he developed a lung abscess with high fever. A chronic bulla was already present in his lung; therefore, the lung abscess was likely formed due to a combination of the bulla being present and the pharmacological effects of TOF. Our report is significant as it highlights the compounding association between TOF and PSL therapy and bulla presence with the rare adverse effect of developing an abscess.

Huge Amoebic Liver Abscess in the Left Lobe Treated by Oral Administration of Metronidazole.

A man in his 60s visited a clinic with chief complaints of a fever and general malaise. Suspecting a liver abscess in the left lobe with infiltration into the subcutaneous fat tissue under the rectus abdominis muscle based on computed tomography findings, we performed fine-needle aspiration. An amoebic liver abscess was diagnosed. Remission was achieved by the oral administration of metronidazole alone without placement of a drainage tube. The results obtained in this case suggest that the first line of treatment should be a non-invasive approach with oral administration alone. Invasive intervention should then be considered depending on subsequent progress.

A Case of Bilateral Acute Inferior Limb Ischemia in a Patient With Ulcerative Colitis.

A patient was diagnosed with ulcerative colitis (UC) in 2010. In March 2015, she had abdominal pain, diarrhea, bloody stool, and UC has relapsed. In June 2015, pain and sensory disturbance of both lower limbs appeared. Blood flow at the distal femoral artery was not confirmed with magnetic resonance angiography, and it was diagnosed as bilateral acute inferior limb ischemia. Arterial thrombolectomy with Fogarty's balloon catheter was performed and blood flow was improved. The severity of UC was moderate with Mayo score 8. Thrombosis is considered to be a complication with a high incidence in inflammatory bowel disease. Reports of arterial thrombosis are very rare. It is important to evaluate the risk of bleeding and thrombosis in active or severe cases in UC and need to do thrombotic prophylactic treatment simultaneously with UC treatment.

Safety and Efficacy of Nonanesthesiologist-Administrated Propofol during Endoscopic Submucosal Dissection of Gastric Epithelial Tumors.

OBJECTIVE: There is no consensus regarding administration of propofol for performing endoscopic submucosal dissection (ESD) in patients with comorbidities. The aim of this study was to evaluate the safety and efficacy of propofol-induced sedation administered by nonanesthesiologists during ESD of gastric cancer in patients with comorbidities classified according to the American Society of Anesthesiologists (ASA) physical status. METHODS: Five hundred and twenty-two patients who underwent ESD for gastric epithelial tumors under sedation by nonanesthesiologist-administrated propofol between April 2011 and October 2017 at Dokkyo Medical University Hospital were enrolled in this study. The patients were divided into 3 groups according to the ASA physical status classification. Hypotension, desaturation, and bradycardia were evaluated as the adverse events associated with propofol. The safety of sedation by nonanesthesiologist-administrated propofol was measured as the primary outcome. RESULTS: The patients were classified according to the ASA physical status classification: 182 with no comorbidity (ASA 1), 273 with mild comorbidity (ASA 2), and 67 with severe comorbidity (ASA 3). The median age of the patients with ASA physical status of 2/3 was higher than the median age of those with ASA physical status of 1. There was no significant difference in tumor characteristics, total amount of propofol used, or ESD procedure time, among the 3 groups. Adverse events related to propofol in the 522 patients were as follows: hypotension (systolic blood pressure < 90 mmHg) in 113 patients (21.6%), respiratory depression (SpO2 < 90%) in 265 patients (50.8%), and bradycardia (pulse rate < 50 bpm) in 39 patients (7.47%). There was no significant difference in the incidences of adverse events among the 3 groups during induction, maintenance, or recovery. No severe adverse event was reported. ASA 3 patients had a significantly longer mean length of hospital stay (8 days for ASA 1, 9 days for ASA 2, and 9 days for ASA 3, P = 0.003). However, the difference did not appear to be clinically significant. CONCLUSIONS: Sedation by nonanesthesiologist-administrated propofol during ESD is safe and effective, even for at-risk patients according to the ASA physical status classification.

Retroperitoneal Hematoma: Rupture of Aneurysm in the Arc of Bühler Caused by Median Arcuate Ligament Syndrome.

