Giuseppina P. Dognini

The addition of rituximab to anthracycline‐based chemotherapy significantly improves outcome in ‘Western’ patients with intravascular large B‐cell lymphoma

Some case reports and a Japanese series suggest benefit from the use of rituximab in patients with intravascular large B‐cell lymphoma (IVL). Rituximab efficacy was evaluated in Western patients with IVL, comparing outcome of 10 patients treated with rituximab + chemotherapy (R‐CT) and of 20 patients treated with chemotherapy alone (CT). There were no significant differences in patients’ characteristics between the two subgroups. The addition of rituximab was associated with improved complete remission rate (90% vs. 50%; P = 0·04), event‐free survival (3‐year: 89% vs. 35%; P = 0·003) and overall survival (3‐year: 89% vs. 38%; P = 0·01). In conclusion, rituximab may substantially change the dismal prognosis of IVL.

Six-month oral clarithromycin regimen is safe and active in extranodal marginal zone B-cell lymphomas: final results of a single-centre phase II trial.

Antibiotics could be included in the long list of anticancer candidates by virtue of their good tolerability and direct proapoptotic effect on tumour cells. This effect is achieved by means of multiple antiproliferative mechanisms that deserve to be better explored. Among others, macrolides have been proposed as potential antineoplastic and immunomodulatory agents. They enhance the antitumour activity of macrophages, natural killerand CD8 cytotoxic T-cells, reduce neutrophil production of interleukin-8, and inhibit tumour necrosis factor-a and vascular endothelial growth factor activity (Aoki et al, 2005). Clarithromycin is a substrate of P-glycoprotein, induces apoptotic changes in tumour cells and exhibits antitumour activity in different murine cancer models (Wakasugi et al, 1998; Hamada et al, 2000). These preclinical data constitute the rationale for prospective clinical trials addressing the antineoplastic activity of macrolides. In particular, the combination of clarithromycin with other immunomodulatory agents has been associated with encouraging results in prospective trials on multiple myeloma and Waldenström macroglobulinemia (Niesvizky et al, 2008). Additionally, anecdotal case reports suggest an antineoplastic effect of clarithromycin in patients with marginal zone B-cell lymphoma (MZL) of the gastrointestinal tract (Arima & Tsudo, 2003; Matsumoto & Iida, 2005). Given its indolent behaviour, extranodal MZL (EMZL) is a suitable candidate to test the potential direct anticancer effect of macrolides. On this basis, we designed a pilot phase II trial to address the feasibility and activity of a 6-month oral clarithromycin regimen as exclusive treatment in patients with relapsed/refractory EMZL. The trial conformed to the tenets of the Declaration of Helsinki, and was approved by the Institutional Review Board of the San Raffaele Scientific Institute. From June 2006 to May 2008, 13 patients (median age 57 years, range 36–80 years; seven males) with relapsed/ refractory EMZL, Eastern Cooperative Oncology Group (ECOG) performance status (PS) £3 and at least one measurable or parametrable lesion were registered. Baseline assessment included physical examination, haemogram and biochemical profile, human immunodeficiency virus, hepatitis C virus (HCV) and hepatitis B virus serology, total body computed tomography scan, gastroscopy, and bone marrow biopsy. All patients were tested for Helicobacter pylori (Hp)

Chlamydophila psittaci is viable and infectious in the conjunctiva and peripheral blood of patients with ocular adnexal lymphoma: Results of a single‐center prospective case–control study

