Elbasvir/Grazoprevir combination therapy in a B-NHL patient with HCV genotype 1 infection.

Patients with indolent non-Hodgkin lymphomas (NHL) may often be followed up only with observation, reserving chemotherapy in case of spread. Patients with chronic HCV infection and B cell NHL frequently undergo regression of lymphoproliferative disease once HCV infection is eradicated by treatment. Interferon (IFN)-based therapy has been the treatment of choice for years, remaining unclear whether it is effective in B cell NHL directly or through HCV eradication, since IFN is effective in both HCV infection and B cell NHL. IFN therapy for HCV infection became obsolete with the advent of the well tolerated direct-acting antiviral agents (DAAs), whose excellent efficacy in treating patients with chronic HCV infection and B cell NHL has been recently highlighted. We treated a 53-year-old woman with chronic HCV infection and marginal zone lymphoma (MZL) with elbasvir plus grazoprevir in 2018, with complete remission and persisting excellent results: sustained virological response 24 weeks after treatment (SVR24). The exclusive role of HCV eradication in B cell NHL regression is also underlined.

Atypical haemolytic-uraemic syndrome in patient with metastatic colorectal cancer treated with fluorouracil and oxaliplatin: a case report and a review of literature.

Background. Thrombotic microangiopathies (TMA) are relatively rare but severe disorders characterised by non-immune haemolytic anaemia, thrombocytopaenia and organ failure. In patients with metastatic cancer, sporadic forms of TMA can be triggered by chemotherapeutic agents or can occur as complication of malignancy itself or of infections. Case report. Hereby, we report a case of a patient diagnosed with metastatic colorectal cancer who experienced an atypical haemolytic-uraemic syndrome (aHUS) during chemotherapy treatment with FOLFOX6 scheme. The use of eculizumab led to prompt recovery of laboratory parameters that was maintained despite treatment discontinuation due to appearance of pneumonia infectious. Additionally, genetic analyses revealed the presence in heterozygosis of CFH gene polymorphisms associated with aHUS. Conclusion. This case emphasises the importance of considering TMA as a possible diagnosis in patients with cancer presenting with haemolytic non-immune mediate anaemia and thrombocytopaenia associated with worsening of renal function. Prompt diagnosis is crucial for the requirement of its specific treatment that can impact on long-term outcome and prognosis.

Impact of the uremic milieu on the osteogenic potential of mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs), the precursors of osteoblasts during osteogenesis, play a role in the balance of bone formation and resorption, but their functioning in uremia has not been well defined. To study the effects of the uremic milieu on osteogenic properties, we applied an in vitro assay culturing hMSCs in osteogenic medium supplemented with serum from healthy donors and from uremic patients on hemodialysis. Compared to control, serum from uremic patients induces, in hMSC cultures, a modification of several key regulators of bone remodeling, in particular a reduction of the ratio Receptor Activator of Nuclear factor Kappa B Receptor (RANKL) over osteoprotegerin, indicating an adaptive response of the system to favor osteogenesis over osteoclastosis. However, the levels of osteopontin, osteocalcin, and collagen type I, are increased in cell medium, while BMP-2, and alizarin red staining were decreased, pointing to a reduction of bone formation favoring resorption. Selected uremic toxins, such as p-cresylsulfate, p-cresylglucuronide, parathyroid hormone, indoxyl sulfate, asymmetric dimethylarginine, homocysteine, were able to mimic some of the effects of whole serum from uremic patients. Serum from cinacalcet-treated patients antagonizes these effects. Hydrogen sulfide (H2S) donors as well as hemodialysis treatment are able to induce beneficial effects. In conclusion, bone modifications in uremia are influenced by the capability of the uremic milieu to alter hMSC osteogenic differentiation. Cinacalcet, H2S donors and a hemodialysis session can ameliorate the hampered calcium deposition.

Clinical significance of serum triple monoclonal components: a report of 6 cases and a review of the literature.

A serum multiple monoclonal component (MC) is very rare. We here report 6 patients with 3 MCs. The triple MC was detected in all of them by immunofixation. 2/6 patients did not present hematological or oncological associated disease, while in the remaining 4, Waldenström macroglobulinaemia (2 cases), Polycythemia Vera and non-Hodgkin lymphoma were diagnosed. Of the 49 global patients reported in the literature (6+43), 64.6% had a lymphoproliferative disorder and only in 3 cases there was no associated disease. Therefore, the detection of such laboratory evidence should propel physicians to a deeper investigation.

Absence of occult HCV infection in patients experiencing an immunodepression condition.

The aim of our study was to evaluate the presence of occult HCV infection in two settings of patients experiencing immunosuppression: patients with Human Immunodeficiency Virus (HIV) infection and those with onco-haematological disease. Sixty consecutive HIV-positive/anti-HCV-negative/HCV RNA-negative patients (HIV group) and 32 consecutive anti-HCV/HCV RNA negative patients with an onco-haematological disease first undergoing chemotherapy (Onco-haematological group) were enrolled. HCV-RNA was sought by real time RT-PCR in plasma and Peripheral Blood Mononuclear Cell (PBMC) samples obtained at enrolment and during follow-up, in the patients in the HIV group every three months and in those in the onco-haematological group at months 1 and 3 during chemotherapy and then every three months after treatment discontinuation. No plasma or PBMC sample collected at enrolment and during the follow-up in the HIV and onco-haematological groups was HCV RNA positive. The results of this study rule out the existence of occult HCV infection in patients with strong immunosuppression due to different conditions, HIV infection and onco-haematological diseases.

