'Localized amyloidosis': 123I-labelled SAP component scintigraphy and labial salivary gland biopsy

In apparently localized amyloidosis, there is no appropriate test to determine whether systemic deposits exist. We studied the value of serum amyloid P component (SAP) scintigraphy and labial salivary gland (LSG) biopsy on patients with apparently localized amyloidosis in 12 patients who had neither clinical nor biological evidence of systemic amyloidosis. All patients had an LSG biopsy and echocardiography. Iodine-123-labelled serum amyloid P component (123I-SAP) scintigraphy was performed in all patients. Whole-body scintigraphy was done, and tissue retention was evaluated at 24 h and 48 h. Of these 12 patients, three had amyloidosis in their LSG and had abnormal 123I-SAP scintigraphy; these three had a secondary clinical history of systemic amyloidosis. Three other patients had abnormal 123I-SAP scintigraphy without detectable systemic amyloid deposits, but one had a previous history of bilateral carpal tunnel syndrome treated with infiltration. 123I-SAP scintigraphy in association with LSG biopsy may be helpful in determining the localized or systemic character of amyloid disease.      

Stiff Heart Syndrome

Isolated cardiac amyloidosis, or “Stiff Heart Syndrome,” is a rare manifestation of amyloidosis. Some degree of cardiac amyloid deposition is common in elderly patients, as reported in prior post-mortem studies; however, isolated cardiac involvement with predominantly cardiac symptoms and no evidence of systemic disease is a rare presentation. Establishing the correct diagnosis, even with the use of extensive testing including amyloid typing, understanding the clinical significance, and management can be challenging in such cases.     

Striking cholestatic liver disease: a distinct manifestation of advanced primary amyloidosis

In patients with systemic amyloidosis, amyloid fibrils are typically deposited in numerous organs, including the kidneys, heart, and liver. Although amyloid deposition in the liver is common in patients with systemic amyloidosis, clinical liver disease is relatively rare. The patient described here had cholestatic liver disease as the primary manifestation of primary systemic amyloidosis. Review of the literature suggests that prominent liver disease with cholestasis is unusual but probably underreported in patients with amyloidosis and appears to be restricted to patients with the primary form of amyloidosis. Nonetheless, cholestatic hepatic amyloidosis is characterized by distinct clinical, laboratory, and pathologic features; recognition of this process is critical because it identifies patients with widespread organ involvement and portends a poor prognosis.     

Bladder wall thickness on ultrasonographic cystourethrography: affecting factors and their implications.

OBJECTIVE: To explore factors affecting bladder wall thickness on ultrasonographic cystourethrography in female patients with lower urinary tract symptoms. METHODS: The records of 492 female patients with lower urinary tract symptoms who had undergone a urodynamic study and ultrasonography of the lower urinary tract and who had normal urinalysis findings, negative urine culture results, or both were identified from our urogynecologic database. These included 248 patients with urodynamic stress incontinence, 38 with detrusor overactivity, 39 with mixed incontinence, 35 with a hypersensitive bladder, 42 with voiding difficulty, and 90 with normal urodynamic findings. RESULTS: Age, resting bladder neck angle, urethral mobility, and maximum urethral closure pressure were significantly associated with bladder wall thickness at the trigone and dome. Bladder wall thickness at the trigone was correlated with that at the dome (P < .0001). Bladder wall thickness at the trigone was positively correlated with pressure transmission ratios in the first and second quarters of the urethra (P < .0001; P = .002, respectively), whereas that at the dome was positively correlated with intravesical pressure at maximum flow and with detrusor opening pressure (P = .027; P = .046, respectively). Age and intravesical pressure at maximum flow were independently associated with bladder wall thickness at the trigone and dome (P = .007; P = .028), respectively. A thickened bladder wall was a common finding in female lower urinary tract symptoms, except in the patients with a hypersensitive bladder. CONCLUSIONS: Demographic, anatomic, and urodynamic factors may affect the bladder wall thickness at the trigone, dome, or both.     

Primary systemic amyloidosis--a diagnostic primer

Primary systemic amyloidosis (immunoglobulin light chain-derived) (AL) is an uncommon dysproteinemia with highly varied initial clinical manifestations. Among 153 patients with this disorder, the median survival was 20.4 months (5-year survival, 19.6%). The worst outcome was associated with overt congestive heart failure (median survival, 7.7 months; 5-year survival, 2.4%). The patients with the best outcome were those who had amyloid neuropathy without associated cardiac or renal involvement (median survival, 39.7 months; 5-year survival, 31.6%). Serum protein electrophoresis and immunoelectrophoresis are the most important tests because a monoclonal protein can be detected in almost two-thirds of the patients. When screening of both serum and urine is performed, a monoclonal protein is found in 86% of patients. Such screening is helpful if primary systemic amyloidosis is to be detected and treated early.     

