Clinical features of a new disease concept, IgG4-related thyroiditis.

OBJECTIVES: Immunoglobulin (Ig)G4-related disease is a recently proposed systemic disorder that includes autoimmune pancreatitis (AIP), Mikulicz's disease, and various other organ lesions. In the present retrospective study, we examined whether thyroid lesions should also be included in IgG4-related disease (Ig4-RD) under the new term IgG4-related thyroiditis. METHOD: We enrolled 114 patients with Ig4-RD, including 92 patients with AIP, 15 patients with Mikulicz's disease, and seven patients with IgG4-related cholangitis, and analysed clinical findings, function, serum values of activity markers, computed tomography (CT) images, and histology of the thyroid gland. RESULTS: Among the 22 patients (19%) in our cohort who were found to have hypothyroidism [thyroid stimulating hormone (TSH) > 4 mIU/L], 11 patients had clinical hypothyroidism [free thyroxine (FT4) < 1 ng/dL] and 11 patients had subclinical hypothyroidism (FT4 ≥ 1 ng/dL). Serum concentrations of IgG, IgG4, circulating immune complex (CIC), and ß2-microglobulin (ß2-MG) were significantly higher in the hypothyroidism group compared with the remaining 92 euthyroid patients, and serum C3 concentration was significantly lower. After prednisolone treatment, TSH values had decreased significantly (p = 0.005) in this group and FT4 values had increased significantly (p = 0.047). CT images showed that the thyroid glands of patients with clinical hypothyroidism had a significantly greater volume than those of the euthyroid and other groups. Pathological analysis of one resected thyroid gland disclosed a focused lesion with infiltration of lymphocytes and IgG4-bearing plasma cells and loss of thyroid follicles. CONCLUSIONS: Thyroid lesions associated with hypothyroidism can be considered as a new disease termed IgG4-related thyroiditis. Awareness of this condition should lead to appropriate corticosteroid treatment that may prevent progression to a fibrous state.

Expression of Tn and sialyl Tn antigens in synovial tissues in rheumatoid arthritis.

OBJECTIVES: The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. Tn and sialyl Tn antigens are tumour-associated carbohydrate antigens which are borne on the core proteins of mucins. The purpose of this study is to investigate the existence of tumour-associated carbohydrate antigens in rheumatoid arthritis (RA). METHODS: . We examined the expression of Tn and sialyl Tn antigens in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry. In addition, mucins from synovial fluid (SF) from RA patients are purified by gel filtration and density gradient ultracentrifugation and the existence of these antigens examined by dot and Western blotting. RESULTS: We found that Tn and sialyl Tn antigens were strongly expressed in synovial cells and infiltrating mononuclear cells on the sublining layer and lymphoid follicles in synovial tissues in RA compared with those in osteoarthritis. Tn and sialyl Tn antigens were detected in purified mucins of SF from RA patients. CONCLUSIONS: Tumour-like synovial hyperplasia cells expressed Tn and sialyl Tn antigens. This finding suggests that the mucins exhibiting with abnormal glycosylation may be in part responsible for synovial hyperplasia, leading to the joint destruction in the pathogenesis of RA.

Phase I/II clinical study of percutaneous vertebroplasty (PVP) as palliation for painful malignant vertebral compression fractures (PMVCF): JIVROSG-0202.

BACKGROUND: The safety and efficacy of percutaneous vertebroplasty (PVP), a new treatment modality for painful malignant vertebral compression fractures (PMVCF) using interventional radiology techniques, were evaluated prospectively. MATERIALS AND METHODS: After confirming the absence of safety issues in phase 1, a total of 33 cases were registered up to and including phase 2. Safety and efficacy were evaluated by National Cancer Institute-Common Toxicity Criteria version 2 and Visual Analogue Scale (VAS) at 1 week after PVP. Based on VAS score decreases, efficacy was classified into significantly effective (SE; > or = 5 or reached 0-2), moderately effective (ME; 2-4), or ineffective (NE; <2 or increase). RESULTS: Procedures were completed in all 33 patients (42 vertebrae). Thirty days after PVP, two patients died of primary disease progression, but no major adverse reactions (>grade 2) were observed. Response rate was 70% (95% confidence interval 54% to 83%) [61% (n = 20) with SE, 9% (n = 3) with ME, and 30% (n = 10) with NE] and increased to 83% at week 4. Median time to response was 1 day (mean 2.4). Median pain-mitigated survival period was 73 days. CONCLUSION: For PMVCF, PVP is a safe and effective treatment modality with immediate onset of action.