Secondary Extramedullary Plasmacytoma of the Duodenum: An Unusual Endoscopic Presentation.

We describe an unusual case (a 79-year-old woman) of secondary extramedullary plasmacytoma (EMP) involving the duodenum. While all the previously reported cases of duodenal involvement by EMP (namely 20 cases) were characterized by the presence of ulcerative masses or ischemic necrotic lesions, in our case EMP led to the unusual finding of several non-polypoid lesions with a depressed central area. The final diagnosis was multiple myeloma IgA lambda, stage II A, with secondary duodenal EMP. To our knowledge this is the first report showing duodenal involvement by EMP with the aspect of multiple non-polypoid lesions.

Transient reactivation of occult hepatitis B virus infection despite lamivudine prophylaxis in a patient treated for non-Hodgkin lymphoma.

A female patient with non-Hodgkin lymphoma who tested positive for surface antigen of the hepatitis B virus and negative for hepatitis B core antibody experienced a reactivation of occult HBV infection 20 months after rituximab discontinuation despite lamivudine prophylaxis covering the 4 months of rituximab administration and the subsequent 12 months.

Serum double monoclonal components and hematological malignancies: only a casual association? Review of 34 cases.

A double monoclonal component (MC) detected in the serum and/or urine represents a very rare occurrence (2-6% of monoclonal gammopathies). In this study, we report 34 patients with double serum MCs, focusing on the associated diseases. The diagnosis was made using high-resolution serum protein electrophoresis and immunofixation. Of the 1214 patients with monoclonal gammopathies, 49 had a double MC but only 34 (2.8%) were included in our study. A double MC was associated with hematological malignancies in 20/34 cases. Based on our experience, a double MC is more often associated with other diseases, especially an oncohematological one.

Primary extranodal non-Hodgkin's lymphoma of the vagina: a case report and a review of the literature.

Primary lymphoma of the female genital tract is very rare. We report the case of a 36-year-old woman who was referred to our hospital because of an indeterminate Pap smear test. The colposcopy showed a thickening of the posterior vaginal wall and various irregular ulcerated nodular lesions. Histological examination, immunohistochemistry and the staging procedures were conclusive of diffuse large B-cell lymphoma of the vagina, stage IEA. Complete remission was achieved after 6 cycles of immunopolychemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). No relapse has occurred during a follow-up of 71 months. Moreover, we reviewed the 62 previously reported cases of primary extranodal non-Hodgkin's lymphoma of the vagina, focusing on clinicopathological and therapeutic aspects, to better characterize this unusual disease.

Increased hepatitis C viral load and reactivation of liver disease in HCV RNA-positive patients with onco-haematological disease undergoing chemotherapy.

AIMS: To evaluate changes in Hepatitis C Virus (HCV) RNA both in plasma and Peripheral Blood Mononuclear Cells (PBMC) in onco-haematological patients. PATIENTS AND METHODS: 8 consecutive anti-HCV/HCV RNA-positive patients with onco-haematological diseases (5 with B-cell Non-Hodgkin Lymphoma and 3 with chronic lymphocytic leukaemia) were observed during chemotherapy and after its discontinuation. All were naïve to chemotherapy. HCV RNA was sought by Real Time Polymerase Chain Reaction in Light Cycler 1.5 in plasma and PBMC samples collected before, during and after chemotherapy. RESULTS: An increase in HCV RNA of at least 1.5 log IU/mL in plasma and 1.1 log IU/ml in PBMC was observed in all 7 patients undergoing Rituximab-based chemotherapy; these patients showed a hepatic flare after discontinuation, life-threatening in one with cirrhosis. Also the 8th patient had cirrhosis, but was treated with Rituximab-sparing chemotherapy and did not show any increase in HCV RNA or a hepatic flare. CONCLUSION: Rituximab-based chemotherapy favours an increase in HCV RNA in onco-haematological patients; this is followed by a hepatic flare, possibly immune-mediated and life threatening in cirrhotic patients.

An unusual cause of facial swelling: primary extranodal non-Hodgkin lymphoma of the masseter muscle.

Nearly 25% of non-Hodgkin lymphomas (NHLs) arise in extranodal locations. The involvement of soft tissue by NHL is uncommon. Primary extranodal NHL of the skeletal muscle is even rarer. The authors report a 49-year-old man with a 3-month history of progressive asymmetry of the face caused by swelling in the right cheek with paresthesia and burning. He underwent an excisional biopsy of the lesion. Histologic examination, immunohistochemistry and cytogenetic analysis were performed. The final diagnosis was primary large B-cell NHL of the masseter muscle, stage IEA. Rituximab-cyclophosphamide, epirubicin, vincristine and prednisone regimen was started. Restaging procedures after immunopolychemotherapy showed no evidence of disease. No relapse has occurred during a follow-up of 72 months. Although primary muscle lymphoma represents a rare entity, it can involve every muscle. Thus, when patients present with cheek swelling, physicians should always consider the possibility of lymphoma. The authors also reviewed the published literature concerning primary muscle lymphoma.

