Lenalidomide plus R-CHOP21 in newly diagnosed diffuse large B-cell lymphoma (DLBCL): long-term follow-up results from a combined analysis from two phase 2 trials.

Lenalidomide-RCHOP (R2-CHOP21) has been shown to be safe and effective in patients with untreated diffuse large B-cell lymphoma (DLBCL). The aim of this analysis is to report long-term outcome and toxicities in newly diagnosed DLBCL patients who received R2-CHOP21 in two independent phase 2 trials, conducted by Mayo Clinic (MC) and Fondazione Italiana Linfomi (FIL). All patients received R-CHOP21 plus lenalidomide. Long-term progression-free survival (PFS), time to progression (TTP), overall survival (OS) and late toxicities and second tumors were analyzed. Hundred and twelve patients (63 MC, 49 FIL) were included. Median age was 69 years, 88% were stage III-IV. At a median follow-up of 5.1 years, 5y-PFS was 63.5%, 5y-TTP 70.1% and 5y-OS 75.4%; according to cell of origin (COO): 5y-PFS 52.8% vs 64.5%, 5y-TTP 61.6% vs 69.6% and 5y-OS 68.6% vs 74.1% in germinal center (GCB) vs non-GCB respectively. Four patients experienced grade 4-5 late toxicities. Grade ≤ 3 toxicities were infections (N = 4), thrombosis (N = 1) and neuropathy (N = 3). Seven seconds tumors were observed. Long-term follow-up demonstrates that R2-CHOP21 efficacy was maintained with high rates of PFS, TTP, and OS. Lenalidomide appears to mitigate the negative prognosis of non-GCB phenotype. Incidence of therapy-related secondary malignancies and late toxicities were low.

Early application of percutaneous vertebroplasty reduces pain without affecting peripheral blood stem cell (PBSC) collection and transplant in newly diagnosed multiple myeloma (MM) patients.

Vertebral fractures occur in over 60% of newly diagnosed multiple myeloma (MM) patients and can cause pain, disability and poor quality of life. Antimyeloma therapy can lead to symptoms improvement, but these effects can take time to be perceived. Application of radiotherapy prior to peripheral blood stem cells (PBSC) mobilisation can impair stem cell collection. Percutaneous vertebroplasty has been proposed as a suitable option to rapidly relieve bone pain from vertebral fractures in MM patients, but, little is known about the effects of this procedure on subsequent PBSC mobilisation, collection and transplant. Eighteen patients (10M/8F, median age 64.5 years) with untreated MM and painful vertebral lesions underwent vertebroplasty prior to proceed to the planned transplant program at our Institution. Forty-one procedures were performed at C2-L5 levels, eight patients were treated at ≥2 levels. Ninety-five per cent of the cases obtained a complete or optimal pain control. All the patients successfully mobilised PBSC (median CD34+ cells = 10.8 × 10(6) /kg) and underwent autologous PBSC transplant; both polymorphonucleates and platelets recovery averaged 11 days. Our data seem to suggest that percutaneous vertebroplasty is useful in newly diagnosed MM patients with painful vertebral fractures as it allows rapid and durable achievement of pain control, without interfering with further treatment.

Genista sessilifolia DC. extracts induce apoptosis across a range of cancer cell lines.

OBJECTIVES: Restorative properties of medicinal plants such as Genista sessilifolia DC. have often been suggested to occur, in epidemiological studies. However, full characterization of effective principles responsible for this action has never previously been performed. Here, we have characterized G. sessilifolia's anti-cancer effects and identified the chemical components involved in this anti-tumour action. MATERIALS AND METHODS: Cell cycle, apoptosis, necrosis, differentiation analyses, high-performance liquid chromatography, western blotting, RNA extraction, real-time PCR and primers have all been observed/used in the study. RESULTS: We report that G. sessilifolia methanol extract has anti-cancer activity on solid and haematological cancer cells. G. sessilifolia extract's anti-proliferative action is closely bound to induction of apoptosis, whereas differentiation is only weakly modulated. Analysis of G. sessilifolia extract, by high-performance liquid chromatography, identifies fraction 18-22 as the pertinent component for induction of apoptosis, whereas fractions 11-13 and 27-30 both seem to contribute to differentiation. G. sessilifolia extract induces apoptosis mediated by caspase activation and p21, Rb, p53, Bcl2-associated agonist of cell death (BAD), tumour necrosis factor receptor super-family, member 10 (TRAIL) overexpression and death receptor 5 (DR5). Accordingly, fraction 18-22 inducing apoptosis was able to induce TRAIL. CONCLUSIONS: Our results indicate that G. sessilifolia extract and its fraction 18-22 containing genistin and isoprunetin, were able to induce anti-cancer effects supporting the hypothesis of a pro-apoptotic intrinsic content of this natural medicinal plant.

