Kotaro Yoshida

IgG4-Related Disease: Dataset of 235 Consecutive Patients

AbstractImmunoglobulin G4-related disease (IgG4-RD) is a recently discovered systemic condition, in which various organ manifestations are linked by a similar histological appearance. Our knowledge of this condition is still fragmented, as most studies have examined only a few dozen patients or focused on a particular organ manifestation. This study was conducted to learn the demography and patient characteristics of IgG4-RD using a large cohort. A total of 235 consecutive patients with IgG4-RD, diagnosed in 8 general hospitals in the same medical district, were identified by searching the institutions’ radiology database. Inclusion criteria were histology-proven IgG4-RD according to the Pathology Consensus Statement and/or definitive type 1 autoimmune pancreatitis meeting the International Consensus Diagnostic Criteria. Clinical notes and images of selected patients were retrospectively reviewed. All patients were adults (M/F = 4/1). The median age was 67 years (range 35–86). Nine tenths were diagnosed in their 50s to 70s. Among 486 manifestations identified in total, the most common was pancreatitis diagnosed in 142 patients (60%), followed by sialadenitis (34%), tubulointerstitial nephritis (23%), dacryoadenitis (23%), and periaortitis (20%). The majority of patients (95%) had at least 1 of the 5 most common manifestations. Male and female patients differed in their organ manifestations (periaortitis more common in males and sialodacryoadenitis more common in females). Serum IgG4 (normal ⩽135 mg/dL) was elevated to >135 mg/dL in 208 patients (88%) and >270 mg/dL in 167 (71%). The IgG4 value was significantly higher in patients with multiorgan involvement than in those with a single manifestation (median 629 mg/dL vs 299 mg/dL, P < 0.01). Of 218 patients, for whom both IgG4 and IgG values were available, the IgG4/IgG ratio was raised to >10% in 194 (89%). Corticosteroids were effective, but the relapse rate was estimated to be 24% in the study period (median 37 months). During the follow-up, 15 malignant diseases were diagnosed in 13 patients (6%). This figure is similar to the incidence (12.9 cancers) expected from the Japanese nationwide study for cancer epidemiology (standardized incidence ratio 1.16). In conclusion, this reliable dataset could improve the characterization of IgG4-RD, particularly its unique demography and the frequency of each organ manifestation.

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

The class II α-isoform of phosphatidylinositol 3-kinase (PI3K-C2α) is localized in endosomes, the trans-Golgi network and clathrin-coated vesicles; however, its functional role is not well understood. Global or endothelial-cell–specific deficiency of PI3K-C2α resulted in embryonic lethality caused by defects in sprouting angiogenesis and vascular maturation. PI3K-C2α knockdown in endothelial cells resulted in a decrease in the number of PI3-phosphate–enriched endosomes, impaired endosomal trafficking, defective delivery of VE-cadherin to endothelial cell junctions and defective junction assembly. PI3K-C2α knockdown also impaired endothelial cell signaling, including vascular endothelial growth factor receptor internalization and endosomal RhoA activation. Together, the effects of PI3K-C2α knockdown led to defective endothelial cell migration, proliferation, tube formation and barrier integrity. Endothelial PI3K-C2α deficiency in vivo suppressed postischemic and tumor angiogenesis and diminished vascular barrier function with a greatly augmented susceptibility to anaphylaxis and a higher incidence of dissecting aortic aneurysm formation in response to angiotensin II infusion. Thus, PI3K-C2α has a crucial role in vascular formation and barrier integrity and represents a new therapeutic target for vascular disease.

Solid serous cystadenoma of the pancreas: MR imaging with pathologic correlation

We report a case of solid type serous cystadenoma of the pancreas. Computed tomographic and magnetic resonance (MR) images showed a hypervascular solid tumor that was difficult to differentiate from endocrine tumor of the pancreas. However, the tumor showed marked hyperintensity similar to that of hepatic cyst on MR cholangiopancreatography, indicating not a solid but rather a cystic nature. MR cholangiopancreatography (heavily T2-weighted image) is quite useful for clearly differentiating solid from cystic tumors.

Hepatocellular Carcinoma with β-Catenin Mutation: Imaging and Pathologic Characteristics.

