Kazunao Hayashi

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder (EoGD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis (EoE), subepithelial eosinophilic esophagitis (sEoE) and eosinophilic esophageal myositis (EoEM), identified by endoscopy, manometry and serum immunoglobulin E levels (s-IgE), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples. RESULTS In five patients with EoE, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with sEoE and four with EoEM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with EoE and sEoE with some variation, while EoEM was associated with hypercontractile or hypertensive peristalsis, with elevated s-IgE. Histology revealed the following eosinophils per high-power field values. EoE = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; sEoE = 3 in the epithelium and 35 in the subepithelium (conventional biopsy); EoEM = none in the epithelium, 10.7 ± 11.7 in the subepithelium (conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria (peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to EoE. Eotaxin-3, IL-5 and IL-13 were overexpressed in EoE. CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between EoE, sEoE and EoEM, and reflected a different pathogenesis between these esophageal EoGDs.

The Combination Therapy of Dissolution Using Carbonated Liquid and Endoscopic Procedure for Bezoars: Pragmatical and Clinical Review

Bezoars are relatively rare foreign bodies of gastrointestinal tract and often cause ileus and ulcerative lesions in the stomach and subsequent bleeding and perforation due to their size and stiffness. Therefore, the removal of bezoars is essential and recent development of devices, the endoscopic removal procedure, is often applied. However, due to their stiffness, simple endoscopic removal failed in not a few cases, and surgical removal has also been used. Recently, the efficacy of a combination therapy of endoscopic procedure and dissolution using carbonated liquid has been reported. To develop the safe and effective removal procedure, we carefully reviewed a total of 55 reported cases in this study including our 3 additional cases, successfully treated with dissolution with endoscopic fragmentation. In summary, the data showed the efficiency in the combination therapy, treating the larger size of bezoar and reducing the length of hospital stay. To the best of our knowledge, this is the largest pragmatical and clinical review for the combination therapy of dissolution and endoscopic treatment for bezoars. This review should help physicians to manage bezoars more efficiently.

Giant hepatic cyst with septal structure: diagnosis and management.

The hepatic cyst is a common benign liver tumor, and no surgical treatment is necessary. However, it is difficult to correctly diagnose the giant hepatic cyst containing the solid septal structures inside, from the malignant cystadenocarcinomas. The various imaging modalities such as computed tomography, magnetic resonance imaging, and ultrasonography, have been developed and are useful for the diagnosis of these liver tumors. Reviewing the other reports in this paper, the combination of more than 2 modalities will help to diagnose these tumors; however, the malignant potential is unable to be excluded if the tumor is huge. Therefore, the surgical resection should be considered for the huge hepatic cysts with septal structures if the correct diagnosis is unable to be made. For example, when the hemorrhages cause the granulation in the septa which often shows neovascularization, the imaging modalities are unable to define this situation from the malignant tissue with hypervascularity. Therefore, with the careful review of other reports, we conclude that if the imaging studies show the possible malignant potential or the sizing-up is marked, the surgical treatment should be considered with the consent from the patients.

Full‐layer mucosal histology in achalasia: Histological epithelial wave is characteristic in “pinstripe pattern”‐positive achalasia

Previously, the mucosal histology in achalasia has only been investigated using superficial biopsy or surgically resected esophageal specimens in end‐stage cases. We investigated the histology of the full‐layer mucosa in early and advanced achalasia.