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model.

OBJECTIVES: Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model. MATERIALS AND METHODS: Groups of cancerized hamsters were locally exposed to single or double (2 or 4 weeks apart) applications of BNCT at different dose levels, mediated by the boron compounds boronophenylalanine (BPA) or BPA and decahydrodecaborate (GB-10) administered jointly. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumour development from field-cancerized tissue and mucositis were followed for 8 months. RESULTS: A double application (4 weeks apart) of BNCT mediated by GB-10+ BPA at a total dose of 10 Gy in two 5-Gy doses rendered the best therapeutic advantage (63-100% inhibition of tumour development from field-cancerized tissue), minimizing dose-limiting mucositis. CONCLUSION: BNCT can be optimized for the integral treatment for head and neck cancer, considering the implications for field-cancerized tissue.

Update on the role of autologous hematopoietic stem cell transplantation in multiple myeloma.

Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achiving a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

Circulating cytokines present in the serum of peripheral arterial disease patients induce endothelial dysfunction.

Peripheral arterial disease (PAD) is a chronic condition caused by atherosclerosis and is a severe complication of type 2 diabetes (T2D). We hypothesised that chronic condition of arterial disease engenders inflammation and endothelial damage in response to circulating cytokines released in the blood stream of PAD patients. We explored the levels of circulating cytokines in PAD patients with and without diabetes by multiplex cytokine array compared with non-PAD controls. Serum from PAD patients with or without diabetes showed high levels of VEGF, IFN-gamma, TNF-alpha, MCP-1, and EGF. VEGF levels correlated with TNF-alpha and IFN-gamma, significantly. Endothelial cells (ECs) were exposed to the different altered cytokines to evaluate changes in cell growth, migration and tubule-like formation, displaying impairment on proliferation, migration and tubule formation. Our findings demonstrate that a set of cytokines is significantly increased in the serum of PAD patients. These cytokines act to induce endothelial dysfunction synergistically. VEGF strongly correlated with TNF-alpha and IFN-gamma, opening new therapeutic perspectives.

Mitochondrial electron transport and glycolysis are coupled in articular cartilage.

OBJECTIVE: Although the majority of the adenosine triphosphate (ATP) in chondrocytes is made by glycolysis rather than by oxidative phosphorylation in mitochondria there is evidence to suggest that reactive oxygen species produced by mitochondrial electron transport (ET) help to maintain cellular redox balance in favor of glycolysis. The objective of this study was to test this hypothesis by determining if rotenone, which inhibits ET and blocks oxidant production inhibits glycolytic ATP synthesis. DESIGN: Bovine osteochondral explants were treated with rotenone, an ET inhibitor; or oligomycin an ATP synthase inhibitor; or 2-fluoro-2-deoxy-D-glucose, a glycolysis inhibiter; or peroxide, an exogenous oxidant; or mitoquinone (MitoQ), a mitochondria-targeted anti-oxidant. Cartilage extracts were assayed for ATP, nicotine adenine dinucleotide (NAD+/H), and culture medium was assayed for pyruvate and lactate after 24 h of treatment. Imaging studies were used to measure superoxide production in cartilage. RESULTS: Rotenone and 2-FG caused a significant decline in cartilage ATP (P < 0.001). In contrast, ATP levels were not affected by oligomycin. Peroxide treatment blocked rotenone effects on ATP, while treatment with MitoQ significantly suppressed ATP levels. Rotenone and 2-FG caused a significant decline in pyruvate, but not in lactate production. NADH:NAD+ ratios decreased significantly in both rotenone and 2-FG-treated explants (P < 0.05). Rotenone also significantly reduced superoxide production. CONCLUSIONS: These findings showing a link between glycolysis and ET are consistent with previous reports on the critical need for oxidants to support normal chondrocyte metabolism. They suggest a novel role for mitochondria in cartilage homeostasis that is independent of oxidative phosphorylation.

Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.

OBJECTIVES: Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. MATERIALS AND METHODS: We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. RESULTS: We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. CONCLUSIONS: Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation.

Shifting from open surgical cut down to ultrasound-guided percutaneous central venous catheterization in children: learning curve and related complications.

PURPOSE: Tunneled indwelling central venous catheters (CVC) are essential in the management of children with cancer, hematological, nephrological disorders and for parenteral nutrition. The aim of this study is to present the experience of a single center of the transition from traditional open surgical cut down procedure (OSC) to ultrasound (US)-guided percutaneous CVC insertion, focusing on learning curve and related complications. METHODS: All CVCs inserted between April 2008 and November 2009 in children at the Gaslini Children Hospital were revised, and data on methods of cannulation, intraoperative and device-related complications and re-intervention were recorded. RESULTS: 194 CVCs were positioned in 188 patients. 128 out of 194 CVCs were positioned through an OSC technique, whereas the remaining 66 CVCs were inserted percutaneously with US guidance. Of the 27 recorded complications, 15 were mechanical events, 7 cases developed infection, whereas the remaining 5 (2.6%) were classified as intraoperative complications. A second surgical procedure was described in 23 (11.8%) cases. CONCLUSION: Shifting from OSC to US-guided percutaneous CVC insertion inevitably involves a challenging learning curve which is generally associated with high complication rates. Complications progressively decrease once a good experience in US guidance and percutaneous technique has been obtained.

Management of bleeding and of invasive procedures in patients with platelet disorders and/or thrombocytopenia: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET).

The optimal management of bleeding or its prophylaxis in patients with disorders of platelet count or function is controversial. The bleeding diathesis of these patients is usually mild to moderate: therefore, transfusion of platelet concentrates may be inappropriate, as potential adverse effects might outweigh its benefit. The availability of several anti-hemorrhagic drugs further compounds this problem, mainly because the efficacy/suitability of the various treatment options in different clinical manifestations is not well defined. In these guidelines, promoted by the Italian Society for Studies on Haemostasis and Thrombosis (Società Italiana per lo Studio dell'Emostasi e della Trombosi [SISET]), we aim at offering the best available evidence to help the physicians involved in the management of patients with disorders of platelet count or function. Literature review and appraisal of available evidence are discussed for different clinical settings and for different available treatments, including platelet concentrates (PC), recombinant activated factor VII, desmopressin, antifibrinolytics, aprotinin and local hemostatic agents.

Incidence of indwelling central venous catheter-related complications using the Sri Paran technique for device fixation in children with cancer.

PURPOSE: Mechanical complications in tunneled indwelling central venous catheters (CVCs) often involve a risk of displacement. Fixation procedures are, therefore, of primary importance. We prospectively evaluated the incidence of CVC-related mechanical and infectious complications observed in devices fixated with the Sri Paran technique. METHODS: All CVCs inserted in children with cancer at our Institution from October 2005 to January 2007 were prospectively monitored for device-related mechanical and infectious complications. The Sri Paran fixation technique was used in all cases. The complication rate per 1,000 days was calculated as 1,000 times the number of complications divided by the total number of catheter days. RESULTS: Ninety-five CVCs were positioned in 84 children. The overall length of observation ranged between 41 and 482 days for a total of 18,618 catheter days. Mechanical complications occurred in 5% of the devices (specific rate 0.27); infections were observed in 6% of the devices (specific rate 0.32). No complications were observed during the first 30 days after CVC insertion. CONCLUSIONS: The results, we obtained with the Sri Paran technique are extremely encouraging. Yet, randomized studies are required to prove these preliminary data.

