Localized Gastric Amyloidosis that Displayed Morphological Changes over 10 Years of Observation

We herein report an extremely rare case of localized gastric amyloidosis (LGA) with morphological changes during the follow-up. A 71-year-old woman who had a depressed lesion with central elevation in the gastric lower body was diagnosed with LGA. Esophagogastroduodenoscopy at 10 years after the initial examination showed that the lesion had grown and changed morphologically, exhibiting a submucosal tumor-like appearance. Since the lesion was confined to the submucosa, the patient underwent endoscopic submucosal dissection. The final pathological diagnosis was amyloid light-chain (AL)-type LGA. This case may provide useful information regarding the natural history of AL-type LGA.     

Cardiac Amyloidosis: An Updated Review With Emphasis on Diagnosis and Future Directions

Cardiac amyloidosis occurs because of abnormal protein (amyloid) deposition in the cardiac tissue. Even with advanced diagnostic techniques and treatments, the prognosis of amyloidosis remains poor. The diagnosis of cardiac amyloidosis particularly needs to be in the differential in patients presenting with heart failure with preserved ejection fraction. This entity remains underdiagnosed due to lack of suspicion on the part of many clinicians. Involvement of cardiac tissue is the utmost determinant factor for available treatment options and prognosis. Many cases of cardiac amyloidosis usually remain undiagnosed or diagnosed only in advanced stages when treatment options are limited and associated with poor survival. Hence, early recognition of cardiac amyloidosis is indispensable in halting the disease process before irreversible changes occur. The purpose of this review is to summarize the recent updates in the evaluation and management of cardiac amyloidosis and to discuss potential future treatments options.     

Idiopathic AL amyloidosis and biclonal paraproteinemia: a case report and review of the literature.

A case of 79 year-old man suffering from nephrotic syndrome, infiltrative cardiomyopathy and sensitive neuropathy of the lower limbs, associated with biclonal gammopathy (IgG K and IgA A), is described. There was a history of non-insulin dependent diabetes mellitus and of two lung nodules considered as benign lesions on the basis of cytologic, hematologic and instrumental examination. A rectal biopsy positive for amyloid deposition (Congo red histology and immunofluorescence study) led to the diagnosis of AL amyloidosis. Considering that the patient did not fulfill diagnostic criteria for lymphoproliferative diaseases (myeloma, lymphoma or Waldenstr?m's macroglubulinemia), nor for secondary malignant paraproteinemia, a diagnosis of idiopathic AL amyloidosis with biclonal gammopathy was made. Very few cases of idiopathic AL amyloidosis with double component are reported in the literature. Our review suggests that idiopathic AL amyloidosis with biclonal gammopathy is similar to idiopathic AL amyloidosis with monoclonal paraproteinemia in terms of clinical features, response to therapy and prognosis. Further studies, however, are necessary to clarify the true incidence and the clinical features of idopathic AL amyloidosis associated with biclonal gammopathy.     

Renal involvement by AA amyloidosis in inclusion body myositis

Inclusion body myositis is currently considered a variant of adult inflammatory myopathies. Clinical course is insidious and besides typical proximal muscles disorder, extension to distal ones is found in up to 95% of cases. Mean survival ranges from 3 to 5 years. Infections are the first death cause, secondary to existing disability a few years after diagnosis. Chronic rheumatic diseases related amyloidosis has became the most frequent kind of reactive amyloidosis or AA amyloidosis. Clinical manifestations of AA amyloidosis mainly affect the kidney. We present the case of a woman with Inclusion body myositis and renal involvement by AA amyloidosis. In our review of literature we haven t found any article relating AA amyloidosis with idiopathic inflammatory myopathies of the adult, what would turn this case into the first ever reported. We can probably find the reason in the bad prognosis of this entity. So we propose making a renal biopsy to all those patients with a long lasting rheumatologic disease and unexpected impaired renal function.     

Cardiovascular magnetic resonance imaging for amyloidosis: The state-of-the-art

Amyloidosis results from insoluble precursor proteins being deposited in the extracellular compartment. The prognosis of the disease is predominantly determined by cardiac involvement due to amyloid accumulation that contributes to cardiac dysfunction and disturbed conduction of cardiac electrical signals. The clinical and radiological manifestations of amyloidosis are often non-specific, making amyloidosis a diagnostic challenge both for clinicians and radiologists. Cardiovascular magnetic resonance imaging, including conventional sequences, late gadolinium enhancement, T1 mapping and determination of extracellular volume fraction is a multi-dimensional modality for the assessment and diagnosis of cardiac amyloidosis and, in addition, is an excellent tool for risk stratification and disease tracking.     

