Astonishing response to Cetuximab in metastatic nasopharyn- geal carcinoma: a case report.

ABSTRACT: Nasopharyngeal carcinoma, one of the most common head and neck cancers in Southeast Asia, is uncommon in Western countries and it is frequently diagnosed in advanced stage. Chemotherapy given with radiation therapy, followed by more chemotherapy, is the standard of care of stage IV nasopharyngeal carcinoma but Cetuximab, an epidermal growth factor (EGFR) inhibitor, is now making its way in the treatment of locoregionally advanced nasopharyngeal carcinoma. We report a case of 58 years old patient with metastatic nasopharyngeal carcinoma with an astonishing response to Cetuximab. At the time of writing, the patient is still in treatment with Cetuximab with excellent disease control.

Daratumumab in multiple myeloma: experience of the multiple myeloma GIMEMA Lazio group.

Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.

Alkaline phosphatase (alp) levels in multiple myeloma and solid cancers with bone lesions: Is there any difference?

INTRODUCTION: Bone involvement in Multiple Myeloma results from increased osteoclast formation and activity that occurs in proximity to myeloma cells. The role of Alkaline Phosphatse (ALP) in this process and the diagnostic significance of plasma levels in patients with MM are unclear. AIM: To compare plasma ALP levels in patients with MM and solid cancers and metastatic lesions to the bone. RESULTS: In this observational retrospective study we enrolled 901 patients were enrolled: 440 patients (49%) with Multiple Myeloma, 461 (51%) with solid cancers. All 901 patients had bone lesions. Among patients with Multiple Myeloma, ALP values were mainly in the range of normality than those observed in patients with solid cancers and bone lesions. This difference is independent of stage, number and type of bone lesions. CONCLUSION: This study suggests that plasma ALP has a different clinical significance in MM than in other neoplasms and could be used as a discriminating marker in presence of bone lesions. In particular, lower or normal values, should suggest further investigations such as urinary and serum electrophoresis, associated with bone marrow aspirate in case of the presence of a monoclonal component, in order to confirm or exclude a MM diagnosis.

Survival After Lung Transplant for Cystic Fibrosis in Italy: A Single Center Experience With 20 Years of Follow-up.

OBJECTIVES: Lung transplantation is currently the only treatment for end-stage respiratory failure in patients with cystic fibrosis (CF). In this study we retrospectively analyzed our experience since the start of the transplantation program in 1996 with focus on survival analysis. METHODS: All patients with CF who underwent lung transplant at our center were included (1996-2016). Survival analysis after lung transplant was performed using the Kaplan-Meier estimate, comparing by sex and by 4 eras (1996-2000, 2001-2005, 2006-2010, and 2011-2016). RESULTS: In a 20-year period, 243 patients with CF were listed for lung transplant; 123 patients (61 male, 62 female) underwent transplant, and 85 died while waiting for donor organs. The mean (SD) and median age at transplant was 27.7 (8.7) years and 26.9 years (range, 9.1 - 52.1 years), respectively. Mean (SD) forced expiratory volume in the first second was 27.6 (9.7)% predicted; 115 patients (92.0%) were pancreatic insufficient, and 43 patients (34.0%) had CF-related diabetes. Removing patients with CF who died within the first 3 postoperative months, the mean (SD) and median survival after transplant were 8.2 (5.7) years and 7.5 years (range, 3 months-20 years), respectively. Overall post-lung transplant 1-year survival was 93.6%, 5-year survival was 71.4%, 10-year survival was 53.6%, 15-year survival was 36.7%, and 20-year survival was 31.6%. We found no difference in survival between sex (P = .22) and among the 4 eras (P = .56). CONCLUSIONS: Survival after lung transplant in our single center is similar to international data.

Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is only therapeutic option for patients affected by chronic respiratory failure. Chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is still the main cause of death and the most important factor that influences post-transplantation quality of life. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Extracorporeal photopheresis (ECP) seems to reduce the rate of lung function decline in transplant recipients with progressive BOS. METHODS: From 1991 until now, 239 LTs were performed at our center. Fifty-four patients (22.5%) developed BOS; 15 of these (27.7%) were treated with ECP. At the beginning of the treatment, all patients showed a mean decline of forced expiratory volume in 1 second (FEV1) from baseline values of 45.8% ± 17.2%; 2 patients were in long-term oxygen therapy. RESULTS: Mean follow-up from November 2013 to June 2016 was 11.6 ± 7 months. Twelve patients (80%) showed lung function stabilization with an FEV1 range after treatment between -6% to +8% from the pre-treatment values. We did not report any adverse effects or increase of infections incidence. DISCUSSION: ECP seems to be an effective and well-tolerated therapeutic option for LT patients with BOS in terms of stabilization of lung function and increased survival.

Do malignant diseases affect semen quality? Sperm parameters of men with cancers.

The advent of modern treatments together with the improvement of the surgical techniques has significantly increased 5-year survival rates of young patients with cancer. Although the deleterious effects of chemotherapy and radiation are well documented, controversies exist about the effect of cancer itself on semen parameters before treatment. We collected data on 236 patients representative of different types of cancers reoffered at our institution for sperm cryopreservation with the aim to correlate the pre-freeze semen parameters with type of cancer, disease stage and with semen quality of 102 fertile and healthy men. The median baseline semen parameters of all our patients with cancer are placed above the 5th percentile of the World Health Organization reference value, but the type of cancer may impact the sperm parameters. In testicular tumours and in Hodgkin lymphoma, we show a semen concentration statistically lower than in the fertile population, while in patients with other cancers, there is no difference with the healthy men. We found no correlation between semen quality and disease stage. Eighty-six per cent of our patients do not have children at the time of semen cryopreservation, and the only established clinical option for preserving fertility of these men is cryopreservation of spermatozoa.

Diagnostic and prognostic role of PET/CT in patients with chronic lymphocytic leukemia and progressive disease.

In order to evaluate the predictive value of positron emission tomography-computed tomography (PET/CT) in discriminating the presence of a Richter's syndrome (RS) or a second malignancy (SM), as well as to evaluate its prognostic value in patients with chronic lymphocytic leukemia (CLL), we retrospectively analyzed the data of 90 patients who, in the suspicion of a RS or a SM, underwent PET/CT followed by the biopsy of the involved tissue. The median maximum Standardized Uptake Value (SUV max) in the presence of a CLL/small lymphocytic lymphoma, a diffuse large B-cell lymphoma (DLBCL), a Hodgkin lymphoma (HL), a SM were 3.5, 14.6, 7.0 and 6.3, respectively (P ⩽ 0.0001). A SUV max cutoff value ⩾ 5 showed a sensitivity, specificity, positive and negative predictive values of 88.2, 71.2, 51.3 and 94%, respectively, for the presence of a more aggressive disease (DLBCL, HL and SM). A SUV max ⩾ 5 identified also a subset of treatment naive patients with an inferior progression-free survival (P = 0.011) and overall survival (P = 0.067). These findings suggest that PET/CT may helpfully integrate the biologically-based prognostic stratification of CLL. Prospective clinical trials including larger cohorts of patients are needed to conclusively define the role and prognostic impact of PET/CT in the routine management of CLL patients.

Burkholderia pyrrocinia in cystic fibrosis lung transplantation: a case report.

Infection with Burkholderia species is typically considered a contraindication leading to transplantation in cystic fibrosis (CF). However, the risks posed by different Burkholderia species on transplantation outcomes are poorly defined. We present the case of a patient with CF who underwent lung transplantation due to a severe respiratory failure from chronic airways infection with Burkholderia pyrrocinia (B. cepacia genomovar IX) and pan-resistant Pseudomonas aeruginosa. The postoperative course was complicated by recurrent B. pyrrocinia infections, ultimately lea ding to uncontrollable sepsis and death. This is the first case report in CF of Burkholderia pyrrocinia infection and lung transplantation, providing further evidence of the high risk nature of the Burkholderia species.

Folate, vitamin B12 and homocysteine status in an Italian blood donor population.