Dosimetry and radiobiology at the new RA-3 reactor boron neutron capture therapy (BNCT) facility: application to the treatment of experimental oral cancer.

The National Atomic Energy Commission of Argentina (CNEA) constructed a novel thermal neutron source for use in boron neutron capture therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The aim of the present study was to perform a dosimetric characterization of the facility and undertake radiobiological studies of BNCT in an experimental model of oral cancer in the hamster cheek pouch. The free-field thermal flux was 7.1 x 10(9) n cm(-2)s(-1) and the fast neutron flux was 2.5 x 10(6) n cm(-2)s(-1), indicating a very well-thermalized neutron field with negligible fast neutron dose. For radiobiological studies it was necessary to shield the body of the hamster from the neutron flux while exposing the everted cheek pouch bearing the tumors. To that end we developed a lithium (enriched to 95% in (6)Li) carbonate enclosure. Groups of tumor-bearing hamsters were submitted to BPA-BNCT, GB-10-BNCT, (GB-10+BPA)-BNCT or beam only treatments. Normal (non-cancerized) hamsters were treated similarly to evaluate normal tissue radiotoxicity. The total physical dose delivered to tumor with the BNCT treatments ranged from 6 to 8.5 Gy. Tumor control at 30 days ranged from 73% to 85%, with no normal tissue radiotoxicity. Significant but reversible mucositis in precancerous tissue surrounding tumors was associated to BPA-BNCT. The therapeutic success of different BNCT protocols in treating experimental oral cancer at this novel facility was unequivocally demonstrated.

Forum on: the role of recombinant factor VIII in children with severe haemophilia A.

The development of recombinant FVIII (rFVIII) products, fuelled by the need for improved safety of treatment arising from the dramatic widespread blood-borne virus transmission in the 1970-1980s revolutionized the care of children with haemophilia A over the last two decades. The larger availability of perceived safer replacement therapy associated with the introduction of rFVIII products reassured the haemophilia community and there was a strong push in some Western countries to treat haemophilic children only with rFVIII. Moreover, this significantly contributed in the 1990s to the diffusion outside Northern Europe of prophylactic regimens implemented at an early age to prevent bleeding and the resultant joint damage (i.e. primary prophylaxis), together with the possibility of home treatment. These changes led to a substantial improvement of the quality of life of haemophilic children and of their families. The general agreement that primary prophylaxis represents the first-choice treatment for haemophilic children has been recently supported by two randomized controlled trials carried out with rFVIII products, providing evidence on the efficacy of early prophylaxis over on-demand treatment in preserving joint health in haemophilic children. However, the intensity and optimal modalities of implementation of prophylaxis in children, in particular with respect to the issue of the venous access, are still debated. A number of studies also supports the role of secondary prophylaxis in children, frequently used in countries in which primary prophylaxis was introduced more recently. With viral safety now less than an issue and with the more widespread use of prophylaxis able to prevent arthropathy, the most challenging complication of replacement therapy for children with haemophilia remains the risk of inhibitor development. Despite conflicting data, there is no evidence that the type of FVIII concentrate significantly influences the complex multifactorial process leading to anti-FVIII alloantibodies, whereas other treatment-related factors are likely to increase (early intensive treatments due to surgery or severe bleeds) or reduce (prophylaxis) the risk. Although the optimal regimen is still uncertain, eradication of anti-FVIII antibodies by immune tolerance induction (ITI), usually with the same product administered at inhibitor detection, should be the first-choice treatment for all patients with recent onset inhibitors. This issue applies particularly to children, as most patients undergo ITI at an early age, when inhibitors usually appear. The availability of a stable and long-lasting venous access represents a leading problem also in this setting. These and other topics concerning rFVIII treatment of haemophilic children were discussed in a meeting held in Rome on 27 February 2008 and are summarized in this report.

Intratumoral vs systemic administration of meta-tetrahydroxyphenylchlorin for photodynamic therapy of malignant gliomas: assessment of uptake and spatial distribution in C6 rat glioma model.