Efficacy and Safety of Pancreas-Targeted Hydrodynamic Gene Delivery in Rats

Development of an effective, safe, and convenient method for gene delivery to the pancreas is a critical step toward gene therapy for pancreatic diseases. Therefore, we tested the possibility of applying the principle of hydrodynamic gene delivery for successful gene transfer to pancreas using rats as a model. The established procedure involves the insertion of a catheter into the superior mesenteric vein with temporary blood flow occlusion at the portal vein and hydrodynamic injection of DNA solution. We demonstrated that our procedure achieved efficient pancreas-specific gene expression that was 2,000-fold higher than that seen in the pancreas after the systemic hydrodynamic gene delivery. In addition, the level of gene expression achieved in the pancreas by the pancreas-specific gene delivery was comparable to the level in the liver achieved by a liver-specific hydrodynamic gene delivery. The optimal level of reporter gene expression in the pancreas requires an injection volume equivalent to 2.0% body weight with flow rate of 1 mL/s and plasmid DNA concentration at 5 μg/mL. With the exception of transient expansion of intercellular spaces and elevation of serum amylase levels, which recovered within 3 days, no permanent tissue damage was observed. These results suggest that pancreas-targeted hydrodynamic gene delivery is an effective and safe method for gene delivery to the pancreas and clinically applicable.

A Mesenteric Desmoid Tumor with Rapid Progression

We herein report the case of a rapidly progressive sporadic mesenteric desmoid tumor (DT). A 62-year-old woman presented with a 4-cm-diameter palpable mass in the left supraumbilical area. The mass showed an ill-defined margin with heterogeneous delayed enhancement on computed tomography and heterogeneous high intensity on T2-weighted magnetic resonance imaging. Sixteen months after the initial observation, the mass had grown in size, reaching 13 cm in diameter. The resected mass was histologically confirmed as a DT of the mesentery. Since DT often has an unpredictable clinical course, clinicians should bear in mind the need for imaging follow-up.

Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 0.01, r = -0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.

Gastrointestinal: A case of hypereosinophilic syndrome with esophageal involvement

A 38-year-old woman was admitted for an investigation into the cause of her dysphagia. Laboratory examination revealed an elevated peripheral eosinophil level (7198/μL, 36.5%). A bone marrow biopsy showed hypercellularity with markedly increased eosinophils, but clonal abnormalities were absent (Fig. 1). Therefore, she was diagnosed with idiopathic hypereosinophilic syndrome (HES). Endoscopy showed no evidence of anatomical lesions or neoplasia, and esophageal mucosa biopsies showed no evidence of eosinophilic infiltration. High-resolution manometry revealed hypercontractions, with a distal contractile integral value of 11 871.7 mmHg/s/cm (Fig. 2a). Endoscopic ultrasound showed a hypo-echoic, thickened esophageal muscle layer with a measured thickness of 4.3 mm (Fig. 2b). Because the peripheral eosinophil levels rapidly increased up to more than 70 000/μL, methylprednisolone pulse therapy was initiated. Thereafter, her symptoms improved, including a prompt decrease in the eosinophil count. High-resolution manometry and endoscopic ultrasound were repeated and revealed normal esophageal peristalsis with a distal contractile integral value of 3929.5 mmHg/s/cm (Fig. 2a, inset) and decreased muscle layer thickening (diameter, 1.5 mm; Fig. 2b, inset). The marked bone marrow eosinophil infiltration and the effectiveness of steroid therapy indicated that her dysphagia was caused by eosinophilic infiltration of the esophageal muscle layer due to HES. According to the World Health Organization classification, the definition of idiopathic HES depends on the following: (i) primary and secondary causes of hypereosinophilia must be excluded, (ii) an absolute eosinophilic count of >1500/mm must persist for at least 6 months, and (iii) organ damage must be present. In patients with HES, dermatologic or pulmonary involvement is relatively common; however, esophageal involvement manifesting with hypercontractions had not previously been reported. We have reported that eosinophilic infiltration of the esophagealmuscular layer without epithelial findings occurs in patients with a Jackhammer

Successful treatment of aortic dissection during sorafenib therapy for hepatocellular carcinoma

Our case highlights the need for caution during vascular endothelial growth factor pathway inhibitor (VPI) therapy and for the occurrence of aortic dissection. If Stanford classification type A aortic dissection occurs during VPI therapy, surgical intervention should be considered to prevent cardiac tamponade if the patients clinical condition permits it.

Endoscopic ultrasound-guided fine-needle aspiration for diagnosing a rare extraluminal duodenal gastrointestinal tumor

Duodenal gastrointestinal stromal tumors (GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.