Ciliated hepatic foregut cyst. A mucus histochemical, immunohistochemical, and ultrastructural study in three cases in comparison with normal bronchi and intrahepatic bile ducts.

We describe herein the morphologies of three cases of ciliated hepatic cysts and compare them with those of normal bronchi and intrahepatic bile ducts. Grossly, the hepatic cysts were located in the subcapsular region. They were solitary, unilocular, and rather small (less than 4 cm in diameter). Histologically, the cyst wall consisted of four layers: pseudostratified ciliated columnar epithelia with mucous cells, subepithelial connective tissue, smooth-muscle bundles, and an outermost fibrous capsule. The epithelial cytoplasm contained neutral, carboxylated, and sulfated mucus. We noted moderate immunoreactivity to keratin, epithelial membrane antigen, carcinoembryonic antigen, DU-PAN-2 and secretory component; weak immunoreactivity to cytokeratin CAM 5.2, cytokeratin AE1 + 3, and carbohydrate antigen 19-9; and faint or negative immunoreactivity to IgA and IgM. Cilia were immunoreactive to actin and tubulin; smooth muscles were immunoreactive to actin and desmin. Ultrastructural observations revealed definite cilia arranged in a 9 + 2 pattern as well as mucous cells. These morphologic features of the hepatic cysts were similar to those of normal bronchi but different from those of normal bile ducts. Our findings suggest that ciliated hepatic cysts arise from the embryonic foregut and differentiated toward bronchial structures in the liver.

Electrophysiological effects of melperone on isolated rabbit heart muscles.

1. Electrophysiological effects of melperone on isolated atrial and ventricular muscle preparations of the rabbit were studied by a conventional microelectrode technique. 2. Melperone (3.3 microM) prolonged the action potential duration and effective refractory period of the atrial preparations without affecting the maximum rate of depolarization (Vmax). These effects of melperone on action potential duration and effective refractory period were inhibited by a low potassium perfusate (2.7 mM). 3. A high concentration of melperone (16.6 microM) decreased Vmax of atrial preparations. In ventricular muscles, melperone at either concentration decreased Vmax, although the increase in action potential duration was greater than in the atrium. 4. Depression of Vmax of ventricular muscles by melperone was found to be augmented by an increase of stimulation frequency and drug concentration. 5. The rate of onset of rate-dependent block of Vmax in ventricle was increased with drug concentration and frequency of stimulation. However, the time constant of recovery from rate-dependent block was almost constant. The kinetics of rate-dependent block of Vmax by melperone were approximately similar to those of quinidine and disopyramide. Consequently it is concluded that melperone possesses class 1a antiarrhythmic activity as well as class 3 activity.

Comparison of gadobenate dimeglumine with gadopentetate dimeglumine for magnetic resonance imaging of liver tumors.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for magnetic resonance imaging of the liver. METHODS: The contrast agent Gd-BOPTA or Gd-DTPA was administered at a dose of 0.1 mmol/kg to 257 patients suspected of having malignant liver tumors. Dynamic phase images, spin-echo images obtained within 10 minutes of injection, and delayed images obtained 40 to 120 minutes after injection were acquired. All postcontrast images were compared with unenhanced T1-weighted and T2-weighted images obtained immediately before injection. A full safety assessment was performed. RESULTS: The contrast efficacy for dynamic phase imaging was moderately or markedly improved in 90.9% (110/121) and 87.9% (109/124) of patients for Gd-BOPTA and Gd-DTPA, respectively. At 40 to 120 minutes after injection, the cor- responding improvements were 21.7% (26/120) and 11.6% (14/121) for spin-echo sequences and 44.5% (53/119) and 19.0% (23/121) for breath-hold gradient-echo sequences, respectively. The differences at 40 to 120 minutes after injection were statistically significant (P < 0.02). Increased information at 40 to 120 minutes after injection compared with information acquired within 10 minutes of injection was available for 24.0% (29/121) of patients with Gd-BOPTA and for 14.5% (18/124) of patients with Gd-DTPA (P < 0.03). Adverse events were seen in 4.7% (6/128) and 1.6% (2/127) of patients receiving Gd-BOPTA and Gd-DTPA, respectively. The difference was not statistically significant. CONCLUSIONS: The efficacy of Gd-BOPTA is equivalent to that of Gd-DTPA for liver imaging during the dynamic phase and superior during the delayed (40-120 minutes) phase of contrast enhancement. Both agents are safe for use in magnetic resonance imaging of the liver.

Subsegmental transcatheter arterial embolization for small hepatocellular carcinomas: local therapeutic effect and 5-year survival rate.