We herein report a case with aneurysm rupture in the arc of Bühler (AOB) caused by median arcuate ligament syndrome (MALS). The patient experienced a sudden onset of upper abdominal pain. Contrast-enhanced abdominal computed tomography (CT) showed an iso- to hyper-enhancing area mainly ranging from the dorsal aspect of the pancreatic head to the retroperitoneum around the right kidney. Abdominal angiography revealed marked stenosis in the origin of the celiac artery caused by MALS and a 7-mm saccular aneurysm in the AOB. Thus, we diagnosed the pain as having been caused by aneurysm rupture in the AOB due to MALS. The patient's symptoms and anemia also improved to normal range without surgery. Careful follow-up, considering possible recurrence of aneurysm at other sites in the future, is essential.

Complementary and alternative medicine for allergic rhinitis in Japan.

BACKGROUND: Complementary and alternative medicine (CAM) is extensively used in patients with allergic diseases worldwide. The purpose of this study was to investigate the actual situation of CAM practice in the treatment of allergic rhinitis. METHODS: We distributed questionnaires to otolaryngologists at 114 facilities in Japan. The subjects who participated in this study included children <16 years of age and adults ≥16 years of age diagnosed with allergic rhinitis by otolaryngologists. The survey was performed in the period from September 2007 to August 2009. Furthermore, we performed the same investigation out of the hospital setting, such as during general health examinations. All questionnaires were returned to Chiba University and analyzed. RESULTS: The proportions of patients who had ever experimented with CAM in the hospital survey were 7.1% (225/3170) and 19.2% (1416/7363) of children and adults, respectively. Approximately 36.2% of the adult patients thought that the treatments were effective. The main reasons for CAM use were safety, convenience and low price. However, the group who spent more than $1000 on CAM felt more dissatisfaction and anxiety related to treatment at the hospital. The situation of CAM practice was not consistent and was instead influenced by the backgrounds of the subjects. CONCLUSIONS: Many patients who receive CAM report feeling that the effects of treatment provided by hospitals are insufficient and have concerns about the side effects of such treatments. Information regarding standard treatments, as described in the guidelines, should become widely known and diffused, and strong communication with patients should be considered.

Effect of prehydration on nasal mucociliary clearance in low relative humidity.

OBJECTIVE: Nasal mucociliary clearance, which plays an important role in defending the respiratory system, tends to decrease under conditions of low relative humidity (RH). The purpose of this randomized cross-over study was to investigate the preventive effect of prehydration on nasal mucociliary clearance under low RH conditions. METHODS: Fourteen young healthy subjects were assigned to three interventions: prehydration (6ml/kg body weight) using water (W), prehydration using a carbohydrate-electrolyte beverage (CE), and control conditions (Cont) with no prehydration. For each intervention trial, subjects sat for 4h in an environmental chamber (23°C, 10% RH). Nasal mucociliary clearance was measured by the saccharin transit time (ST). Furthermore, a dry sensation of the mucosa, urine volume, and body weight were measured at the baseline, 2h and 4h after entering the environmental chamber, respectively. RESULTS: ST was prolonged under the Cont conditions after entering the environmental chamber. Prehydration with CE led to a significantly lower ST compared to the Cont pretreatment at 2h, whereas the W trial showed no significance difference in comparison to the Cont values. CONCLUSION: These results suggest that prehydration with a carbohydrate-electrolyte beverage is therefore beneficial for maintaining better nasal mucociliary clearance at least for 2h under low RH conditions.

Efficacy of combined treatment with S-carboxymethylcysteine (carbocisteine) and clarithromycin in chronic rhinosinusitis patients without nasal polyp or with small nasal polyp.

OBJECTIVE: In Japan, fourteen-membered ring macrolides, antibacterial agents, and S-carboxymethylcysteine (SCMC; carbocisteine), a mucolytic, are commonly used to treat chronic rhinosinusitis (CRS), and they are also used in combination. However, no large-scale randomized study has examined the effects of these pharmacotherapies. The aim of this study is to evaluate the effect of combined administration of clarithromycin (CAM), a fourteen-membered ring macrolide, and SCMC, compared with CAM single therapy. METHODS: Patients with CRS were centrally registered and randomly assigned to treatment with CAM (200mg/day) alone (monotherapy group) or CAM (200mg/day) in combination with SCMC (1500mg/day; combination group) for 12 weeks. We assessed the clinical efficacy of the treatments using measures of subjective symptoms and objective findings, health-related quality of life (HRQOL) determined by the 20-Item Sino-Nasal Outcome Test (SNOT-20) score and computed tomography (CT) score. RESULTS: Four hundred twenty-five subjects were enrolled (combination group, 213; monotherapy group, 212). At week 12 of treatment, the rate of effectiveness was significantly higher in the combination group (64.2%) compared with the monotherapy group (45.6%; P=0.001). In addition, objective findings, including characteristics of nasal discharge (P=0.008) and post-nasal discharge (P=0.002) were significantly improved in the combination group. In both groups, SNOT-20 and CT scores were significantly improved from week 0 (P<0.001), and were not significantly different between groups. CONCLUSION: The results indicated that long-term combination therapy with SCMC at a dose of 1500mg/day and CAM at a dose of 200mg/day is effective for improving subjective symptoms and objective findings in adult patients with CRS.