How to Identify Transthyretin Cardiac Amyloidosis at an Early Stage

Cardiac involvement of systemic amyloidosis is preferentially observed in patients with amyloid light chain amyloidosis or transthyretin amyloidosis (ATTR). Owing to the development of diagnostic modalities and changes in recognition by physicians, transthyretin cardiac amyloidosis (ATTR-CA) is now understood to be a more common cause of heart failure than previously thought. Recent progress in disease-modifying therapeutic interventions, such as transthyretin stabilizers, has resulted in ATTR-CA changing from an incurable disease to a curable disease. These interventions are particularly effective in patients with mild symptoms of heart failure, thus indicating that early detection and a precise diagnosis are important for improving the prognosis. In this review article, we summarize the recent reports of early screening of ATTR-CA and describe some important points regarding the making of a precise diagnosis, especially focusing on histological evaluations.     

胃黏膜幽门螺杆菌感染病理组织学专家共识

胃黏膜幽门螺杆菌（Helicobacter pylori， HP）感染是引发胃部疾病的主要危险因素之一，HP也被世界卫生组织等列为明确致癌物。目前临床常用的非侵入性法检测HP具有一定的限制性，如无法明确HP定植位置，也可能因其处于休眠期而漏诊或误诊。相较而言，病理学方法检测HP结果更为精准，可了解组织病变情况，并指导后续治疗与预后判断。组织学检测HP方法众多，不同地区、不同医院的病理医师在检测方法的选择上尚存在较大差异。因此，中华医学会消化内镜学分会病理学组根据我国实际情况制定此共识，旨在规范胃组织标本HP感染的病理诊断，为临床医师提供有关胃黏膜HP感染病理组织学的诊断治疗建议，以提高对疾病的认识和提升疾病治疗效果。     

Chronic diarrhea as the initial clinical manifestation of light-chain amyloidosis with cardiac involvement despite negative duodenal and rectal biopsies

Early and accurate diagnosis and a prompt initiation of treatment are critical for the prognosis of light-chain amyloidosis. The present article describes a case involving a 62-year-old patient who experienced unexplained, chronic diarrhea with negative duodenal and rectal biopsies. Serum immunofixation, a free light-chain assay, electrocardiography and echocardiography were performed after the patient developed syncope. The results of these diagnostic investigations showed characteristic signs of systemic amyloidosis. Cardiac and bone marrow biopsies confirmed the diagnosis of systemic light-chain amyloidosis. The chronic diarrhea was found to be due to an autonomic neuropathy of the enteric nervous system.     

Transthyretin cardiac amyloidosis: A treatable form of heart failure with a preserved ejection fraction

Cardiac amyloidosis (CA) is considered a rare disease with poor prognosis and limited therapeutic options. However, non-biopsy diagnostic modalities as well as emerging therapies are challenging this long-held belief. Radionuclide bone scintigraphy is increasingly being used in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). As such, it is expected that the number of patients diagnosed with ATTR-CA will continue to rise. Emerging therapies decrease the progressive morbidity and mortality associated with ATTR-CA. The importance of early recognition of ATTR-CA is imperative as prompt initiation of these novel agents is essential to maximize their therapeutic potential. Herein, we outline the current approach to diagnosis of ATTR-CA and review the therapeutic management of the disease.     

功能性胃肠病罗马Ⅲ诊断标准的临床实践和难点

罗马Ⅲ诊断标准已影响临床医师对功能性胃肠病(FGIDs)的诊断水准、流行病学调查和循证医学发展。本文就着重讨论FGIDs诊断标准的临床实践,包括基于症状的诊断、重叠症、共病现象、精神心理障碍、老年FGIDs、胃肠功能检查及其对治疗的指导意义等,并提出相应难点和应对措施,旨在帮助该诊断标准更合理地应用于临床实践。     

Systemic amyloidosis with gastrointestinal involvement: Diagnosis from endoscopic and histological views