膀胱肿瘤及前列腺增生同期经尿道切除的中期随访结果

目的评估同时行经尿道膀胱肿瘤电切（TURBT）和前列腺汽化切除（TUVP）治疗非肌层浸润性膀胱肿瘤合并有严重下尿路症状前列腺增生患者的疗效。方法对2004年至2008年期间45例行TURBT＋TUVP和126例单纯行TURBT的非肌层浸润性膀胱肿瘤患者的肿瘤复发率、进展率和后尿道种植率进行比较。结果TURBT＋TUVP组的肿瘤复发率、进展率和后尿道种植率分别为26.7%、8.9%和4.4%;TURBT组分别为27.8%、8.7%和4.8%,两组比较差异无统计学意义（P〉0.05）。结论同时行TURBT＋TUVP治疗非肌层浸润性膀胱肿瘤合并有严重下尿路症状的前列腺增生患者是安全、有效的。     

Serial echocardiographic observations in patients with primary systemic amyloidosis: an introduction to the concept of early (asymptomatic) amyloid infiltration of the heart

Echocardiography was used for the serial assessment of 27 patients with primary systemic amyloidosis. Thirteen patients had no clinical cardiac deterioration between the two echocardiographic studies (group 1), whereas in 14 patients (group 2), congestive heart failure or arrhythmias (or both) appeared or worsened during a mean observation period of 19 months. The only echocardiographic changes in group 1 were a mild increase in left ventricular mass and a mild decrease in left ventricular wall systolic thickening. Patients in group 2 had significant changes in left ventricular wall thickness (mean increase, 34%), in left ventricular mass (mean increase, 42%), in right ventricular wall thickness (mean increase, 78%), in left atrial size (mean increase, 19%), in left ventricular mass/voltage ratio (mean increase, 68%), in left ventricular radius/thickness ratio (mean decrease, 29%), and in left ventricular fractional shortening (mean decrease, 13%). Significant correlations were found in group 2 between changes in systolic and diastolic blood pressure and changes in ventricular wall thickness and mass. Changes in left ventricular systolic function did not correlate significantly with changes in other clinical, electrocardiographic, or echocardiographic measurements. In six cases (two in group 1), in which amyloid infiltration of the heart was proved by myocardial biopsy or autopsy, the only echocardiographic abnormality when the patients were asymptomatic was a moderate increase in left or right ventricular wall thickness. We found that M-mode and two-dimensional echocardiographic examinations can substantiate progressive amyloid infiltration of the heart and are useful tools for the noninvasive serial assessment of patients with primary systemic amyloidosis.     

免疫球蛋白轻链型淀粉样变性的诊疗进展

免疫球蛋白轻链型淀粉样变性(AL)为最常见的系统性淀粉样变性,其特征为单克隆免疫球蛋白轻链的错误折叠引起的淀粉样蛋白的沉积.AL发病机制与多发性骨髓瘤(MM)相关,可继发于MM.目前,诊断延误仍然为影响AL疗效的最主要因素.因此,早期诊断及治疗对改善AL患者的预后具有重要意义.笔者拟就AL诊断、治疗及预后进行综述.     

Ten years' experience of an amyloid clinic--a clinicopathological survey

The aetiology, clinical course and affected organs were studied in 124 patients with acquired systemic amyloidosis and seven patients with organ-limited amyloid deposits. Seventy-five patients had reactive systemic AA amyloidosis, which was associated with rheumatic disease in 55 and with chronic infection in 13 cases. Forty-nine patients had systemic AL amyloidosis. Thirteen of these cases were associated with myelomatosis and 11 with non-malignant immunocyte dyscrasias. In 25 patients with systemic AL disease no immunocyte dyscrasia was identified. Renal involvement dominated the clinical course of both forms of systemic amyloidosis, and renal failure was the most common cause of death. Gastrointestinal disturbance and hepatosplenomegaly were found in both AA and AL disease, although differences were noted in the distribution of amyloid protein within rectal biopsies. Amyloid cardiomyopathy, neuropathy and macroglossia were present in patients with AL amyloidosis only. These clinical patterns were reflected by tissue distribution at necropsy in 67 patients.     