Effects of clarithromycin and dexamethasone on mucus production in isografted rat trachea.

OBJECTIVES: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production. METHODS: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined. RESULTS: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 µg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS. CONCLUSIONS: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.

Reliability and validity assessments of a Japanese version of QOL 20-Item Sino-Nasal Outcome Test for chronic rhinosinusitis.

OBJECTIVE: The objective of this study was to assess the reliability and validity of a Japanese version of the 20-Item Sino-Nasal Outcome Test SNOT-20, which is one of the quality-of-life (QOL) evaluation sheets for chronic rhinosinusitis (CRS), and assess its reliability and validity. METHODS: The SNOT-20 was conducted in patients with CRS and in healthy volunteers. The response rate was evaluated as the feasibility of this test, and reliability and internal consistency were assessed as reliability. In addition, concurrent validity and discriminant validity were assessed as validity. RESULTS: Regarding the feasibility of this test, the response rate for each question item in the SNOT-20 was nearly 100% for all 20 items. For reliability, test-retest reliability was r=0.890 and the internal consistency was alpha=0.903. For validity, the concurrent validity was r=0.162 when compared with objective findings in the nasal cavity, and was r=0.431 when compared with the score for general physical condition, which evaluate the patient's general condition. Discriminant validity was significantly higher in patients with CRS than in healthy volunteers (p<0.001). Moreover, when the discriminant validity was assessed using an ROC (receiver operating characteristic) curve, it was found that ROC-AUC (the area under the curve)=0.775. CONCLUSION: The reliability and validity of a Japanese version of the SNOT-20 were assessed in this study. It is thought that the SNOT-20 serves as a useful QOL evaluation sheet for CRS.

Effect of vitamin K2 on the development of hepatocellular carcinoma in type C cirrhosis.

BACKGROUND/AIMS: Hepatocellular carcinoma occurs frequently in cirrhosis related to hepatitis C virus (type C cirrhosis), and preventative treatment with interferon is costly and likely to cause adverse reactions. Menatetrenone, a vitamin K2 preparation, has recently been reported to inhibit the posttreatment relapse of hepatocellular carcinoma. We therefore examined whether menatetrenone could prevent the development of hepatocellular carcinoma in patients with type C cirrhosis. METHODOLOGY: This prospective, randomized trial recruited patients with type C cirrhosis, platelet count of 10 x 10(4) microl or less, and no history of hepatocellular carcinoma. Patients were assigned to a menatetrenone group (n = 22, 4 5mg of menatetrenone daily, orally) or a control group (n = 18). Follow-up with image diagnosis was performed every 3-6 months. RESULTS: No adverse events of menatetrenone treatment were observed. Hepatocellular carcinoma occurred in 2 of 22 patients in the menatetrenone group (9.1%) and 5 of 18 patients in the control group (27.8%); however, this difference did not reach statistical significance. CONCLUSIONS: The present findings suggest that menatetrenone has some inhibitory effect on development of hepatocellular carcinoma in patients with type C cirrhosis. Consequently, to further validate its benefits, we believe that menatetrenone should be actively administered to patients with intractable (interferon-resistant) cirrhosis.

Prostaglandin E2 receptor EP2, EP3, and EP4 agonists inhibit antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats.

OBJECTIVES: Prostaglandin (PG) E2 is a potential anti-inflammatory mediator that attenuates airway inflammation. To elucidate the functions of the PGE2 receptors (EP1, EP2, EP3, and EP4) in allergic inflammation, we examined the in vivo effects of EP agonists on mucus hypersecretion and eosinophil infiltration in rat nasal epithelium. METHODS: We induced hypertrophic and metaplastic changes in goblet cells in nasal epithelium of ovalbumin-sensitized rats by intranasal challenge with ovalbumin. The effects of subcutaneous injections of EP agonists on mucus production and eosinophil infiltration were examined. RESULTS: The EP4 agonist (1 to 100 microg/kg) dose-dependently inhibited ovalbumin-induced mucus production. The EP2 and EP3 agonists (100 microg/kg) also significantly inhibited mucus production. The EP3 agonist inhibited antigen-induced eosinophil infiltration, whereas the EP1 agonist showed no effect. This suppression of mucus production by the EP4 agonist was only effective when the EP4 agonist was given in the effector phase; administration in the induction phase resulted in no effect. CONCLUSIONS: These results indicate that PGE2 acts as an anti-inflammatory mediator via the EP receptors of airways in allergic inflammation. Selective EP agonists may provide a new therapeutic strategy for airway mucus hypersecretion.