Chronic lymphocytic leukemia with associated lambda-light-chain and IgG lambda paraproteins simulating a biclonal gammopathy.

BACKGROUND: Monoclonal components (MCs) are frequently detected in the sera of patients with B-cell malignancies, by techniques that are getting more and more sensitive. Only few chronic lymphocytic leukemia (CLL) patients with multiple serum paraproteins are reported in the literature. METHODS: In this case report we present a 71-year-old woman with CLL and serum MCs. Immunofixation was performed on agarose film using anti-sera monospecific for the heavy and light chains of human immunoglobulins (anti-gamma, -alpha, -mu, -delta, -epsilon, -kappa, -lambda). Serum free light chains (FLCs) were quantified nephelometrically. Immunofluorescence analysis was performed using fluorochrome-conjugated goat antibodies specific for human mu, gamma or alpha immunoglobulin heavy chains and K or lamda light chains. RESULTS: Immunofixation revealed two different MCs (IgGlambda + lambda light-chains) in the serum and only one MC (lambda light chains) in concentrated urine. Serum lamda FLCs were 206 mg/L. The bone marrow aspiration and biopsy revealed a 38 % interstitial and nodular infiltration of mature small lymphocytes expressing IgG lambda surface immunoglobulins CD 19, CD20, CD5, and CD23, with negative BCL-1, t(11, 14) and cyclin D1. The plasma cells were less than 1%. Final diagnosis was CLL (Rai stage I) with IgG lamda plus lamda serum paraproteins. Three years later, the patient died because of myocardial infarction after a follow-up period with no need for CLL therapy. CONCLUSIONS: Our hypothesis is that the double MC may be the result of an unbalanced immunoglobulin chain synthesis by the leukemic B-cell clone, resulting in IgGlamda and excess of lambda FLCs.

Chin numbness: a symptom that should not be underestimated: a review of 12 cases.

The numb chin syndrome (NCS) is characterized by facial numbness along the distribution of the mental branch of the trigeminal nerve. Most cases of this syndrome that are not dental in origin have been associated with malignant tumors or diffuse metastatic disease, particularly with underlying lymphoproliferative diseases and breast cancer. NCS can appear together with other signs of neoplastic dissemination or constitute the presenting symptom of the disease. The appearance of this mental nerve neuropathy should be considered as a significant symptom for clinicians, and investigations to detect a possible cancer should be mandatory. We report 12 patients with the NCS as the presenting and isolated symptom of a generalized malignancy.

The ubiquitin-proteasome system contributes to the inflammatory injury in ischemic diabetic myocardium: the role of glycemic control.

BACKGROUND: Because the ubiquitin-proteasome pathway (UPS) is required for activation of nuclear factor kappa beta (NFkB), a transcription factor that regulates inflammatory genes, we evaluated the UPS activity, NFkB activation, and tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, in ischemic specimens of diabetic myocardium and relate them to the glycemic control (HbA(1c)), oxidative stress (nitrotyrosine, a modified amino acid produced by reactive O(2)), and cardiac outcome (echocardiographic parameters). Moreover, the role of UPS, NFkB, and TNF-alpha in the cardiac tissue injury of acute ischemia/reperfusion (I/R) was evaluated in streptozotocin (STZ)-hyperglycemic rats. Finally, this study aimed to elucidate whether an intervention on UPS with bortezomib, an inhibitor of UPS, may counteract the extensive myocardial infarction and increased inflammatory reaction into the hyperglycemic myocardium. METHODS: Ventricular biopsy specimens from 16 nondiabetic and 18 type 2 diabetic patients presenting with unstable angina who underwent coronary artery bypass were collected during coronary bypass surgery. Ejection fraction (EF); myocardial performance index (MPI), which measures both systolic and diastolic function, immunostaining, and cardiac levels of nitrotyrosine; UPS activity; NFkB; and TNF-alpha were investigated in both ischemic human myocardium and heart tissue from STZ-hyperglycemic rats subject to a myocardial ischemia/reperfusion procedure. RESULTS: We found that diabetic patients had higher MPI (P<.041) and reduced EF (P<.008) compared with nondiabetic patients. Diabetic specimens had higher nitrotyrosine, UPS activity, NFkB, and TNF-alpha levels compared with nondiabetic patients (P<.001). This was mirrored by consistently high levels of UPS and inflammatory markers in STZ-infarcted hearts, associated with high myocardial damage. In contrast, lesions from normoglycemic animals as well as from hyperglycemic rats treated with bortezomib showed low levels of ubiquitin-proteasome activity, inflammation, and myocardial damage (P<.01). CONCLUSIONS: By contributing to the increased inflammation, the UPS overactivity may enhance the risk of complication during myocardial ischemia in diabetic patients.