Ocular adnexal MALT lymphoma (OAML) is linked to Chlamydophila psittaci (Cp) infection. Viability and infectivity of Cp, demonstrated by growth in culture, has not been yet investigated in these patients. We conducted a single‐center prospective case–control study to assess the prevalence, viability and infectivity of Cp in 20 OAML patients and 42 blood donors registered in a 6‐month period. The presence of Cp in conjunctival swabs and peripheral blood mononuclear cells (PBMC) of patients and donors was assessed by TETR‐PCR and in vitro cultures. From an epidemiological point of view, OAML patients often resided in rural areas, and reported a history of chronic conjunctivitis and prolonged contact with household animals (85% vs. 38% of donors; p = 0.00001). Cp was detected in lymphoma tissue in 15 (75%) patients. Cp DNA was detected in conjunctival swabs and/or PBMC from 10 (50%) patients and in PBMC from 1 (2%) donor (p = 0.01). Viability and infectivity of Cp, demonstrated by growth in culture, were confirmed in conjunctival swabs and/or PBMC from 5 (25%) patients, but not in donors (p = 0.002). This prospective study demonstrates, for the first time, that Cp present in the conjunctiva and PBMC of OAML patients is capable to grow and be isolated in cell cultures. Cp infection is common in OAML patients and exceptional in blood donors. Epidemiological data of OAML patients (prolonged contact with household animals and chronic conjunctivitis) are consistent with Cp exposure risk.

Telmisartan: just an antihypertensive agent? A literature review

Introduction: The modulation of the renin angiotensin aldosterone system (RAAS) is an important pathway in managing high blood pressure, and its overexpression plays a key role in target end-organ damage. Telmisartan is an angiotensin II receptor blocker (ARB) with unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a significant and 24-h sustained reduction of blood pressure. Telmisartan has well-known antihypertensive properties, but there is also strong clinical evidence that it reduces left ventricular hypertrophy, arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. Areas covered: This paper reviews telmisartans pharmacological properties in terms of efficacy for hypertension control and, importantly, focuses on its new therapeutic indications and their clinical implications. Expert opinion: ONTARGET (ongoing telmisartan alone and in combination with ramipril global endpoint trial) demonstrated, that telmisartan confers cardiovascular protective effects similar to those of ramipril, but with a better tolerability. Moreover, recent investigations focused on the capability of telmisartan to modulate the peroxisome proliferator-activated receptor-gamma (PPAR-γ), an established target in the treatment of insulin resistance, diabetes and metabolic syndrome, whose activation is also correlated to anti-inflammatory and, finally, anti-atherosclerotic properties. Telmisartan shows peculiar features that go beyond blood pressure control. It presents promising and unique protective properties against target end-organ damage, potentially able to open a scenario of new therapeutic approaches to cardiovascular disease.

Exposure to animals and increased risk of marginal zone B-cell lymphomas of the ocular adnexae

Background:Ocular adnexal marginal zone B-cell lymphoma (OAMZL) has been associated with Chlamydophila psittaci, an infection that may be transmitted by carrier animals. However, it is still unclear whether exposure to animals affects the risk of OAMZL in comparison with other lymphoma histotypes. We therefore investigated the role of professional and/or domestic exposures to animals in the occurrence of OAMZL, as compared with other types of lymphoma.Methods:A hospital-based case–control study was carried out on 43 consecutive OAMZL patients (cases) and 87 consecutive patients with nodal non-Hodgkins lymphomas (NHLs; controls). Multiple logistic regression (MLR) odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the association between exposures to animals and OAMZL risk.Results:A higher proportion of cases reported a lifetime exposure to household animals (79.1% vs 64.4% among controls), with a non-statistical significant MLR-OR of 2.18 (95% CI: 0.85–5.62). The OAMZL cases more frequently reported a history of occupation in breeding and/or slaughtering than controls (34.9% vs 6.9%), with an overall increased risk of 7.69 (95%CI: 2.65–22.34).Conclusion:These results indicate that, compared with nodal NHLs, the risk of OAMZL is markedly increased by contact with animals, particularly by occupational exposures.

Therapeutic management of ocular adnexal MALT lymphoma.