Amyloid tends to deposit in the gastrointestinal tract, which, being easily accessible, is often the target organ for a pathological diagnostic examination. Although a mucosal biopsy is necessary for a definitive diagnosis and several studies have reported positive results for each possible biopsy site, there remain many unclear features in various aspects. This review focuses on the current literature to determine a better understanding of the diagnosis from endoscopic and histological views in patients with systemic amyloidosis with gastrointestinal involvement. A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed. Endoscopic findings vary based on the organ and the depositing amyloids. A fine granular appearance or polypoid protrusions are likely to occur in the duodenum. AL, Aβ2M, and ATTR amyloids are likely to deposit submucosally, while AA amyloid is easily deposited in the superficial layer of the mucous membrane. Furthermore, it is necessary to consider the collection of biopsy specimens from the duodenum, which has high positive biopsy rates. However, the difference in the positive biopsy rates depends on whether endoscopic findings are available or whether the appropriate number has not been fully elucidated. A duodenal biopsy is strongly recommended to confirm the deposition of amyloid in patients with systemic amyloidosis having gastrointestinal involvement. Because amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are required; gastroenterologists and endoscopists play important roles.     

继发性淀粉样变的临床特点

目的：研究继发性淀粉样变的临床特点、治疗与预后。方法：对诊为继发性淀粉样变的全部住院病例进行回顾性临床分析。结果：在8例继发性淀粉样变病人中，其原发病分别为结缔组织病4例，多发性骨髓瘤3例，慢性乙型肝炎1例。由结缔组织病至继发淀粉样变平均6.2年，肾脏为其主要累及器官，表现为蛋白尿（4例），1例发生肾功能衰竭，以免疫抑制剂及/或激素治疗后，患者平均生存期长于10年。多发性骨髓瘤继发淀粉样变的时间较短，以舌组织及心肌受累为主，化疗效果差，病人的生存期平均不超过2年。而继发于慢性肝炎后的淀粉样变主要表现为胸腔积液与肝脾大，病情相对平缓。结论：淀粉样变可以继发于结缔组织病、多发性骨髓瘤或慢性炎性疾病，他们的起病时间、受累脏器以及临床表现差异很大，继发于多发性骨髓瘤的淀粉样变预后差，但结缔组织病继发的淀粉样变经积极有效的治疗可以明显改善预后。     

Isolated Cardiac Involvement in Primary Amyloidosis: Presenting as Sick Sinus Syndrome and Heart Failure

Cardiac amyloidosis is an infiltrative cardiomyopathy with a grave prognosis. Its clinical manifestations include restrictive cardiomyopathy, diastolic heart failure, conduction defects, and arrhythmias. Isolated cardiac involvement and significant conduction disturbances are reported very infrequently. We report a rare case of isolated cardiac involvement in primary amyloidosis, in a 76-year-old man who initially presented with sick sinus syndrome that necessitated permanent pacemaker insertion. Subsequent symptoms of heart failure led to additional evaluation, including an endomyocardial biopsy that revealed primary cardiac amyloidosis. Medical therapy improved the patient''s symptoms, and he was discharged from the hospital in stable condition. In addition to discussing the patient''s case, we review the relevant medical literature.Key words: Amyloidosis/complications/drug therapy/pathology, cardiomyopathies/complications/pathology, heart failure/diagnosis/etiology, prognosis, treatment outcomeCardiac amyloidosis is an infiltrative cardiomyopathy caused by the deposition of proteinaceous material, called amyloid, in the extracellular space of the heart. Clinical manifestations can include restrictive cardiomyopathy, diastolic heart failure, conduction defects, and arrhythmias.¹ We describe a rare case of primary cardiac amyloidosis in an elderly man who initially presented with sick sinus syndrome that necessitated permanent pacemaker insertion. Subsequent symptoms of heart failure prompted additional evaluation that established a diagnosis of primary cardiac amyloidosis.     

Angina with a normal coronary angiogram caused by amyloidosis

A case of severe intractable angina pectoris with normal angiography is presented. Following video assisted thoracic sympathectomy the patient died of heart failure. Microvascular cardiac amyloidosis was diagnosed at the postmortem examination. This report alerts clinicians to this possible diagnosis when treating patients with severe angina when no cause is found and discusses the poor prognosis in such cases.     

