Clinical and echocardiographic characteristics for differentiating between transthyretin-related and light-chain cardiac amyloidoses.

Differential diagnosis between transthyretin (TTR) and immunoglobulin light-chain (AL) cardiac amyloidoses is essential due to significantly different prognoses and therapeutic options. Therefore, clinical characteristics of patients with biopsy-proven cardiac amyloidosis were investigated to differentiate TTR from AL amyloidosis. From September 2006 to May 2014, 46 patients were confirmed to have cardiac amyloidosis (TTR, n = 28; AL, n = 18) in our institute. The median age of patients with TTR amyloidosis was 78 years (range 61-90) with 27 (96 %) males, while that of patients with AL amyloidosis was 66 (range 52-76) with 12 (67 %) males. There were no statistically significant differences in echocardiographic findings regarding left ventricular (LV) systolic function or diastolic dysfunction between the two groups. Interestingly, serum brain natriuretic peptide (BNP) levels in patients with AL amyloidosis were significantly higher than those in TTR amyloidosis patients. In contrast, the LV wall was significantly thicker in patients with TTR amyloidosis than in those with AL amyloidosis. Therefore, the ratio of BNP to LV mass index (LVMI) at presentation in AL amyloidosis patients was significantly higher than that in TTR patients (6.7 vs 2.9, p = 0.0006). A BNP-LVMI ratio of less than 3.5 had a diagnostic sensitivity and specificity for TTR amyloidosis of 71 and 83 %, respectively. One-year overall survival was 88.7 % in the patients with TTR amyloidosis and 23.7 % in the patients with AL amyloidosis. Our analysis indicates that the BNP-LVMI ratio, as well as age and sex, may be useful parameters for distinguishing TTR from AL cardiac amyloidosis.

Impact of clinical and echocardiographic characteristics on occurrence of cardiac events in cardiac amyloidosis as proven by endomyocardial biopsy.

BACKGROUND: Although patients with immunoglobulin light chain (AL) cardiac amyloidosis exhibit worse outcomes than those with transthyretin (TTR) cardiac amyloidosis, few data exist regarding the occurrence of cardiac events and the echocardiographic indices in endomyocardial biopsy (EMBx) proven amyloidosis. METHODS: From November 2007 to October 2012, we identified 33 patients with EMBx-proven amyloidosis. There were 12 patients (8 men; mean age: 66 years) with AL and 21 patients (20 men; mean age: 78 years) with TTR. We performed serial echocardiography and observed the patients during follow-up; defining all-cause mortality as the primary endpoint and hospitalization for heart failure as the secondary endpoint. RESULTS: The survival rates at 12 months were 20.8% and 85.7% in AL and TTR, respectively (p<0.001). The cumulative incidences of the composite of death or readmission for heart failure at 12 months were 91.7% and 51.3% in AL and TTR, respectively (p<0.001). A multivariate analysis showed that the AL type amyloid was the powerful predictor of mortality (hazard ratio: 8.50, 95% confidence interval: 1.79 to 40.57, p<0.05). Under these conditions, the E/e' in AL tended to increase from 23±13 to 28±11 (p=0.06) with marked increases in B-type natriuretic peptide (779±456 pg/ml to 1576±895 pg/ml, p<0.05), although these remained unchanged in TTR, which exhibited significantly increased left ventricular end-diastolic dimensions from 40±4 mm to 42±4 mm (p<0.05). CONCLUSIONS: The survival rate was generally worse in AL cardiac amyloidosis, although the readmission for heart failure remains high in TTR cardiac amyloidosis with the occurrence of left ventricular dilatation.

[A long survival of a patient with poor performance status who suffered from advanced right breast cancer with multiple lung metastases controlled by trastuzumab as a key drug].