The local therapeutic effects and 5-year survival rates obtained following subsegmental transcatheter arterial embolization (TAE) therapy for small hepatocellular carcinomas (HCCs) were retrospectively analyzed. A total of 124 nodular-type HCC lesions measuring less than 4 cm in diameter in 100 patients with liver cirrhosis were subjected to the analysis. All lesions became opaque on digital subtraction angiography. Complete necrosis was seen in 64% of 11 resected lesions. Among the remaining 113 lesions, the 1- and 5-year local recurrence rates following one performance of TAE were 18% and 33%, respectively. The 1- and 5-year survival rates were 100% and 53%, respectively. No significant side effect was observed after TAE therapy. Subsegmental TAE therapy significantly improved the long-term survival rates of patients with small HCCs associated with liver cirrhosis as compared with those treated by conventional TAE therapy.

MR imaging of olfactory bulbs and tracts.

Olfactory bulbs are easily detected on coronal T1-weighted MR images. They are situated almost symmetrically opposite either side of the lower end of the olfactory sulci, and, on sagittal images, they are observed as thin soft-tissue bands immediately beneath the frontal lobe base. On axial images they are shown as oval, paramedian structures of intermediate intensity. Visualization of the olfactory tract, however, is not always possible. Our study reveals that, on axial images, detection of the olfactory bulb depends on technical factors; we recommend a 256 x 256 matrix, a 3-mm-thick slice, and less than a 0.6-mm gap. Despite the lack of complete visualization of olfactory bulbs and tracts, MR may be effective in demonstrating diseases of these entities.

Angiomyolipoma of the liver: a collective review.

This review summarizes the clinical and pathological findings of 52 cases of hepatic angiomyolipoma to discern and establish the most pertinent clinical and pathologic characteristics of the tumor. The disease was symptomatic in 60% of the patients. Abdominal pain or distress was the most common symptom, appearing in 37% of the patients, followed by malaise and upper abdominal mass or hepatomegaly. Of the 52 patients, only three (5.8%) showed associated tuberous sclerosis. Antemortem diagnosis of the tumor has been made with increasing frequency with the recent advent of computed tomography (CT) and ultrasound (US). The tumor was usually visualized as a hyperechoic mass by US imaging and as a low density mass less than -20 Housefield units by CT, and was hypervascular on angiography. The tumor was usually yellow to light tan, depending on the amount of fat tissue. Histologically, the tumor was characterized by an admixture of mature fat cells, blood vessels, and smooth muscle cells, with occasional foci of extramedullary hematopoiesis. The amount of smooth muscle component varied and often exhibited hypercellularity, pleomorphism with occasional bizarre giant cells, and moderate motitic activity. These features are considered conducive to an erroneous diagnosis of malignant tumor. However, since no malignant counterpart has been reported, it can easily be accurately differentiated histologically, if one is aware of the entity and can identify the three components of the tumor; blood vessels, smooth muscle cells, and fat. With regard to the histogenesis of angiomyolipoma, primitive mesenchymal cells around blood vessels may be the precursor cells.

Cruveilhier-Baumgarten syndrome in which venous hum disappeared following endoscopic variceal sclerotherapy.

We report a case of Cruveihier-Baumgarten syndrome associated with portal vein thrombosis that developed, slowly during a 2-year period after endoscopic variceal sclerotherapy. The thrombosis led to the disappearance of the venous hum and the dilated abdominal wall veins characteristic of this syndrome. A 73-year-old woman was hospitalized for treatment of esophageal varices in April 1988. Her spleen was markedly enlarged, and the histologic findings of her liver were not consistent with hepatic cirrhosis, but with idiopathic portal hypertension. A venous hum was audible in the upper abdomen. Superior mesenteric angiography revealed a porto-systemic shunt vessel under the abdominal wall, originating from the umbilical vein. She was injected four times with a sclerosant, and this brought about disappearance of the esophageal varices. Two years after the first admission, the venous hum was no longer audible, but there was a recurrence of the esophageal varices. More than 2 years later (4 years after the first admission), ultasonographic study, computed tomography, and angiography showed a large thrombus, which completely obstructed the portal vein at the origin of the umbilical vein, and the development of collateral vessels, seen as a "cavernous transformation."

"Moustache" appearance in craniopharyngiomas: unique magnetic resonance imaging and computed tomographic findings of perifocal edema.

