Figure - available from: Case Reports in Hematology
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Serum protein electrophoresis before (a) and after (b) therapy. After therapy, there was a reduction of the monoclonal component (1).
Source publication
Primary systemic amyloidosis is not easily diagnosed. The immunoglobulin deposits are usually localized in the kidney, heart, and liver. We describe an unusual case of a patient suffering from a pericardial amyloidoma with internal calcifications and air bubbles that compressed the right ventricle and shifted the heart to the left. Since the patien...
Citations
... Multiple myeloma (MM) is a malignant proliferation of clonal plasma cells (PCs) that expand in the bone marrow (BM), with ensuing induction of focal skeletal lesions and osteoporosis. Clinical presentation includes myeloma bone disease, anemia, renal insufficiency, hypercalcemia [1,2], higher infection rates [3,4] and secondary life-threatening complications [5][6][7][8]. MM remains an incurable disease, despite conventional therapies [9,10] and considerable improvements in novel therapeutic approaches [11]. The MM cell within the bone niche has direct and indirect contact with skeletal cells modulating bone resorption and regeneration [12]. ...
Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic outcomes. Nevertheless, some subgroups of patients include those with particularly unfavorable prognoses. Biological stratification can be used to categorize patient-, disease- or therapy-related factors, or alternatively, these biological determinants can be included in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current knowledge enforce a systematic and comprehensive bench-to-bedside approach. Given the increasing role of cancer stem cells (CSCs) in better characterizing the pathogenesis of solid and hematological malignancies, disease relapse, and drug resistance, identifying and describing CSCs is of paramount importance in the management of MM. Even though the function of CSCs is well-known in other cancer types, their role in MM remains elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow micro milieu. These data are particularly interesting for clinicians facing unmet medical needs while designing novel treatment approaches for MM.
... Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells (PCs) accumulating and disseminating in the bone marrow (BM) with ensuing induction of focal skeletal lesions and osteoporosis driving myeloma bone disease, anemia, renal insufficiency, hypercalcemia [72], higher infection rates [73][74][75], and secondary life-threatening complications [76][77][78]. MM represents an ideal model of colonization and interaction of tumor cells in the bone microenvironment [79][80][81], where the immune-milieu [82,83] and aberrant angiogenesis shape a permissive ecosystem, supporting disease progression via a plethora of autocrine [84,85] and paracrine loops [86,87]. ...
Simple Summary
A clinical decision and study design investigating the level and extent of angiogenesis modulation aimed at vascular normalization without rendering tissues hypoxic is key and represents an unmet medical need. Specifically, determining the active concentration and optimal times of the administration of antiangiogenetic drugs is crucial to inhibit the growth of any microscopic residual tumor after surgical resection and in the pre-malignant and smolder neoplastic state. This review uncovers the pre-clinical translational insights crucial to overcome the caveats faced so far while employing anti-angiogenesis. This literature revision also explores how abnormalities in the tumor endothelium harm the crosstalk with an effective immune cell response, envisioning a novel combination with other anti-cancer drugs and immunomodulatory agents. These insights hold vast potential to both repress tumorigenesis and unleash an effective immune response.
Abstract
Cancer-associated neo vessels’ formation acts as a gatekeeper that orchestrates the entrance and egress of patrolling immune cells within the tumor milieu. This is achieved, in part, via the directed chemokines’ expression and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. The crosstalk between adaptive immune cells and the cancer endothelium is thus essential for tumor immune surveillance and the success of immune-based therapies that harness immune cells to kill tumor cells. This review will focus on the biology of the endothelium and will explore the vascular-specific molecular mediators that control the recruitment, retention, and trafficking of immune cells that are essential for effective antitumor immunity. The literature revision will also explore how abnormalities in the tumor endothelium impair crosstalk with adaptive immune cells and how targeting these abnormalities can improve the success of immune-based therapies for different malignancies, with a particular focus on the paradigmatic example represented by multiple myeloma. We also generated and provide two original bio-informatic analyses, in order to sketch the physiopathology underlying the endothelial–neoplastic interactions in an easier manner, feeding into a vicious cycle propagating disease progression and highlighting novel pathways that might be exploited therapeutically.
