An Unusual Case of Hepatic Tumor

A case is reported of a large hepatic tumor in a patient aged 71. Preoperative diagnostic techniques, including echography, CT and angiography, did not provide sufficient criteria for a precise diagnosis. The mass was removed with an extended right hepatectomy with no particular physiopathological consequences. Histological analysis revealed that this was a metastasis from a melonoma of the choroid, operated on 17 years previously

Central Nervous System Myeloma and New Drugs: Can we Begin the Fight?

Editoria

A case of bone lesion in a patient with relapsed chronic lymphocytic leukemia and review of the literature

Skeletal involvement in CLL is very rare. We present a case of ileum bone lesion during in a patient receiving 5th line of therapy. Despite radiotherapy and salvage therapies, subsequent bone lesions led to a fatal outcome. Further studies on the mechanism by which bone disease develops are currently needed

The effect of zoledronic acid on serum osteoprotegerin in early stage multiple myeloma

We evaluated the effect of zoledronic acid (ZA) on serum levels of osteoprotegerin (OPG) and the ligand for receptor activator of nuclear factor kappaB (RANKL) in patients with smoldering myeloma. In treated subjects we found an increase of OPG accounting for an effect of ZA on osteoblast and/or bone marrow stromal cells together with the direct effect on osteoclasts

Tumor-Associated Macrophages in Multiple Myeloma: Key Role in Disease Biology and Potential Therapeutic Implications

Multiple myeloma (MM) is characterized by multiple relapse and, despite the introduction of novel therapies, the disease becomes ultimately drug-resistant. The tumor microenvironment (TME) within the bone marrow niche includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages, with a complex cross-talk between these cells and the MM tumor cells. Tumor-associated macrophages (TAM) have an important role in the MM pathogenesis, since they could promote plasma cells proliferation and angiogenesis, further supporting MM immune evasion and progression. TAM are polarized towards M1 (classically activated, antitumor activity) and M2 (alternatively activated, pro-tumor activity) subtypes. Many studies demonstrated a correlation between TAM, disease progression, drug-resistance and reduced survival in lymphoproliferative neoplasms, including MM. MM plasma cells in vitro could favor an M2 TAM polarization. Moreover, a possible correlation between the pro-tumor effect of M2 TAM and a reduced sensitivity to proteasome inhibitors and immunomodulatory drugs was hypothesized. Several clinical studies confirmed CD68/CD163 double-positive M2 TAM were associated with increased microvessel density, chemoresistance and reduced survival, independently of the MM stage. This review provided an overview of the biology and clinical relevance of TAM in MM, as well as a comprehensive evaluation of a potential TAM-targeted immunotherapy

Multiple Myeloma Manifesting as a Fluctuating Sixth Nerve Palsy

We report a case of multiple myeloma that presented as a fluctuating sixth cranial nerve palsy in the absence of widespread signs of systemic disease. A 63-year-old woman presented with horizontal diplopia of two weeks duration that subjectively changed over time. Ocular examination showed a fluctuating sixth nerve palsy. A computed tomography (CT) scan of the brain showed multiple, enhancing, soft tissue, mass-like lesions involving the left cavernous sinus and the apex of both petrous bones. Based on bone marrow biopsy and hematologic findings, she was diagnosed with multiple myeloma. Multiple myeloma may be included in the differential diagnosis of a fluctuating sixth nerve palsy, and although ophthalmic signs are rare and generally occur late in the course of multiple myeloma, they can still be its first signs

Drug resistance and minimal residual disease in multiple myeloma

Great progress has been made in improving survival in multiple myeloma (MM) patients over the last 30 years. New drugs have been introduced and complete responses are frequently seen. However, the majority of MM patients do experience a relapse at a variable time after treatment, and ultimately the disease becomes drug-resistant following therapies. Recently, minimal residual disease (MRD) detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response. MRD can be considered as a surrogate for both progression-free and overall survival. In this perspective, the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals. The present review gives an overview of drug resistance in MM, i.e., mutation of β5 subunit of the proteasome; upregulation of pumps of efflux; heat shock protein induction for proteasome inhibitors; downregulation of CRBN expression; deregulation of IRF4 expression; mutation of CRBN, IKZF1, and IKZF3 for immunomodulatory drugs and decreased target expression; complement protein increase; sBCMA increase; and BCMA down expression for monoclonal antibodies. Multicolor flow cytometry, or next-generation flow, and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5. Sustained MRD negativity is related to prolonged survival, and it is evaluated in all recent clinical trials as a surrogate of drug efficacy

Anti-BCMA novel therapies for multiple myeloma

Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals; however, the prognosis remains poor. The BCMA antigen is highly expressed in myeloma cells, thus representing a target for novel therapies. Several agents that target BCMA through different mechanisms, including bispecific T cell engagers drug conjugated to antibody and CAR-T cells, are now available or under development. Immunotherapies targeting BCMA have shown good results in efficacy and safety in multiple myeloma patients previously treated with several lines of therapy. This review will discuss the recent development of anti-BCMA targeted treatments in myeloma, with a special focus on currently available agents

Renal Stone Formation in Patients with Inflammatory Bowel Disease

Kidney stones are more common in patients with inflammatory bowel disease (IBD) than in the general population. The main lithogenetic risk factors were evaluated in patients affected by Crohn\u27s disease and ulcerative colitis. Our results show the presence of several factors, besides hyperoxaluria, in patients with IBD although their behaviour appears different in Crohn\u27s disease and ulcerative colitis at pre- and post-operative stages. Before surgery in patients with Crohn\u27s disease we found a decreased citrate (p \u3c 0.001) and magnesium (p \u3c 0.005) excretion together with a low urinary volume (p \u3c 0.001) and pH (p \u3c 0.005). After surgery patients with Crohn\u27s disease showed a further reduction of magnesium and citrate. Patients with ulcerative colitis before surgery showed a reduced citrate excretion (p \u3c 0.05) and a more acidic pH (p \u3c 0.05) than healthy subjects. Surgical treatment of proctocolectomy with ileal pouch-anal anastomosis seems to increase the risk of stone formation; in fact, after surgery we observed a relevant decrease of urinary volume (p \u3c 0.001), pH (p \u3c 0.0001) and urinary excretion of citrate (p \u3c0.0001) as well as magnesium (p \u3c 0.005). Patients with IBD seem to be at greater risk of stone formation than patients with idiopathic calcium lithiasis; in fact, they show a lower excretion of citrate (p \u3c 0.001) and magnesium (p \u3c 0.001) together with a low urinary pH (p \u3c 0.001) and volume (p \u3c 0.001). Urinary volume reduction is probably one of the major risk factors together with the decrease of small molecular weight inhibitors that is a constant finding in all patients with IBD

Venetoclax in association with decitabine as effective bridge to transplant in a case of relapsed early T‐cell lymphoblastic leukemia

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