Malignant gliomas, with an incidence of 5 cases per 100,000 population per year, represent the most common primary brain tumour. They have an overall survival length of less than 2 years. Many different adjuvant therapies have been developed. Among them, Photodynamic Therapy (PDT), that is based on photochemical reactions between light and tumoral tissue selectively labelled with exogenous photosensitizing agents. Among photosensitizers, m-THPC (Temoporfin), seems to be the most promising one for the treatment of brain tumors, but, unfortunately, it causes problems of high skin photosensitivity. To by-pass this problem, we devised an intratumoral route of administration of this photosensitizer. The aim of this study is to investigate and compare the uptake of m-THPC in brain tumor and normal tissue after systemic and intratumoral administration of the drug. 30 female Wistar rats received m-THPC 12 days after C6 tumor implantation. Temoporfin was administered intratumorally in 24 rats at two different concentrations. 6 rats constituted the control group and received m-THPC by means of an intraperitoneal injection. The brains were extracted at 4 h, 24 h and 96 h after Temoporfin injection. The samples were examined with a confocal laser scanning microscope. All samples showed high fluorescence emission exclusively in the tumour area, without appreciable differences between the samples taken at the different times of sacrifice and the two routes of administration. No fluorescence whatsoever was detected among normal brain tissue surrounding the tumour. The intratumoral route appears to give comparable results to the systemic one, regarding intracellular uptake efficiency and tumour--normal tissue ratio, with the advantage of a much shorter time needed to reach optimal intratumoural concentration--that is just four hours from m-THPC injection.

[Acute renal failure after videolaparoscopic surgery: an avoidable complication?]. / L'insufficianza renale acuta postchirurgia laparoscopica: evitabile complicanza?

Videolaparoscopic surgery exposes the abdominal organs to the mechanical effect of pneumoperitoneum at pressure values between 12 and 15 mm Hg, which are considered safe. Nevertheless, experimental data have shown that this pressure range can represent a hemodynamic risk factor as it may induce a decrease in the venous return to the right ventricle, a decrease in cardiac output, and activation of the sympathetic nervous system and renin angiotensin system. We report two cases of acute renal failure that occurred soon after videolaparoscopy in young female patients without any evidence of ongoing renal disease. Patient A was 29 years old and was submitted to videolaparoscopic surgery in a follow-up program after surgical treatment of ovarian cancer; patient B was 15 years old and was submitted to the surgical removal of a monolateral ovarian cyst. In neither of the cases was it necessary to perform hemodialysis. Patient A underwent a renal biopsy under ultrasound guidance; optic microscopy showed only in ra- and extraglomerular capillary congestion. In both cases the acute renal failure resolved completely and the patients where discharged with normal renal function. Taking in to account that normal renal venous pressure levels are around 4 mmHg we think that a) a 15 mmHg pneumoperitoneum may represent a risk factor during videolaparoscopic surgery mainly if the patient's extracellular volume is not properly expanded; b) administration of nonsteroidal anti-inflammatory drugs in order to prevent surgical pain may inhibit vasodilatory prostaglandin availability; c) onset of oliguria during the surgical procedure suggests that extracellular volume expansion is required.

The physiological role of biogenic amines redox reactions in mitochondria. New perspectives in cancer therapy.

In tumours, polyamines and amine oxidases increase as compared to normal tissues. Cytotoxicity induced by bovine serum amine oxidase (BSAO) and spermine is attributed to H2O2 and aldehydes produced by the reaction. Increasing the incubation temperature from 37 to 42 degrees C enhances cytotoxicity in cells exposed to spermine metabolites. The combination BSAO/spermine prevents tumour growth, particularly well if the enzyme has been conjugated with a biocompatible hydrogel polymer. Since the tumour cells release endogenous substrates of BSAO, the administration of spermine is not required. Combination with hyperthermia improves the cytocidal effect of polyamines oxidation products. Our findings show that multidrug resistant (MDR) cells are more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity which induces the generation of intracellular ROS prior to the onset of mitochondrial permeability transition (MPT). It makes this new approach attractive, since the development of MDR is one of the major problems of conventional cancer therapy.

Cationic liposomes, loaded with m-THPC, in photodynamic therapy for malignant glioma.