BACKGROUND AND AIMS: The relevance of folate, other B-vitamins and homocysteine (Hcy) for the occurrence or prevention of several diseases has induced growing interest. Unfortunately, little evidence is available regarding B-vitamin concentrations in Italy. This study evaluated in a region of middle-southern Italy, folate, vitamin B12 and Hcy concentrations and the prevalence of their ideal blood levels. The main determinants of B-vitamins and Hcy were also considered. METHODS AND RESULTS: Male and female blood donors (n=240), aged 18-66 years and living in Molise region (Italy), were enrolled in the study. They completed a brief questionnaire concerning fruit and vegetables intake, physical activity and smoking; serum and red blood cell (RBC) folate and serum vitamin B12 were measured by an immunoassay on an automated analyzer. Total Hcy was measured by high performance liquid chromatography (HPLC). Geometric means of serum folate, RBC folate and serum vitamin B12 were 10.8nmoll(-1), 426.0nmoll(-1) and 245.0pmoll(-1), respectively. Only 22.5%, 24.2% and 16.3% of blood donors showed an adequate level of serum folate, RBC folate or serum vitamin B12 respectively. When a cut-off of RBC folate ≥906nmoll(-1) was used no women of childbearing age had adequate levels. A geometric mean of 14.0µmoll(-1) was found for total Hcy, with an ideal concentration in 12.1% of subjects. Folate concentration was higher in women and non-smokers and in subjects with higher consumption of fruit and vegetable. CONCLUSION: This study shows a low-moderate B-vitamins status in middle-southern Italy, associated with an inadequate fruit and vegetable consumption. A public health strategy should be undertaken to encourage a B-vitamin-rich diet with the addition of vitamin supplements or vitamin fortified foods in population subgroups with special needs.

[The age factor in bilateral hydrocele diagnosis secondary to a primitive testis lymphoma: case report, diagnosis and therapy]. / Il fattore età nella diagnosi clinica di idrocele bilaterale da linfoma primitivo del testicolo: caso clinico e considerazioni diagnostico-terapeutiche.

Primitive NHL represents 9% of testis tumours and the 85% is diagnosed in patient older thant 60 years old. Usually pain and a testis mass are the main manifestations. The Authors report the case of a 82 years-old man with bilateral hydrocele causing severe alteration in the deambulation. The cytology did not show blood cells or neoplastic cell in the FNAB. The US showed a complete modification in the testis. The patient underwent to surgery intervention of vaginalis tunic eversion and resection with the aim of control the symptoms. The histology on multiple biopsy of testis and epidydims bilaterally showed a large B-cell lymphoma. The patient was treated with 6 chemotheray cycles (Rituximab, Vincristine, Cyclophosphamide, Prednisone). Bilateral hydrocele is a rare clinical presentation of testis NHL. In this patient, blood and neoplastic cell absence in the cytology made difficult the differential diagnosis between inflammatory pathology and neoplasia. Hystopathologic study and immunologic pattern can make a certain diagnosis.

A new xenicane norditerpene from the Indian marine gorgonian Acanthogorgia turgida.

Chemical investigation of the liposoluble extract of the gorgonian Acanthogorgia turgida, from Indian coasts, led us to isolate a new xenicane-based norditerpene, isoacalycixeniolide-A (1), along with the known structurally related compounds 2-6. The structure of the norditerpene (1) was elucidated by spectral methods (mainly by NMR techniques), whereas the absolute stereochemistry was suggested by the application of circular dicroism methodology.

Lung transplantation for cystic fibrosis in Italy.

Lung transplantation (LT) is the only effective form of therapy for cystic fibrosis (CF) associated with end-stage pulmonary failure. In Italy, the management of CF is regulated by national law, which has instituted regional centers for care and follow-up of all CF patients. LT has been performed since 1992 in only nine LT certified centers. The structured national organization has led to a unified database for LT for CF. As of December 2006, 197 bilateral LT (96 male and 94 female patients; 7 retransplants) have been performed. Of these, four had also liver or heart and liver transplantation, and three are long-term survivors. Overall median survival is 7 years. Mean age at transplantation is 26.5 years, and the mortality on the waiting list is 33.6%. Patients listed for transplant either received a suitable donor within a mean of 10 months or died within a mean of 5.5 months. The most frequent cause of death is bronchiolitis obliterans syndrome (BOS). Our nationwide database indicates the excellent results obtained by LT in FC. Still, mortality on the waiting list remains a challenge and long-term outcome is limited by BOS.

Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/progenitor cells: therapeutic potential of cell reprogramming.

During embryonic development and adult life, the plasticity and reversibility of modifications that affect the chromatin structure is important in the expression of genes involved in cell fate decisions and the maintenance of cell-differentiated state. Epigenetic changes in DNA and chromatin, which must occur to allow the accessibility of transcriptional factors at specific DNA-binding sites, are regarded as emerging major players for embryonic and hematopoietic stem cell (HSC) development and lineage differentiation. Epigenetic deregulation of gene expression, whether it be in conjunction with chromosomal alterations and gene mutations or not, is a newly recognized mechanism that leads to several diseases, including leukemia. The reversibility of epigenetic modifications makes DNA and chromatin changes attractive targets for therapeutic intervention. Here we review some of the epigenetic mechanisms that regulate gene expression in pluripotent embryonic and multipotent HSCs but may be deregulated in leukemia, and the clinical approaches designed to target the chromatin structure in leukemic cells.

Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features.

Although the occurrence of thrombosis in acute promyelocytic leukemia (APL) has been reported during retinoic acid treatment, no studies carried out in large clinical cohorts have specifically addressed this issue. We analyzed 124 APL patients treated with the all-trans retinoic acid and idarubicin protocol and compared clinico-biologic characteristics of 11 patients who developed thrombosis with those of 113 patients who had no thrombosis. In seven patients, the events were recorded during induction, whereas in four patients deep vein thrombosis occurred in the post-induction phase. Comparison of clinico-biological characteristics of patients with and without thrombosis revealed in the former group higher median white blood cell (WBC) count (17 x 10(9)/l, range 1.2-56, P=0.002), prevalence of the bcr3 transcript type (72 vs 48%, P=0.01), of FLT3-ITD (64 vs 28%, P=0.02), CD2 (P=0.0001) and CD15 (P=0.01) expression. No correlation was found with sex, age, French-American-British subtype, all-trans-retinoic acid syndrome or with thrombophilic state that was investigated in 5/11 patients. Our findings suggest that, in APL patients consistent biologic features of leukemia cells may predict increased risk of developing thrombosis.

3-Oxo-axisonitrile-3, a new sesquiterpene isocyanide from the Chinese marine sponge Acanthella sp.

A new sesquiterpene isocyanide, 3-oxo-axisonitrile-3 (1), with a spiro [5,6] decane skeleton (spiroaxane) together with a known related sesquiterpene isonitrile (2), sesquiterpene isothiocyanates (3-8) and two diterpene isonitriles (9, 10) have been isolated from the Chinese marine sponge Acanthella sp. The structure of 1 has been determined on the basis of spectroscopic analysis.

A new spiro-sesquiterpene from the sponge Dysidea fragilis.

A new spiro-sesquiterpene, spirofragilin (1), along with a known related sesquiterpene, dehydroherbadysidolide (2), have been isolated from the marine sponge Dysidea fragilis collected in the South China Sea. The structure of 1 was elucidated on the basis of detailed spectroscopic analysis.

Characterization of carbons from olive cake by sorption of wastewater pollutants.

Studies has been conducted to compare the sorption properties between raw carbons made from olive cake and commercial activated carbons to remove aquatic pollutant such as heavy metal (HM), phenol (Ph), dodecylbenzenesulfonic acid-sodium salt detergent (DBSNa) and methylene blue dye (MB). Effect of acidic treatments by H2SO4, HCl and HNO3 on the sorption properties of olive cake carbon (OCC) were studied by mass titration, SEM photographs, sorption isotherms. It is found that acidic treatment changes the surface properties of OCC but do not enhance its sorption capacity. Compared to commercial activated carbons the OCC derivatives generally are equally able to uptake HM and Ph from solution but MB and DBSNa are not. This different behaviour is to attribute to manufacturing and activation treatments so as surface groups of the precursor sorbent material. For the heavy metals, chromium and silver were removed effectively but to small extent cadmium. This may be because of the various charge densities of metal elements tested. The results of the multiple experiments indicate that sorption of cadmium ions can be significantly improved by the presence of complexing agents sorbed from the carbon. An empirical mathematical form is proposed to correlate experimental data and to compare the performance of the different sorbent materials.