... Symptoms and signs are mostly non-specific, which is a further obstacle to making an early [10,11] diagnosis, complicated by the high prevalence of other cardiovascular diseases such as coronary heart disease, arrhythmias, and valvular heart diseases. In cases of a high clinical suspicion of a restrictive etiology of unexplained cardiomyopathy is essential. ...
Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, which can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted to our ward between 1981 and 2019. Among them, 54 patients (46.30% F/53.70% M, aged 63.95 ± 12.82) presented CA at baseline. In 53 patients, it was associated with a multiorgan involvement, while in one there was a primary myocardial deposition. As a control group, we enrolled 81 patients (49.30% F/50.70% M, aged 58.33 ± 15.65) who did not meet the criteria for CA. In 44/54 of patients CA was associated with AL, 5/54 with AA and 3/54 of patients with ATTR, and in 1/54 AL was related to hemodialysis and in 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/44) or IgD (2/44), while seven patients had a λ free light chain form. The 32 AL with complete Ig were 31 λ-chain and just one k-chain. CA patients presented normal BP (SBP 118.0 ± 8.4 mmHg; DBP 73.8 ± 4.9 mmHg), while those with nCA had an increased proteinuria (p = 0.02). TnI and NT-proBNP were significantly increased compared to nCA (p= 0.031 and p = 0.047, respectively). In CA patients we found an increased LDH compared to nCA (p = 0.0011). CA patients were also found to have an increased interventricular septum thickness compared to nCA (p = 0.002), a decreased Ejection Fraction % (p = 0.0018) and Doppler velocity E/e' ratio (p = 0.0095). Moreover, CA patients had an enhanced right atrium area (p = 0.0179), right ventricle basal diameter (p = 0.0112) and wall thickness (p = 0.0471) compared to nCA, and an increased inferior cava vein diameter (p = 0.0495) as well. TAPSE was the method chosen to evaluate systolic function of the right heart. In CA subjects very poor TAPSE levels were found compared to nCA patients (p = 0.0495). Additionally, we found a significant positive correlation between TAPSE and lymphocyte count (r = 0.47; p = 0.031) as well as Gamma globulins (r = 0.43, p = 0.033), Monoclonal components (r = 0.72; p = 0.047) and IgG values (r = 0.62, p = 0.018). Conversely, a significant negative correlation with LDH (r = −0.57, p = 0.005), IVS (r = −0.51, p = 0.008) and diastolic function evaluated as E/e' (r = −0.60, p = 0.003) were verified. CA patients had very poor survival rates compared to controls (30 vs. 66 months in CA vs. nCA, respectively, p = 0.15). Mean survival of CA individuals was worse also when stratified according to NT-proBNP levels, using 2500 pg/mL as class boundary (174 vs. 5.5 months, for patients with lower vs. higher values than the median, respectively p = 0.013). In much the same way, a decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18 mm, p = 0.0186). Finally, our data highlight the potential prognostic and predictive value of right heart alterations characterizing amyloidosis, as a novel clinical parameter correlated to increased LDH and immunoglobulins levels. Overall, we confirm the clinical relevance of cardiac involvement suggests that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis.
... 1 It has also been reported to occur on serous membranes such as the pericardium. 3 There have also been case reports of plasmacytomas that can occur at the same location as in our patient, the atrioventricular groove. 4,5 Plasmacytomas have also been associated with neuropathy. ...
The final version of the manuscript is published on "Life" In October 2020
https://doi.org/10.3390/life10100247
https://www.researchgate.net/publication/344727443_Right_Heart_Changes_Impact_on_Clinical_Phenotype_of_Amyloid_Cardiac_Involvement_A_Single_Centre_Study