Recognition of congestive heart failure due to senile cardiac amyloidosis

Senile cardiac amyloidosis has been considered an incidental finding at autopsy in the elderly and of little clinical importance. Autopsy studies have shown that a subset of this group have large deposits of amyloid in their ventricles. Many of these patients had congestive heart failure antemortem. Senile cardiac amyloidosis, however, is rarely diagnosed antemortem and is often confused with primary systemic amyloidosis involving the myocardium. Using endomyocardial biopsy with newly developed immunohistochemical techniques, we have been able to recognize senile cardiac amyloidosis premortem. We have found that these patients have a longer survival than patients with primary systemic amyloidosis. In addition, senile cardiac amyloidosis occurs at a younger age than autopsy studies suggest. Recognition is important because these patients should not be given treatment reserved for the therapy of primary cardiac amyloidosis.     

Four-dimensional ultrasonography for dynamic bladder shape visualization and analysis during voiding.

OBJECTIVE: The purpose of this study was to describe initial applications of 4-dimensional ultrasonography (4DUS) for visualizing dynamic change in 3-dimensional (3D) bladder shape as well as for analyzing intravesical volume and diameters during voiding. METHODS: In 15 healthy volunteers and 5 patients with lower urinary tract symptoms, 4DUS images of the bladder during voiding were obtained by transabdominal 4DUS and compared with the outcome of uroflowmetry. Changes of intravesical volume as well as diameters in axial, coronal, and sagittal planes were measured and analyzed in comparison with uroflow data. RESULTS: Dynamic 3D visualization of the bladder shape was feasible in all 20 men. Multiplanar display of 4DUS showed dynamic 3D images of the bladder during voiding to be simultaneously visualized in the axial, coronal, and sagittal planes. The change and decrease rate in intravesical volume calculated by 4DUS data had significant correlation with the average flow rate (P = .02) and the maximum flow rate (P = .04), respectively. Among the 3 diameters, the change of coronal diameter was significantly most correlated with change of the intravesical volume (P < .0001). The change in coronal diameter, which was observed in patients with urinary disturbance, had a significant difference compared with those observed in control subjects (P = .01). CONCLUSIONS: Monitoring of voiding with 4DUS was feasible in healthy men and patients with lower urinary tract symptoms. Four-dimensional ultrasonography has the potential to be a novel noninvasive urodynamic modality to visualize dynamically the lower urinary tract during voiding and to improve pathophysiologic understanding of voiding.     

检测骨髓异常浆细胞有助于诊断原发性系统性轻链淀粉样变性

原发性系统性轻链淀粉样变性(AL)是系统性淀粉样变性疾病中最常见的类型,最近已明确AL是异常浆细胞导致的恶性肿瘤。这些浆细胞产生过量的免疫球蛋白轻链,形成具有蛋白质毒性的纤维状淀粉样物,通过异常折叠和沉积于多种组织器官,引起多脏器损害。AL诊断较困难,以往主要通过活检组织的刚果红染色。现在使用流式细胞术可以通过患者骨髓浆细胞的免疫球蛋白轻链限制性及异常表型特征检测异常浆细胞克隆,有助于早期确诊AL,并作为诊断AL后临床疗效监测的重要指标。本文就AL的诊断和分型、临床特点、骨髓浆细胞免疫表型的流式细胞术检测,异常浆细胞免疫球蛋白轻链限制性和表型特点等作一简要的综述。     

Autonomic nerve disorders in generalized amyloidosis]

Various autonomic disturbances are usually seen in systemic amyloidosis with polyneuropathy, especially in familial amyloid polyneuropathy (FAP). In this paper we summarized the clinicopathological features of these autonomic symptoms. Orthostatic hypotension and bowel dysfunctions are two major autonomic manifestations of FAP, and at autopsy severe deposition of amyloid is observed in an extensive area of peripheral autonomic nervous system including sympathetic ganglia. Remarkable depletion of the extrinsic nerves with relative preservation of the intrinsic nerves is a characteristic finding in the gastrointestinal tract of the patients with FAP, and this abnormal innervation may produce the peculiar bowel disorders. Oral administration of L-threo-3,4-dihydroxyphenylserine, a precursor of noradrenaline, is effective for the treatment of these autonomic symptoms of FAP patients.     

Discrimination of bladder disorders in female lower urinary tract symptoms on ultrasonographic cystourethrography.