This report describes two cases of craniopharyngioma with perifocal edema. In both patients, computed tomography and magnetic resonance imaging (MRI) revealed that the tumors occupied the suprasellar cistern, invaginated the floor of the 3rd ventricle and were tightly adherent to the ventricular walls. The intraventricular portions of the tumors were cystic, containing protein-rich fluid as suggested by MRI and confirmed by operative findings. There was perifocal edema in the hypothalamus adjacent to the intraventricular tumor, the optic tracts, and the posterior limbs of the internal capsules, resembling the shape of a moustache on axial computed tomographic and MRI scans. The perifocal edema subsided after treatment of the intraventricular tumor by surgical resection or radiation therapy. The "moustache" appearance seems a unique, characteristic feature of perifocal edema, which is observed infrequently with certain craniopharyngiomas.

Prognostic significance of magnetic resonance findings in advanced papillary thyroid cancer.

We assessed the prognostic importance of magnetic resonance (MR) findings in locally advanced papillary thyroid cancer. MR findings, clinical data, and pathologic (and surgical) data for 66 patients, including 51 women and 15 men with a mean age of 57 years, who had primary surgery for papillary thyroid cancers were correlated with prognosis. Mean follow-up was 27.5 months (range, 5-117 months). Recurrence was seen in 18 patients (27%). In univariate analyses, age of 60 years or more (p = 0.0066), male gender (p = 0.0373), six MR findings (tumor size of > or = 4 cm ([p = 0.0002], ill-defined margins ([p < 0.0001], tumor extension of the trachea [p = 0.0337], carotoid artery [p = 0.0028]), esophagus [p < 0.0001], and lymph nodes [p = 0.0005]), and three pathologic findings (tumor extension of soft tissues [p = 0.0288], carotid artery [p = 0.0013], and esophagus [p < 0.0001]) had a significant adverse effect on disease-free survival. In multivariate analyses, tumor size (p = 0.0169) and nodal metastasis (p = 0.0393) determined on MR imaging and pathologic esophageal invasion (p = 0.0016) were the only significant independent variables. Esophageal invasion was accurately diagnosed with MR imaging (94% accuracy). MR findings may contain prognostic importance of locally advanced papillary thyroid cancer.

In vivo anatomical analysis of arterial contact with trigeminal nerve: detection with three-dimensional spoiled grass imaging.

The purpose of this study was to review the normal in vivo neurovascular relationship between the trigeminal nerve and surrounding arteries without the use of volunteers. 290 nerves in 145 cases were reviewed during a 1-year period. Axial source images and multiplanar reconstructed (MPR) images were used to determine the neurovascular contact and direction of contact. Multiplanar volume reformation (MPVR) was used to identify the contact vessels and to demonstrate the relationship between the nerve and arteries. Vascular contact was found in 29% of the 290 nerves (83 nerves). The arteries involved were the superior cerebellar artery (SCA) or the anterior inferior cerebellar artery (AICA). Vascular contact with two arteries was found in 3%. Of the 286 asymptomatic nerves, the nerve was located between the two vessels in 3% and compression was seen in 1%. Three points of vascular contact by the two arteries were identified in one asymptomatic nerve. The direction of contact between the SCA and the nerve was superior (38%), superomedial (32%) or medial (15%) in most cases. The direction of contact between the AICA and the nerve was inferior, inferolateral or lateral in all cases. Vascular contact at the root entry zone (REZ) was noted in 90%. Four nerves were affected by trigeminal neuralgia, one of which touched an artery and two were compressed. It was concluded that arterial contact can be assessed without difficulty but evaluation of vascular compression is not easy.

Effectiveness of dynamic MRI for diagnosing pericicatricial minimal residual breast cancer following excisional biopsy.

The purpose of this study was to investigate the effectiveness of dynamic MRI for diagnosing pericicatricial minimal residual breast cancer following excisional biopsy. Twenty-six patients who underwent excisional biopsy of a tumor or calcified lesion of the breast underwent gadolinium-enhanced dynamic MRI by the fat-saturated 2D fast spoiled gradient echo (SPGR) sequence (group 1), 24 patients by the spectral IR enhanced 3D fast gradient echo (Efgre3d) sequence (group 2). Pericicatricial residual cancer was confirmed histologically in 29 of the 50 patients. The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MRI for residual cancer diagnosis was 66, 81, 72, 83 and 63%. A nodular, thick and discontinuous enhanced rim around the scar is indicative of a residual tumor. However, false-positive findings due to granulation or proliferative fibrocystic change remain limitations.

Hepatic hilar inflammatory pseudotumor mimicking cholangiocarcinoma with cholangitis and phlebitis--a variant of primary sclerosing cholangitis?