Globular amyloidosis of the colon

Gastrointestinal involvement is frequent in systemic amyloidosis. However, amyloidosis can rarely be confined to the gastrointestinal tract or appear as a tumour mass. There have been few reports describing amyloid globular deposits in a variety of locations, as opposed to the usual linear ones. We herein report a rare case of globular amyloidosis involving the large bowel, which to the best of our knowledge is the second reported in the world literature.A 74-year-old man consulted on anaemia. Endoscopy showed ulcerative lesions in the left colon, which were biopsied and diagnosed as ischemic colitis. Under light microscopy, we found globular discrete deposits in the lamina propria which were Congo red-positive and resistant to permanganate digestion. Histopathological diagnosis was globular amyloidosis with AL deposits. The patient underwent further studies, including a haematologic evaluation that discarded systemic involvement.Globular amyloidosis seems to be a rare morphologic type of amyloidosis, but not a distinct entity. Its etiology, pathogenesis and relationship with patient prognosis and disease severity remain largely unknown. When amyloid deposits are confined to the gastrointestinal tract, systemic therapy can be avoided and patients should only be followed periodically. Immunohistochemical classification and clinical correlation are essential to rule out systemic amyloidosis.     

Systemic amyloidosis: a clinical challenge

This study reports a case of an 82-year-old white woman with a history of congestive heart failure refractory to diuretic therapy who was found to have systemic amyloidosis, confirmed by a rectal biopsy. Cardiac involvement by amyloid should be considered in the differential diagnosis of any patient with heart failure with preserved ventricular systolic function, who does not have evidence of ischaemic heart disease or hypertension. However, the rarity of this disease and the various involvement of different organs and tissues are often responsible for missed or delayed diagnosis. Systemic amyloidosis is a life-threatening disease but an early diagnosis may modify its course; therefore it is important to maintain a high clinical suspicion and to increase the awareness of this overlooked condition among clinicians.     

Nonfunctioning benign cardiac pheochromocytoma

Purpose   Nonfunctioning benign cardiac pheochromocytoma is one of the rarest tumors and only a few cases have been described before. We present a rare case of nonfunctioning benign cardiac pheochromocytoma and a review of the literature with special emphasis on diagnosis and treatment. Methods  Different from the other cardiac pheochromocytomas, its symptoms and signs are so nonspecific that it is easy to make a misdiagnosis or missed diagnosis. One patient with nonfunctioning benign cardiac pheochromocytoma was treated surgically and relevant cases data were collected. Clinical features, diagnosis and treatment of pheochromocytoma were discussed. Results  The presented case was cured by surgery. The prognosis for patients of benign cardiac pheochromocytomas was excellent, but for those of malignant ones was very poor. Conclusion  Reviewing the few reported cases, most nonfunctioning benign cardiac pheochromocytomas can be cured completely by operation with good prognosis.     

Systemic amyloidosis from A (AA) to T (ATTR): a review

Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and nonspecific resulting in diagnostic delay. The field of amyloidosis has seen significant improvements over the past decade in diagnostic accuracy, prognosis prediction and management. The advent of mass spectrometry-based shotgun proteomics has revolutionized amyloid typing and has led to the discovery of new amyloid types. Accurate typing of the precursor protein is of paramount importance as the type dictates a specific management approach. In this article, we review each type of systemic amyloidosis to provide the practitioner with practical tools to improve diagnosis and management of these rare disorders.     

Pseudoachalasia and secondary amyloidosis in a patient with rheumatoid arthritis

Rheumatic diseases cover a wide spectrum of clinical syndromes and frequently present with gastrointestinal alterations. Systemic amyloidosis is associated with infectious diseases or chronic inflammatory processes such as rheumatoid arthritis and it can also affect the gastrointestinal tract. Although esophageal involvement is difficult to quantify because its course is frequently asymptomatic, systemic amyloidosis is recognized as a cause of motor disorders of the esophagus. Typical manometric patterns, including achalasia, are usually absent. Esophageal involvement due to amyloid deposits usually corresponds to primary amyloidosis as only a few cases of secondary esophageal deposits (type AA) have been described. We describe a new case of this exceptional association that first presented as dysphagia in a patient with rheumatoid arthritis. The initial suspicion of pseudoachalasia led to the definitive diagnosis of secondary amyloidosis.     

Coil embolization of asymptomatic left gastric artery aneurysm: Case report and literature review

Patients with visceral artery aneurysms are rare, and the reported incidence of left gastric aneurysm (LGA) is only 4%. At present, although there is little knowledge about such disease, it is generally believed that appropriate treatment should be planned to prevent some dangerous aneurysms from rupturing. We introduced a case of 83-year-old patient with LGA who underwent endovascular aneurysm repair. The 6-month follow-up computed tomography angiography showed complete thrombosis in the aneurysm lumen. In addition, to insight the management strategy on LGAs deeply, a literature review concerning this entity published in recent 35 years was performed.