Yoshiko Soga

Real‐time tissue elastography for evaluation of hepatic fibrosis and portal hypertension in nonalcoholic fatty liver diseases

The aim of this study was to prospectively measure liver stiffness with real‐time tissue elastography in patients with nonalcoholic fatty liver diseases (NAFLD) and to compare the result with the clinical assessment of fibrosis using histological stage. One hundred and eighty‐one prospectively enrolled patients underwent real‐time tissue elastography, with the first 106 being analyzed as the training set and the remaining 75 being evaluated as the validation set. Hepatic and splenic elastic ratios were calculated and compared with stage of histological fibrosis. Portal hypertension (PH) was assessed. Real‐time tissue elastography cut‐off values by stage in the training set were 2.47 for F1, 2.67 for F2, 3.02 for F3, and 3.36 for F4. Using these cut‐off values, the diagnostic accuracy of hepatic fibrosis in the validation set was 82.6%‐96.0% in all stages. Only portal fibrosis correlated with the hepatic elastic ratio by multivariate analysis. The area under the receiver operating characteristic curve of elastic ratio better correlated than serum fibrosis markers in both early and advanced fibrosis stages. Patients with PH, defined by splenic elasticity, had early fibrosis. Patients with severe PH were found only in the group with cirrhosis. Conclusion: Real‐time tissue elastography is useful in evaluating hepatic fibrosis and PH in patients with NAFLD. (HEPATOLOGY 2012)

Expression of sphingosine kinase 2 in synovial fibroblasts of rheumatoid arthritis contributing to apoptosis by a sphingosine analogue, FTY720

Gene expression profiles in synovial tissues from rheumatoid arthritis (RA) patients have yielded useful information on the pathogenetic process of the synovitis. In one group of them, sphingosine kinase 2 (SPHK2), a nuclear protein regulating cell proliferation, seemed to be highly expressed, undergoing a different pathogenetic process of synovitis. In the present study it was clarified that SPHK2 was expressed in the synovial fibroblasts of the synovial tissues obtained from the knee joints of the RA patients. In the cultured synovial fibroblasts from these patients, SPHK2 was more highly expressed than that in the human macrophage cell line, THP‐1 and human dermal fibroblasts. SPHK2 was expressed in and around the nucleus and transferred to the cytoplasm and cell surface by the administration of epidermal growth factor, associated with the increased expression of sphingosine‐1‐phosphate. A sphingosine analogue, FTY720, which is activated by phosphorylation specifically by SPHK2, mediated apoptotic signaling of the cultured synovial fibroblasts. These findings suggest that SPHK2 may regulate the autonomous proliferation of synovial fibroblasts as one of the predisposing genes to RA and could be a target for a novel therapeutic strategy for RA.

Aneurysms of the renal arteries associated with segmental arterial mediolysis in a case of polyarteritis nodosa

This is the first report of segmental arterial mediolysis (SAM) accompanied with polyarteritis nodosa (PN), and manifesting aneurysms of the renal arteries. A 73‐year‐old woman was admitted to hospital because of a high fever. Laboratory tests showed leukocytosis with increased CRP level in the serum. Myeloperoxidase‐anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) and proteinase 3 (PR3)‐ANCA were negative. There were no signs indicating infection or malignancy. After admission renal function rapidly deteriorated. Treatment was then started with daily oral prednisolone and hemodialysis. On the 40th day of hospitalization the patient suddenly became comatose. Cranial CT showed a subarachnoid hemorrhage. The patient died and an autopsy was performed. The pathological findings showed necrotizing vasculitis of the small arteries in various organs, but not associated with that of arterioles or renal glomerular lesions, indicating PN. Unexpectedly, the segmental arteries of the bilateral kidneys showed vascular lesions of dissecting aneurysms, indicating SAM. This case indicates that SAM is one of the causes of aneurysms in PN and is clinically important when the clinical course of PN patients rapidly advances.

Genetic dissociation of dacryoadenitis and sialadenitis in a Sjögren's syndrome mouse model with common and different susceptibility gene loci.