We report a case of a 60-year-old woman with poor performance status (PS). She suffered from advanced right breast cancer with multiple lung metastases, which was controlled by chemotherapy with trastuzumab as the key drug. The patient presented with a 4 cm-sized large right breast mass. Her PS was poor due to progressive spinocerebellar degeneration. The biopsy specimen of the breast mass showed scirrhous type of the invasive ductal carcinoma (ER+, HER2 2+). Multiple lung metastases were also detected by computed tomography. Considering her poor PS, the patient was treated with mild systemic therapy using trastuzumab as the key drug. A different drug response was achieved between the breast mass and lung metastatic lesions, and the tumors were maintained as stable disease (SD) during first 18 months. However, she finally passed away due to respiratory failure resulting from lung metastasis, 33 months after starting treatment. The autopsy findings showed a difference of HER2 expression between the breast tumor and lung metastatic lesions. It must be recognized that differences of HER2 expression between the primary tumor and metastatic lesions are sometimes demonstrated in patients with breast cancer, and that trastuzumab can be used as a key drug in some patients as in the current case.

Etiological factors in primary hepatic B-cell lymphoma.

Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p < 0.01 for both). Two hepatic DLBCL cases (16.7%) had rheumatoid arthritis treated with methotrexate, and four MALT lymphoma cases (50%) had Sjögren's syndrome, primary biliary cirrhosis, or autoimmune hepatitis; one case in each of these two groups was complicated by chronic HCV-seropositive hepatitis. Although primary hepatic lymphoma is rare, persistent inflammatory processes associated with HCV infection or autoimmune disease may play independent roles in the lymphomagenesis of hepatic B cells.

Undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi: report of a case.

We report a case of undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi. A 73-year-old man presented with general malaise. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the distal common bile duct, accompanied by dilatation of the intra- and extrahepatic bile ducts. The patient underwent pancreaticoduodenectomy with regional lymphadenectomy. Gross examination revealed that the distal common bile duct was obstructed by an elastic hard mass, 3.2 × 2.6 cm, accompanied by intraductal tumor thrombi. Microscopically, the nodule was well defined and composed of atypical large tumor cells with bizarre nuclei and little cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin-7 and CAM5.2, but negative for CD56, chromogranin A, and synaptophysin. Thus, a histological diagnosis of undifferentiated carcinoma of the common bile duct was made. The patient recovered uneventfully and has remained free of any signs of recurrence for 18 months since the operation. Undifferentiated carcinomas of the extrahepatic bile duct can be detected early, with the chance of a good prognosis; however, because their biologic growth behavior is still considered aggressive, careful observation after surgery and the initiation of multidisciplinary treatment against recurrence are necessary.

Fibro-fatty volume of culprit lesions in Virtual Histology intravascular ultrasound is associated with the amount of debris during carotid artery stenting.

OBJECTIVES: This study aimed to evaluate the relationship between the amount of aspirated debris during distal balloon-protected carotid artery stenting (CAS) and the pre-intervention plaque composition, as assessed by Virtual Histology (VH) intravascular ultrasound (IVUS). METHODS: The study subjects were 25 consecutive patients (mean age, 73.0 +/- 5.2 years; 20 males and 5 females) who underwent CAS under distal balloon protection. The average rate of carotid stenosis was 74.6 +/- 12.9% by North American Symptomatic Carotid Endarterectomy Trial criteria. We assessed culprit plaque components by VH-IVUS before CAS. Aspirated debris was filtered, stained with HE and mounted onto glass slides. The quantity of debris was evaluated by measuring its surface area. We evaluated the relationship between the quantity of aspirated debris and VH-IVUS measurements before CAS. RESULTS: The amount of debris during CAS was positively correlated with the total plaque volume in grayscale IVUS (Rs = 0.480, p = 0.015) and fibro-fatty volumes over the entire lesion length in VH-IVUS (Rs = 0.561, p = 0.001). CONCLUSIONS: Culprit lesions with large plaque volumes, especially larger fibro-fatty volumes, as imaged by VH-IVUS, are associated with large amounts of debris during balloon-protected CAS.

Inactivation of amyloid-enhancing factor (AEF): study on experimental murine AA amyloidosis.

