Takahiro Zenda

Roles of the AGE-RAGE system in vascular injury in diabetes

Abstract: This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE‐exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE‐RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Detection of diaphragmatic defect as the cause of severe hepatic hydrothorax with magnetic resonance imaging

Severe right-sided hepatic hydrothorax occurred in an 83-yr-old Japanese woman with a 7-yr history of cryptogenic liver cirrhosis. Transdiaphragmatic communication was indirectly suggested by rapid migration of dye (indocyanine green) from the peritoneal to the pleural space. Magnetic resonance imaging studies also demonstrated a diaphragmatic defect as a characteristic hypointense jet flow across the diaphragm on both T1- and T2-weighted sagittal scans. Although no firm treatment for hepatic hydrothorax has been established and direct demonstration of diaphragmatic defect with noninvasive imaging is extremely rare, testing for diaphragmatic integrity is meaningful to provide a radical or less invasive treatment. Magnetic resonance imaging, as well as color Doppler ultrasonography, may be useful for the detection of diaphragmatic defects as the cause of hepatic hydrothorax.

Small Follicular Lymphoma Arising Near the Ampulla of Vater

A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas.

Primary minute invasive de novo colonic adenocarcinoma appearing as submucosal tumor

A 4 mm white-yellow submucosal tumor-like lesion was detected in the sigmoid colon of an asymptomatic 52-yr-old Japanese man. Because the lesion was unexpectedly suspicious for adenocarcinoma by pathological examination of the biopsy specimen, it was treated by endoscopic mucosal resection. The specimen obtained demonstrated well-differentiated adenocarcinoma without any adenomatous element, and was located principally in the submucosal layer with a maximum depth of 1600 µm from the muscularis mucosae. The cancer exposed to the luminal surface was pathologically concluded to be diminutive. Intriguingly, aggregation of lymphocytes was found beneath the mucosal layer, which might have compromised the integrity of the muscularis mucosae. Because of deep submucosal infiltration and the latent aggressive nature of de novo cancer, the patient underwent an additional partial sigmoidcolectomy, which demonstrated no residual cancer and no regional lymph node metastasis. The lesion in this patient exhibited a previously undescribed appearance of de novo colon cancer as submucosal tumor in an early phase of growth.

Acute peri-myocarditis with an unusual initial manifestation of gallbladder edema and a profound eosinophilic surge during convalescence

A 29-year-old man with fever and right upper quadrant pain was referred to our hospital. Ultrasonography revealed intense gallbladder edema and pericardial effusion. Despite no symptoms and signs related to heart failure, the patient was clinically suspected of cardiac dysfunction related to acute peri-myocarditis based on his symptoms of preceding fever and headache, pericardial effusion, positive troponin T value, elevated B-type natriuretic peptide level, and sequential changes on electrocardiography. With a profound eosinophilic surge (8,022/µL) during convalescence, acute peri-myocarditis and gallbladder edema resolved spontaneously. This case instructively shows that acute peri-myocarditis initially manifests with abdominal symptoms, mimicking acute acalculous cholecystitis. In addition, an extensive review of acute myocarditis cases with peripheral eosinophilia suggests that there is a subgroup characterized by a predilection for young and middle-aged men, concurrence of pericardial effusion, transient eosinophilic surge during convalescence, and favorable outcome.

Follicular lymphoma-related colitis resembling ulcerative colitis

Among the various manifestations of colonic involvement in malignant lymphomas, an ulcerative colitis-like appearance is rare. Herein, we describe a case in which extranodal colonic involvement resembled ulcerative colitis in a patient with advanced follicular lymphoma. A 59-year-old Japanese man with diarrhea and body weight loss was referred to our hospital. Computed tomography (CT) revealed systemic lymphadenopathy, splenomegaly, and thickening of the sigmoid colon and rectum walls. 18F-fluorodeoxy-glucose positron emission tomography (18F-FDG-PET/CT) revealed intense tubular 18F-FDG accumulation extending from the rectum to the colon at the hepatic flexure and much weaker accumulation in the systemic lymph nodes, bone marrow, and spleen. The isotope-enriched areas had an ulcerative colitis-like appearance as shown via colonoscopy. The patient was ultimately diagnosed with follicular lymphoma (stage IV A, grade 1) based on a pathological examination of the neck lymph nodes, iliac bone marrow, and colon. After six courses of chemotherapy (R-CHOP), 18F-FDG-PET/CT confirmed complete remission of the lymphoma including the colonic lesion. This is presumably the first case of ulcerative-like colitis caused by a follicular lymphoma. As a novel approach, the lymphoma-related colitis was detected by comparing the pathology results and the 18F-FDG-PET/CT results.

Acute malignancy-related hydrocephalus uncovered after endoscopic manipulation: possible influence of gastrointestinal endoscopy on concurrent intracranial lesion.

A 78-year-old man underwent biliary stenting by means of endoscopy for obstructive jaundice due to common bile duct cancer. Despite uneventful operation, the patient remained comatose and began to hiccup and vomit with marked gastrointestinal gas retention. Neuroimaging studies disclosed obstructive hydrocephalus caused by a midbrain metastasis, probably from coexisting lung cancer. Ventricular peritoneal shunting restored consciousness and eliminated other gastrointestinal symptoms. This case suggests that gastrointestinal endoscopy may affect concurrent intracranial lesions, resulting in acute distress, presumably by transmission of pressure from the abdomen to a distant body compartment such as the intracranial space, or by endoscopy-related hypoventilation.

Efficacy of Endoscopic Esophageal Variceal Ligation in an Immunocompromised Host

Abstract: We successfully treated esophageal varices by endoscopic variceal ligation (EVL) in a 50‐year‐old female patient with common variable immunodeficiency and liver cirrhosis secondary to hepatitis B. Under the existing disadvantageous conditions including the immunocompromised status, hyperal‐lergic reactions to several drugs, chronic pulmonary infection, and impaired hepatic function, we considered EVL to be of greater potential benefit than endoscopic injection sclerotherapy (EIS). This case highlights the possible merits of EVL over EIS, even in the presence of various restrictions, such as the immunocompromised condition of our patient.