PURPOSE Sjögrens syndrome (SS) is a systemic autoimmune disease in which the main lesions are dacryoadenitis and sialadenitis. It is unclear whether these lesions develop in a common genetic background. A quantitative trait locus (QTL) analysis was performed in the SS mouse model, MRL/MpJ-lpr/lpr (MRL/lpr), to identify the susceptibility loci to dacryoadenitis and sialadenitis and the association with both loci. METHODS MRL/lpr, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/lpr x C3H/lpr) F1, and (MRL/lpr x C3H/lpr) F2 intercross mice were prepared, and the severity of dacryoadenitis and sialadenitis in individuals was quantified by histopathologic grading. In genomic DNA samples from the F2 mice, the polymorphic microsatellite markers highly associated with each lesion were determined as susceptibility loci. RESULTS QTLs with significant linkage for dacryoadenitis were mapped on chromosome 1 (the position of maximum logarithm of odds [LOD] score; 64.1 cM), designated Adacm1; chromosome 2 (88.4 cM), Adacm2; and chromosome 5 (63.9 cM), Adacm3. Those for sialadenitis were mapped on chromosome 1 (69.0 cM), Asm3, and chromosome 2 (65.3 cM and 82.1 cM), Asm4 and Asm5. Adacm1/Asm3 and Adacm2/Asm5 seemed to be a common chromosomal region, respectively. MRL-homozygous at Adacm1 and Adacm2 and at Asm3 and Asm5 manifested an additive effect on the development of dacryoadenitis and sialadenitis, respectively, whereas Adacm3 did not. CONCLUSIONS Dacryoadenitis and sialadenitis in MRL/lpr mice are under the control of common and different susceptibility loci, with an allelic combination that leads to regular variations in pathologic phenotypes.

Combined Atypical Carcinoid Tumour and Squamous Cell Carcinoma of the Lung

A 71-year-old man diagnosed with lung cancer in the right lower lobe with invasion to the middle lobe underwent right lower and middle lobectomy with mediastinal lymph node dissection. The cancer was pathologically diagnosed as stage IIB (pT3N0M0) with combined squamous cell carcinoma and an atypical carcinoid tumour. To the best of our knowledge, this is the first report of a combined atypical carcinoid tumour and non-small cell lung cancer. This case further expands the histological spectrum of combined neuroendocrine tumours.

An unusual case of subclinical diffuse glucagonoma coexisting with two nodules in the pancreas: characteristic features on computed tomography.

A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT.

Pulmonary hypertension associated with diffuse deposition of pentosidine in pulmonary arterioles

Diabetes induces advanced glycation end products (AGEs) that per se are not only a major cause of oxidative stress but also reduce the plasticity of connective tissue by pathological collagen cross-linking. We describe a case of severe pulmonary hypertension manifesting as a major diabetic complication. Impaired pulmonary arteriolar plasticity attributed to pentosidine, together with increased circulation volume by hyperosmotic pressure and reduction in myocardial compliance by multiple patchy fibrosis, may contribute to the clinical manifestation of severe pulmonary hypertension.

LAPAROSCOPIC FEATURES AND INTEROBSERVER VARIATION OF HISTOLOGICAL DIAGNOSIS IN PATIENTS WITH NON‐ALCOHOLIC FATTY LIVER DISEASE

Background:  There is a lack of information regarding the laparoscopic features and interobserver variation of histological diagnosis in patients with non‐alcoholic fatty liver disease (NAFLD).

Diagnostic Challenge in Pancreatic Sarcoidosis using Endoscopic Ultrasonography.

We herein report a 55-year-old woman who presented with erythema and bilateral hilar lymphadenopathy 4 months prior to the detection of pancreatic lesions on an ultrasound. A skin biopsy showed evidence of sarcoidosis. The largest lesion in the tail of the pancreas was hypoechoic on endoscopic ultrasonography (EUS). The lesion was initially iso-enhanced on contrast enhanced-EUS (CE-EUS) but subsequently became hypoenhanced. The lesion revealed heterogeneous components of both soft and hard tissue on EUS elastography. She was ultimately diagnosed with pancreatic sarcoidosis based on the presence of noncaseating granulomas seen on pancreatic tissue retrieved through an EUS-guided fine needle aspiration biopsy.