In this study we investigated the feasibility of mixed liposomes formed by dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) and cationic gemini surfactant (Gemini 1) loaded with the chlorin m-tetrahydroxyphenylchlorin (m-THPC), in photodynamic therapy (PDT) for glioma. To this aim, an in vitro study was carried out by employing various human glioblastoma cell lines (A172, DBTRG, LN229, U118). The following liposomal formulations were tested: (i) DMPC and Gemini 1; (ii) m-THPC in DMPC in the absence or (iii) in the presence of Gemini 1 in the molar ratio 8:2; 7:3, and 6:4. The presence of Gemini 1 significantly increased the intracellular uptake of chlorin in all cell tested although with a different extent: LN229>U118>A172>DBTRG. The cytotoxicity of chlorin-loaded liposomes was then tested by cloning efficiency performed on different cultures, before and after irradiation with laser light at 652nm, at a Fluence Rate of 200mW/s for 100s, with a total Fluence of 20J/cm(-2). In the absence of irradiation, the different liposomal formulations induced a cytotoxicity in less than 30% of glioblastoma cells. On the contrary, irradiation induced total destruction of all cultures treated with m-THPC/DMPC+Gemini 1 in the ratios 8:2, or 7:3, or 6:4.

Evaluation of sequential perfusion with Euro-Collins and Belzer solutions for pancreas preservation in rats.

OBJECTIVE: To investigate the effect of Euro-Collins and Belzer solutions in a sequential preservation of the pancreas. METHODS: Forty-five Wistar-EPM rats were divided into four groups, according to the solution used during preservation: (1) saline solution (SF): animals perfused and preserved with saline solution; (2) Euro-Collins group (C): animals perfused and preserved with Euro-Collins solution; (3) Belzer group (B): animals perfused and preserved with Belzer solution; (4) Euro-Collins/Belzer group (CB): animals perfused with equal parts of Euro-Collins and Belzer solutions sequentially and preserved with Belzer solution. After perfusion, the animals underwent pancreas resection and preservation with the respective substance at 4 degrees C. Amylase was measured in the preservation solution after 12, 24, 36, or 48 hours. Finally, the pancreas was analyzed histologically, and a statistical analysis was performed. RESULTS: Groups SF and C showed the highest amylase levels in the preservation solution during all periods. The levels were higher than in groups C and CB (P = .05). Amylase levels were similar in groups B and CB to 24 hours (P = .05). Histological analysis was significant for analysis of pancreas islet cells and edema. Groups B and CB were histologically similar (P = .001) and different from groups SF and C. CONCLUSION: Sequential perfusion using Euro-Collins and Belzer solutions was effective for pancreas preservation in rats up to 24 hours.

CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma.

Thirty untreated patients, median age 69 years (range 60 - 75 years), with diffuse large B-cell lymphoma (B-DLCL) were treated with a pegylated liposomal doxorubicin (PL-doxorubicin) modified CHOP-rituximab regimen. PL-doxorubicin 30 mg/m2, was given in combination with standard dosage of prednisone, vincristine, cyclophosphamide, rituximab (according to CHOP-R regimen) every 21 days for six courses. Cardiac toxicity was evaluated by mean of echocardiography for left ventricular ejection fraction (LVEF) evaluations and serum troponin-I levels. Overall response and complete response rates were 76% and 59%. Projected two year event free survival and overall survival are 65.5% and 68.5%. No treatment-related mortality was documented. WHO grade III-IV neutropenia and thrombocytopenia were 86% and 3%. Extra-hematological III-IV toxicity was represented, respectively, by a single case of infection, mucositis, and bleeding. LVEF evaluations and the troponin levels did not show significant changes over the course of the treatment. One patient with a previous history of atrial fibrillation experienced a single episode of arrhythmia. None of the patients developed palmar-plantar erythrodysesthesia. This regimen appears an active regimen for the treatment of elderly patients with B-DLCL. The replacement of conventional doxorubicin with PL-doxorubicin seems to be associated with a negligible incidence of extra-hematological toxicity, in particular cardiac and infectious complications.