Inflammatory pseudotumor (IPT) of the liver is rare. We present a case of hepatic IPT mimicking cholangiocarcinoma in which the tumor was located at the left porta hepatis. The patient was a 64-year-old man in whom abnormal liver function test results had been noted incidentally during an annual health checkup in 1993: the patient declined to go to the hospital for further examination. At the annual health checkup the following year, abnormal liver function test results were noticed again, and this time he did go to a hospital, where a hepatic mass was found. Laboratory test results were unremarkable. Based on the location of the lesion and the findings of a variety of imaging modalities, such as ultrasound and computed tomography examination, the lesion was preoperatively diagnosed as hilar cholangiocarcinoma and was surgically resected. Pathologic examination of the resected lesion, however, revealed that it was not a true tumor but an inflammatory pseudotumor with marked destructive and sclerosing cholangitis mimicking primary sclerosing cholangitis (PSC) and obliterative phlebitis. Since the location and features of the tumor in the present case are very pertinent to the relationship between IPT and PSC, we describe its clinical and histologic features and discuss the findings in relation to PSC in the context of our literature review.

201Tl per-rectal scintigraphy in primary hepatocellular carcinoma.

The results of 201Tl per-rectal scintigraphy in 10 patients with primary hepatocellular carcinoma (HCC) were presented together with the findings from contrast angiography, computed tomography and ultrasonography. 201Tl accumulation within the tumour was seen in seven of ten patients. This accumulation was thought to be due to 201Tl supply not from the portal vein but from the hepatic artery since significantly high heart to liver uptake (H/L) ratio from 0.71 to 1.21 and clear visualization of the heart and kidneys, indicating the presence of abundant portal-to-systemic shunting, were observed. Another three patients showed negative 201Tl accumulation within the tumour and near-normal H/L ratios from 0.32 to 0.47 which indicates little portal-to-systemic shunting. This finding reveals the evidence of the lack of 201Tl supply to the tumour from the portal vein. It seems that HCC does not receive any significant amount of blood flow from the portal system.

Variable loading cholangiomanometry and clinical applications.

We have designed a variable loading cholangiomanometric method, which permits a precise and objective evaluation of distal bile duct function. Normal resistance (R) values (1-7 units) and residual pressure (P) values (50-150 mm H2O) have been defined by this method. We have performed this procedure on 138 patients with cholelithiasis, and have found that 13 patients with cholecystolithiasis and 14 patients with choledocholithiasis have elevated R and P values in the distal bile duct. These patients also had morphological abnormalities in the distal bile duct. There was a high percentage of patients with abnormal pressure/flow curves at high flow rates among patients with morphologically dilated bile ducts. Division of pressure/flow curve patterns at low flow rates into three types made it possible to differentiate between functional and structural abnormalities. Patients in whom the residual P values were high and morphological defects of the distal bile duct. The possible application of these measurements in determining the need for additional surgery on the inferior bile duct, particularly papilloplasty, is discussed.

MR diagnosis of myelofibrosis.

We present a case of secondary myelofibrosis in which magnetic resonance imaging (MRI) contributed to the diagnosis. On both T1- and T2-weighted images, bone marrow showed hypointensity. However, since blood transfusion therapy was performed prior to MRI, it was necessary to differentiate fibrosis from siderotic marrow. On gradient echo (GRASS) images, bone marrow also showed hypointensity, but not as prominent as that seen in siderotic marrow. After intravenous administration of gadolinium-dimethylene triaminepentaacetic acid (Gd-DTPA), enhancement of the marrow space may be induced by a fibrous change of the marrow. MR findings were confirmed by histological examination of the biopsy specimen.

Computed tomography during arterial portography in idiopathic portal hypertension.

Computed tomography (CT) during arterial portography was performed in two cases of idiopathic portal hypertension (IPH). Multiple patchy low-density areas with unclear margins and abnormally short distances between some of the medium-sized portal branches and the liver surface were demonstrated. These findings were distinctly different from those of liver cirrhosis. CT during arterial portography was useful for differentiating IPH from liver cirrhosis.

CT arteriographic confirmation of focal hepatic fatty infiltration adjacent to the falciform ligament associated with drainage of inferior vein of Sappey: a case report.

We experienced a case of focal fatty infiltration in the anteromedial edge of the medial segment of the liver adjacent to the falciform ligament associated with advanced esophageal cancer. By using CT during selective right internal thoracic arteriography, we confirmed that the inferior vein of Sappey drained into the area of focal fatty infiltration. This is the first case to directly establish the relationship between drainage of the inferior vein of Sappey and occurrence of focal fatty infiltration of the liver.