Remodeling of nasal mucosa by allergen exposure in guinea pigs is suppressed by steroid and pranlukast.

BACKGROUND: It is unclear whether remodeling exists in allergic rhinitis in man. The aim of this study was to establish a guinea pig model of allergic rhinitis with remodeling and to examine the effects of dexamethasone and pranlukast on nasal mucosa remodeling. METHODS: In the first experiment, three groups of ovalbumin-sensitized Hartley guinea pigs received intranasal challenges with ovalbumin for 1, 8, 12 weeks, respectively. In the second experiment, to examine the effect of dexamethasone and pranlukast, the animals were divided into 4 groups: negative control group; ovalbumin-sensitized group; ovalbumin + dexamethasone group; and ovalbumin + pranlukast group. During 12 weeks of intranasal exposure to ovalbumin, the latter two groups received daily intraperitoneal injections of dexamethasone and pranlukast, respectively. RESULTS: In the first experiment, in contrast to the negative control group, the ovalbumin-sensitized group exhibited significant goblet cell hyperplasia, epithelial damage and deposition of extracellular matrix in the nasal septal mucosa and conchae. In the second experiment, these changes were significantly inhibited by dexamethasone and pranlukast, respectively. CONCLUSIONS: We have established a model of upper airway remodeling in guinea pigs. The tissue remodeling was inhibited by early intervention with the antiallergic-inflammatory agents dexamethasone and pranlukast.

[Clinical analysis of hyposmia-associated taste dysfunction].

We clarified the clinical features of "flavor dysfunction," defined as olfactory dysfunction with self-reported hypogeusia but normal taste function in gustatory tests compared to those of "smell and taste dysfunction" hyposmia and hypogeusia in olfactory and gustatory tests. Patients with flavor dysfunction reported significantly milder taste loss than those with other smell and taste dysfunction. The major smell and taste loss etiology was upper respiratory tract infection (URI) in the flavor dysfunction group and the URI rate was significantly higher in the flavor dysfunction group than in the smell and taste dysfunction group. Smell identification thresholds in T & T olfactometry were not different between groups. Flavor dysfunction, hyposmia was treated medically but not with conventional hypogeusia medication. Medication including zinc was administered for other smell and taste dysfunction. Both groups significantly recovered from taste dysfunction. Our results indicate that treating olfactory dysfunction effectively improves flavor dysfunction but hypogeusia need not necessarily be treated. Hyposmia and hypogeusia must be treated together for other smell and taste dysfunction, making it vital that we conduct appropriate gustatory testing to correctly differentiate between flavor and other smell and taste dysfunctions.

Th2 cytokine inhibitor suplatast tosilate inhibits antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats.

OBJECTIVES: Th2 cytokines such as interleukin (IL) 4 and IL-13 are potential mediators for mucus hypersecretion in allergic inflammation. To elucidate the functions of Th2 cytokines in allergic rhinitis, we examined the in vivo effects of the Th2 cytokine inhibitor suplatast tosilate on mucus hypersecretion and eosinophil infiltration in rat nasal epithelium. METHODS: We induced hypertrophic and metaplastic changes in goblet cells in the nasal epithelium of ovalbumin-sensitized rats by intranasal challenge with ovalbumin. The effects of orally administered suplatast tosilate on mucus production and eosinophil infiltration were examined. RESULTS: Suplatast tosilate (30 and 100 mg/kg) dose-dependently inhibited ovalbumin-induced mucus production and eosinophil infiltration. These suppressions of mucus production and eosinophil infiltration were only effective when suplatast tosilate was given in the effector phase; administration in the induction phase resulted in no effect. CONCLUSIONS: These results indicate that Th2 cytokines are important mediators of mucus hypersecretion and eosinophil infiltration in allergic rhinitis. Suplatast tosilate may be useful for the treatment of allergic rhinitis by attenuating the inflammation of the effector phase.