OBJECTIVE: To evaluate morphologic features of bladder disorders in female lower urinary tract symptoms using ultrasonographic cystourethrography and to elucidate the anatomic association of these morphologic characteristics. METHODS: Ultrasonographic cystourethrography was performed in 1049 women with lower urinary tract symptoms and 1 single urodynamic diagnosis, including 764 patients with genuine stress incontinence, 190 with detrusor instability, and 95 with a hypersensitive bladder. Thirty-six women with no lower urinary tract symptoms served as control subjects. Ultrasonographic assessment included measurement of the bladder neck position at rest and during stress and observation of the development of bladder neck funneling and cystocele during the Valsalva maneuver. RESULTS: Hypersensitive bladder and control groups had a significantly higher bladder neck position at rest and during stress, a lesser rotational angle of the bladder neck, a lower prevalence of bladder neck funneling and cystocele formation, and lesser mean bladder wall thickness than the other diagnostic groups. In the study groups, age, parity, and menopause may have effects on the cystourethrographic parameters except rotational angle and funneling of the bladder neck. With control of the confounding factors, bladder wall thickness at the trigone and dome was negatively correlated with the resting bladder neck angle (P = .006 and 0.019, respectively). Bladder wall thickness at the dome was positively associated with the rotational angle of the bladder neck (P = .022). Funneling of the bladder neck and development of cystocele during stress were positively associated with the resting and straining bladder neck angles as well as the rotational angle of the bladder neck. CONCLUSIONS: Ultrasonographic manifestation of a hypersensitive bladder is significantly different from that of genuine stress incontinence and detrusor instability.     

Imaging assessment of uncomplicated bladder outflow obstruction

To assess the impact of the use of plain X-ray films and ultrasound examinations on clinical decision-making in patients referred with symptoms of bladder outflow obstruction. Patients with symptoms of bladder outflow obstruction were recruited prospectively. After clinical assessment they underwent standard investigations of plain X-ray of the kidneys, ureters and bladder, and upper and lower urinary tract ultrasound. A management decision was made on the basis of all results. These decisions were then reviewed with specific reference to radiological findings to assess the role of imaging in the decision-making process. A total of 320 men were recruited for the study. X-ray of the kidneys, ureters and bladder detected 10 upper tract calculi, none of which has required active intervention to date. Four bladder calculi were detected. Two of these were also seen on ultrasound scan: one was small and insignificant, the other had caused microscopic haematuria, necessitating cystoscopy regardless of the X-ray findings. Upper tract ultrasound revealed abnormalities and anatomical variants which did not affect management. Four patients had upper tract dilatation but these had already had surgery planned on the basis of other investigations, including residual urine volume determination by lower tract ultrasound. Lower urinary tract ultrasound should be the only routine imaging used in the initial assessment of patients with bladder outflow obstruction, with consequent implications of reduced patient stress and reduced investigation cost.     

Clinical significance of histopathologic patterns of cardiac amyloidosis

Cardiac amyloidosis may be asymptomatic or an important cause of progressive heart failure and refractory arrhythmia. To identify the morphologic markers of clinically significant cardiac amyloidosis, we analyzed the hearts of 47 patients with autopsy-proven cardiac amyloidosis (21 with primary amyloidosis [AL] and 26 with senile cardiac amyloidosis [SCA]) histologically for the extent and pattern of amyloid deposits. The extent of amyloid deposition was graded 1 through 4, corresponding with less than 10%, 10 to 25%, 26 to 50%, and more than 50% histologic involvement of the myocardium, respectively. The pattern of deposits was classified as nodular, perifiber, or mixed type, and the presence or absence of vascular involvement was determined. The hearts with primary amyloidosis showed predominantly high-grade deposits (76% grades 3 and 4), a perifiber (65%) or mixed (30%) pattern of deposits, and frequent (90%) vascular involvement. The hearts with senile cardiac amyloidosis tended to have low-grade deposits (62% grades 1 and 2), a nodular pattern (92%) of deposits, and infrequent (4%) vascular involvement. Clinically significant cardiac amyloidosis was associated with grade 2 or greater amyloid deposits in the heart and with involvement of intramyocardial arterioles.     

Measurements of complement factor H-related protein (BTA-TRAK assay) and nuclear matrix protein (NMP22 assay)--useful diagnostic tools in the diagnosis of urinary bladder cancer?