Non-Hodgkin lymphomas constitute 50% of all orbital malignancies. Mucosa-associated lymphoid tissue (MALT)-type lymphoma is the most common histology category in this anatomic region. Ocular adnexal lymphoma of MALT-type is an indolent and rarely lethal malignancy that can often be managed with observation alone. Occasionally, lymphomatous lesions determine the symptoms that condition a patient’s quality of life, and so require an immediate antineoplastic treatment. Several strategies are available, but reliable indications supported by prospective trials do not exist. Some therapeutic strategies are associated with substantial side effects and require a well-balanced therapeutic decision, which should take into account several variables related to the patient, the lymphoma, and the treatment itself. In this review, the authors analyze related literature and propose therapeutic guidelines for the management of ocular adnexal lymphoma of MALT-type.

Hypertension and survival in renal cell carcinoma treated with anti-VEGFR agents: a systematic review and meta-analysis

Antiangiogenetics (AAG) are drugs that are commonly used to treat a number of neoplasms, including renal cell carcinoma (RCC). They exert their activity by inhibiting the vascular endothelial growth factor pathway. Hypertension (HTN) represents one of the most common side effects secondary to AAG employment, and recent studies seem to suggest rising evidence of a possible relationship between AAG-related hypertension (AAG-HTN) and a better outcome for patients. The aim of this meta-analysis was to verify the hypothesis that AAG-HTN might represent a prognostic factor in advanced RCC. A total of 15 out of 434 studies were included, which explored the prognostic impact of HTN, and reported a hazard ratio and 95% confidence interval for overall survival (OS) and progression-free survival (PFS). AAG-HTN development was positively related to both OS and PFS, and all possible clinical implications and the potential role of AAG-HTN as a prognostic marker are discussed.

5C.06: HYPERTENSION AND CARDIOVASCULAR RISK FACTORS: A SHOT ON NORTHERN ITALY POPULATION IN REAL LIFE SETTING.

Objective: Hypertension (HT) represents the most important cardiovascular (CV) risk factor and blood pressure (BP) measurements are generally performed in medical settings, while data deriving from real life are generally poor. This work was conducted during public events out of medical setting (i.e. world hypertension day) in order to assess the prevalence of HT and evaluate other CV risk factors. Design and method: Each participating subject, after signing an informed consent, was asked to fulfil a questionnaire investigating his/her comorbidities, CV risk factors and ongoing therapies. BP measurement was performed according to the ESH/ESC guidelines. A brief counselling was then offered and brochures dealing with HT prevention provided. Results: Between May 2011 and May 2014, 1540 subjects were evaluated (mean age = 58y, median = 60y, range = 12–102y, M = 696, F = 845, M/F = 0.82). Among them, 890 (58%) declared themselves «normotensive» (mean age = 52y, median = 53y, range = 12–86, M = 408, F = 482) and 650 (42%) «hypertensive» (mean age = 65y, median = 66, range: = 22–102, M = 287, F = 363). BP measurement resulted < 140/90mmHg in 1137 subjects(=74%). Among them, 408 belonged to the «hypertensive» group, thus representing pts reaching the target pressure (=63%). On the contrary, BP > 140/90mmHg was observed in 403 subjects(=26%), 242 of them belonging to the «hypertensive» group (=non target pts) and 161 to those previously declaring «normotensive». CV risk factors were analysed, the most represented being dyslipidaemia (N = 441), smoke(N = 216), Type 2 Diabetes(N = 121), Coronary artery disease(N = 110), cerebrovascular disease(N = 44). All these risk factors were significantly more expressed in «hypertensive» pts. Number of CV risk factors was 0, 1, 2, 3, > 4 respectively for 500, 522, 312, 150, and 55 subjects. Thirty-five % of «hypertensive» pts had no other CV risk factor, but a significantly higher number of CV risk factors emerged respect to «normotensives». Conclusions: Despite the possible bias, our data provide a picture of the status of pts out of medical setting. Epidemiological data and CV risk factors were analysed, suggesting, as expected, a higher number of CV risk factors in “hypertensive” pts.

Antiangiogenetic-induced hypertension and improved outcome in cancer patients.

e21651Background: Hypertension (HTN) is one of the most common adverse events observed during treatment with antiangiogenetic drugs (AAG) inhibiting the Vascular Endothelial Growth Factor Pathway. ...