PURPOSE To identify the imaging features of hepatocellular carcinoma (HCC) associated with β-catenin mutation and their relationship to pathologic findings. MATERIALS AND METHODS Institutional ethics committee approval and informed consent were obtained. One hundred thirty-eight surgically resected HCCs were analyzed in this study. Immunohistochemical expression of β-catenin and its transcriptional product, glutamine synthetase (GS), were graded and classified into three groups: the β-catenin positive and GS positive group (HCC with β-catenin mutation), the β-catenin negative and GS positive group (intermediate HCC), and the β-catenin negative and GS negative group (HCC without β-catenin mutation). Clinical, pathologic, and imaging findings from dynamic computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance (MR) imaging (T1-weighted, T2-weighted, diffusion-weighted, and hepatobiliary phase imaging) were evaluated. Correlations among immunohistochemical expression of β-catenin, GS, and organic anion transporting polypeptide 1B3 (uptake transporter of gadoxetic acid) were evaluated. The χ(2), Kruskal-Wallis, and Spearman correlation tests were used. RESULTS HCCs with β-catenin mutation (n = 27) showed a lower median contrast-to-noise ratio at diffusion-weighted imaging than did intermediate HCCs (n = 23) and HCCs without β-catenin mutation (n = 84) (13.2, 24.4, and 27.0, respectively; P = .02), higher apparent diffusion coefficient (1.33, 1.13, and 1.12, respectively; P < .0001), higher contrast-to-noise ratio (0.58, -28.7, and -45.0, respectively; P < .0001) and higher enhancement ratio during the hepatobiliary phase (0.90, 0.50, and 0.42, respectively; P < .0001). At pathologic examination, HCCs with β-catenin mutation showed pseudoglandular proliferation and bile production with a higher grade of differentiation (P = .04, .001, and .005, respectively). There were significant positive correlations among expression of β-catenin, GS, and organic anion transporting polypeptide 1B3 (P < .0001). CONCLUSION HCCs with β-catenin mutation showed a higher grade of differentiation with frequent pseudoglandular patterns and bile production, and characteristic imaging findings included a high enhancement ratio at gadoxetic acid-enhanced MR imaging and a high apparent diffusion coefficient at diffusion-weighted imaging. Online supplemental material is available for this article.

Hepatic pseudolymphoma: imaging–pathologic correlation with special reference to hemodynamic analysis

ObjectivesTo clarify radiological findings and hemodynamic characteristics of hepatic pseudolymphoma, as compared with the histopathological findings.MethodsRadiological findings of ten histopathologically confirmed hepatic pseudolymphomas in seven patients were examined using US, CT, and MRI. Six patients also underwent angiography-assisted CT, including CT during arterial portography (CTAP) and CT during hepatic arteriography (CTHA) to analyze hemodynamics.ResultsThe nodules were depicted as hypoechoic on US, hypodense on precontrast CT, hypointense on T1-weighted images, and hyperintense on T2-weighted images. On contrast-enhanced CT/MRI, they showed various degrees of enhancement, and sometimes, perinodular enhancement was observed at the arterial dominant and/or equilibrium phase. On CTAP, the nodules showed portal perfusion defects, including some in the perinodular liver parenchyma. On CTHA, irregular bordered enhancement was observed in perinodular liver parenchyma on early phase, and continued until delayed phase. Some nodules had preserved intra-tumoral portal tracts. Histopathologically, the nodules consisted of marked lymphoid cells. In perinodular liver parenchyma, stenosis or disappearance of portal venules, caused by lymphoid cell infiltration in the portal tracts, was observed.ConclusionsHepatic pseudolymphoma showed some characteristic radiological findings including hemodynamics on CT, MRI, and angiography-assisted CT. These findings are useful in the differentiation from hepatocellular carcinoma and other tumors.

Adenosquamous carcinoma of pancreas: CT and MR imaging features in eight patients, with pathologic correlations and comparison with adenocarcinoma of pancreas