Between 1997 and 2000 we investigated in a prospective study the voided urine samples of all consecutive patients undergoing cystoscopy independent from their clinical background (n = 705) with the BTA-TRAK assay (Bard Diagnostics, Redmont, USA) detecting a complement factor H-related protein (CFHrP) and the NMP22 assay (Matritech, Newton, USA) measuring a nuclear matrix protein, which is supposed to be specific for bladder cancer. The individuals were divided into three groups concerning the clinical background: 233 patients had urological diseases, 268 patients had urinary bladder cancer and 150 patients had other urological malignancies. Based on the clinical findings we compared our results with well established diagnostic methods for urinary bladder cancer such as cytology and the detection of hematuria. In addition, we investigated urine samples from 30 healthy individuals and 24 patients with urinary tract infection without performing cystoscopy. Following the recommendations of the European Group on Tumor Markers we used 95% specificity for benign urological diseases and urinary tract infections, which resulted in a sensitivity of 17% for active bladder cancer for the BTA-TRAK assay and 31% for NMP22. We compared these results with the detection of hematuria (specificity: 72%) and cytology, which had a sensitivity of 64% and 89%, respectively. Subsequently, we calculated sensitivity and specificity for the detection of relapse of the disease. Again using 95% specificity, in this case for patients with no evidence of disease (NED), in patients with recurrent disease the BTA-TRAK assay showed 8% sensitivity as compared to 12% for the NMP22 assay. Due to an insufficient specificity and sensitivity, both tests can neither be clinically useful in screening of high risk patients, nor in primary diagnosis of bladder cancer. They cannot replace neither cystoscopy nor cytology. In the follow-up care more investigations may be necessary to prove the benefit of existing diagnostic strategies for the discrimination between active and inactive bladder cancer.     

Rest-redistribution thallium-201 myocardial scintigraphic study in cardiac amyloidosis

Background: Histopathological study in amyloid heart demonstrates that myocyte destructed by the extracellular deposition of amyloid protein together with viable myocyte is present. We hypothesized that rapid thallium washout may be found in amyloid heart as in regions which have a mixture of viable myocyte and scar tissue in patients with myocardial infarction. Thus, the purpose of this study was to evaluate the extent and severity of myocardial damage due to amyloid deposits using the washout rate of the tracer on rest-redistribution thallium-201 (²⁰¹Tl) myocardial scans in cardiac amyloidosis patients. Methods: Rest-redistribution ²⁰¹Tl myocardial scintigraphy was performed in 5 patients with biopsy-proved systemic amyloidosis with cardiac involvement (amyloidosis group). The initial and delayed images were obtained 15?min and 4?h, respectively, after intravenous injection of the tracer of 111?MBq. Washout rate of the tracer was calculated. Twelve patients with no apparent heart disease served as controls (control group). Results: Mean washout rate of the whole heart was higher in the amyloidosis group than in the control group (56 ± 9% vs 36 ± 6%, p < 0.001). Particularly, 4 of the 5 patients in the amyloidosis group presented a very high rate of thallium clearance which ranged from 57 to 61%, and died in less than a year. In the remaining 1 patient who had a normal washout rate of the tracer in the first study, it changed from 40 to 53% during the 5-year follow-up period. Conclusions: Washout rate in the setting of rest and delayed ²⁰¹Tl images may represent the severity of amyloid depositions in the myocardium and may provide prognostic information.     

Tracheobronchial amyloidosis

OBJECTIVE: To evaluate the presentation and clinical course of patients with tracheobronchial amyloidosis. PATIENTS AND METHODS: We retrospectively reviewed the records of all patients with biopsy-proven tracheobronchial amyloidosis who were evaluated at the Mayo Clinic in Rochester, Minn, between 1973 and 1999. All relevant information, such as clinical, historical, demographic, laboratory, and histological data, was examined. RESULTS: Tracheobronchial amyloidosis was diagnosed in 17 patients (9 women and 8 men), with a mean age of 56.6 years. The most common symptoms at presentation were dyspnea, cough, hemoptysis, and hoarseness. None of the 14 patients who underwent investigation for systemic amyloidosis had any evidence of disease outside the tracheobronchial system except for a man in whom multiple myeloma had been diagnosed 3 years before the development of respiratory disease. Treatment of tracheobronchial amyloidosis consisted of laser or forceps resection, external radiation, systemic therapy, or observation. Two patients died of complications directly related to their disease. CONCLUSIONS: Patients presenting with tracheobronchial amyloidosis have symptoms similar to those caused by various airway disorders. Tracheobronchial amyloidosis is not typically associated with systemic amyloidosis or pulmonary parenchymal involvement. It often recurs and despite repeated attempts with bronchoscopic techniques, airway compromise remains a major problem.