It is known that amyloid-enhancing factor (AEF) shortens the preamyloid phase in experimentally induced AA amyloidosis in mice. Because it is reported that AEF serves as both a nidus and a template for amyloid formation, AA amyloidosis may have transmissibility by a prion-like mechanism. It has been shown that amyloid fibrils also have AEF activity, and amyloid fibrils with AEF activity were named fibril-amyloid enhancing factor (F-AEF). In this study, we investigated methods to inactivate the AEF activity. AEF was extracted from the thyroid gland obtained at autopsy of a patient with AA amyloidosis. Before injection into mice, AEF was treated with several methods for inactivation. Of all the tested treatments, 1 N NaOH, 0.1 N NaOH, and autoclaving consistently demonstrated complete inactivation of AEF. Heat treatment led to incomplete inactivation, but 0.01 N NaOH, 0.001 N NaOH, pepsin, trypsin, pronase, and proteinase K treatment had no effect on AEF activity. By analysis with transmission electron microscopy, the AEF preparation contains amyloid fibrils, and a change of ultrastructure was shown after 1 N NaOH, 0.1 N NaOH, and autoclaving treatment. Furthermore, immunoblotting of AEF with antihuman AA antibody revealed that the protein band was scarcely found after autoclaving, 1 N NaOH, and 0.1 N NaOH treatment. Our results suggest that, similar to Creutzfeldt-Jakob disease (CJD), amyloidosis may require chemical or autoclaving decontamination.

Human gastroepiploic artery has greater chymase activity than the internal thoracic artery.

OBJECTIVE: Recent reports have demonstrated that long-term patency of the gastroepiploic artery (GEA) in coronary artery bypass grafting (CABG) is less satisfactory compared with the internal thoracic artery (ITA). However, the reason has not been fully elucidated. Angiotensin II is known to play an important role in the development of intimal hyperplasia, we hypothesized that the GEA is different from the ITA with respect to angiotensin II-forming ability. Accordingly, we measured activities of angiotensin II-forming enzymes, angiotensin-converting enzyme (ACE) and chymase, in human GEA and ITA. METHODS: Remnant of the GEAs and ITAs were obtained from 24 patients who underwent CABG in which both conduits were used simultaneously. Activities of ACE and chymase were measured by using the extract form the GEA or ITA. Sections of the GEA or ITA were immunohistochemically stained with anti-human chymase antibody. RESULTS: The ACE activity of the GEA (0.28+/-0.16 mU/mg protein) was greater than that of the ITA (0.18+/-0.11, p < 0.001). The chymase activity of the GEA (11.11+/-7.15 mU/mg protein) was also greater than that in the ITA (7.13+/-4.89, p < 0.001). The density of chymase-positive cells in the GEA (3.8+/-4.2 cells/mm2) was greater than that in the ITA (1.1+/-1.2, p < 0.01). CONCLUSION: Activities of both ACE and chymase were significantly greater in the GEA compared with the ITA. The GEA may be different from the ITA with respect to potential ability of angiotensin II-formation.

A serous oligocystic adenoma of the head of the pancreas successfully treated by dome resection and chemocautery: a new approach to serous oligocystic adenoma.

Serous oligocystic adenoma (SOA) is an extremely rare benign tumor and ill-demarcated large cyst. We report a case of pancreatic SOA. During abdominal ultrasonography (US) for a routine health examination and computed tomography (CT), a 69-year-old woman was found to have a 9-cm unilocular cyst located in the head of her pancreas. After a 2-year follow up, the cyst was seen to increase in size. The results of US, CT, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography (ERCP), and angiography led to suspicion of a benign or low grade malignancy cystadenoma of the pancreas adjacent to the peripheral organs. Fluid analysis and frozen section pathological studies revealed a serous oligocystic adenoma with no malignancy. Dome resection, chemocautery, and omental filling were performed, and the postoperative course was uneventful. SOAs are difficult to diagnose without surgery. When the cyst exists in the head of the pancreas, adjacent to the biliary tract, portal system, or visceral vessels, it is also difficult to perform complete resection without the threat of morbidity or mortality. We have developed a new approach to SOA diagnosis and treatment that involves minimally invasive procedures.