PurposeTo reveal the CT and MR imaging features of adenosquamous carcinoma of pancreas (ASqC) in eight patients.MethodsThis study was approved by our institutional review board. Eight patients with ASqC were included in this study. Radiologic and pathologic findings were reviewed in each lesion. Additionally, radiologic imaging findings were compared between ASqC and controlled adenocarcinoma groups.ResultsSignificant differences between ASqC and adenocarcinoma groups were noted in lesion shape, enhancement pattern on dynamic CT images, the presence or absence of necrosis, and tumor thrombus in the portal vein (PV) system. Compared with adenocarcinoma, ASqC tended to be round-lobulated shape (100% vs. 57.6%), have necrotic portions (100% vs. 39.4%), and have tumor thrombus in the PV system (37.5% vs. 6.1%). Extensive central necrosis was found in six (75%) of ASqC lesions. More lesions in ASqC group (62.5% vs. 12.1%) showed the highest absolute attenuation on pancreatic arterial phase (PAP) or portal venous phase (PVP) images, although the average attenuation values of all ASqC lesions on PAP, PVP, and delayed phase images were almost the same. Five (83.3%) of six resected lesions appeared as nodular type macroscopically. Microscopically, all lesions did not show infiltrating growth pattern, but showed an intermediate growth pattern, and were surrounded incompletely by fibrous tissue.ConclusionsASqC tended to be a round-lobulated lesion with extensive central necrosis. Additionally, tumor thrombus in the PV system was often present. These CT and MR imaging features could be a useful clue for diagnosing ASqC.

Correlation between Gd-EOB-DTPA-enhanced MR imaging findings and OATP1B3 expression in chemotherapy-associated sinusoidal obstruction syndrome.

We report a female case of sinusoidal obstruction syndrome (SOS) diagnosed pathologically after chemotherapy (Pmab+m-FOLFOX6) for ascending colon cancer with multiple liver metastases, focusing on the findings of gadoxetic acid-enhanced MRI (EOB-MRI) and the organic anion transporting polypeptide 1B3 (OATP1B3) expression of in the liver. The patient was a 75-year-old female. She had received chemotherapy (Pmab+m-FOLFOX6) as six cycles for preoperative chemotherapy. After the preoperative chemotherapy, tumor sizes of hepatic metastases were reduced and hepatobiliary phase of EOB-MRI clearly depicted diffuse reticular hypointensity in the background liver. On the other hand, dynamic CT and/or other sequences of EOB-MRI did not show definite abnormality in the background liver. After the operation, this patient was pathologically confirmed as SOS demonstrating centrilobular congestion, sinusoidal dilatation, and perisinusoidal fibrosis. In normal liver parenchyma, OATP1B3 (uptake transporter of the EOB-MRI) expression is observed predominantly in centrilobular hepatocytes (zone 3). On the other hand, OATP1B3 expression was remarkably reduced because of the damages in the centrilobular (zone 3) hepatocytes in this SOS case. This indicated that EOB-MRI might be extremely sensitive in diagnosing SOS in its early stage.

Imaging and pathological features of gastric lesion of immunoglobulin G4-related disease: A case report and review of the recent literature.

Abstract We describe a 67-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with optic neuropathy, dacryoadenitis, periaortitis, retroperitoneal fibrosis, and a gastric mass-like lesion. A mass-like lesion measuring 52 × 40 mm in the antrum of the stomach was found incidentally through whole-body screening for other organ involvement of IgG4-RD using contrast-enhanced computed tomography (CT). Histology of the stomach revealed that the lesion was also IgG4-related and was located in the submucosal layer extending to the subserosal region. This case suggests that the stomach can also be a site of involvement of IgG4-RD.

Gadoxetic Acid Enhanced Magnetic Resonance Imaging Reflects Co-activation of β-catenin and Hepatocyte Nuclear Factor 4α in Hepatocellular Carcinoma

The aim of this study is to clarify the correlation of the co‐activation of β‐catenin and hepatocyte nuclear factor (HNF)4α with the findings of gadoxetic acid‐enhanced magnetic resonance imaging (MRI), organic anion transporting polypeptide (OATP)1B3 expression, and histological findings in hepatocellular carcinoma (HCC).

Isolated Arteries Originating from the Intrahepatic Arteries: Anatomy, Function, and Importance in Intervention

Isolated hepatic arteries are defined as hepatic terminal arterioles that are not accompanied by portal venules or bile ductules and penetrate the liver parenchyma and distribute to the hepatic capsule and intrahepatic hepatic veins. Abundant communications exist between intra- and extrahepatic arteries through isolated arteries and capsular arterial plexus. They play a principal role in the development of subcapsular hemorrhage and arterial collateral formation following transcatheter arterial chemoembolization for liver cancers. The anatomy, function, and clinical importance of isolated hepatic arteries in interventional radiology, especially regarding subcapsular hemorrhage and arterial collateral formation, are highlighted in this article.