Microbiological assessment of arterial allografts processed in a tissue bank.

The transmission of microbial infection through tissue allografts is one of the main risks that must be controlled in tissue banks. Therefore, microbiological monitoring controls and validated protocols for the decontamination of tissues during processing have been implemented. This study is based on the evaluation of data from microbiological cultures of arteries (mainly long peripheral arteries) processed in the tissue bank of Valencia (Spain). Donors' profile, pre- and post-disinfection tissue samples were assessed. The presence of residual antibiotics in disinfected tissues was determined and the antimicrobial potential of these tissues was tested. Our overall contamination rate was 23.69%, with a disinfection rate (after antibiotic incubation) of 87.5%. Most (76.09%) of the microbial contaminants were identified as Gram positive. Arterial allografts collected from body sites affected by prior organ removal showed higher risk of contamination. Only vancomycin was detected as tissue release. The antimicrobial effect on Candida albicans was lower than that for bacterial species. Risk assessment for microbial contamination suggested the donor's skin and the environment during tissue collection as the main sources for allograft contamination. Antibiotic-disinfected arterial allografts showed antimicrobial potential.

Structural transition induced by compression and stretching of puckered arsenene nanotubes.

The stretching and compression effects on puckered arsenene nanotubes (AsNTs) are investigated by using density functional calculations. The atomic arrangement determines the nanotube properties and relative stability; therefore, zigzag, chiral, and armchair present different properties. Since the AsNT properties depend on the diameter, three cases are considered: (a) (0, 9) and (9, 0), (b) (0, 14) and (14, 0), and (c) (0, 19) and (19, 0) NTs. For all calculated parameters of the smallest NTs, it is found that the armchair (0, 9) nanotube is always more stable than the zigzag (9, 0) nanotube. On the other hand, for the two largest NTs, a structural transition from armchair to zigzag is found upon stretching. Phase transitions are of great interest, in part because they result in changes of the properties of the material under study, changes that can be used in many technologies. To our knowledge, this is the first time that a structural transition in a puckered nanotube has been predicted. Our results show that the electronic band gap of the AsNTs can be modulated by increasing or decreasing the axial lattice parameter. It is also found that semiconductor NTs are more stable than metallic NTs.

Myeloablative versus reduced intensity allogeneic stem cell transplantation for relapsed/refractory Hodgkin's lymphoma in recent years: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years. PATIENTS AND METHODS: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study. RESULTS: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC. Relapse rate (RR) was somewhat lower in the MAC group (41% versus 52% at 24 months, P = 0.16). This lower RR translated into a marginal improvement in event-free survival (EFS) for the MAC group (48% versus 36% at 24 months, P = 0.09) with no significant differences in overall survival (73% for MAC and 62% for RIC at 24 months, P = 0.13). Multivariate analysis after adjusting for disease status at the time of allo-SCT showed that the use of MAC was of borderline statistical significance for predicting a lower RR and EFS [HR 0.7, 95% CI (0.5-1.0), P = 0.1] and [HR 0.7, 95% CI (0.5-1.0), P = 0.07], respectively, after allo-SCT. CONCLUSIONS: With modern transplant practices, the NRM associated with MAC for HL has strongly decreased, resulting into non-significant improvement of EFS because of a somewhat better disease control compared with RIC transplants. The intensity of conditioning regimens should be considered when designing individual allo-SCT strategies or clinical trials in patients with relapsed/refractory HL.

A short CD3/CD28 costimulation combined with IL-21 enhance the generation of human memory stem T cells for adoptive immunotherapy.

BACKGROUND: Immunotherapy based on the adoptive transfer of gene modified T cells is an emerging approach for the induction of tumor-specific immune responses. Memory stem T cells, due to their enhanced antitumor and self-renewal capacity, have become potential candidate for adoptive T cell therapy of cancer. Methods to generate memory stem T cells ex vivo rely on CD3/CD28 costimulation and the use of cytokines such as IL-7 and IL-15 during the entire culture period. However, a strong costimulation may induce differentiation of memory stem T cells to effector memory T cells. Here we show that manipulation of the length of the costimulation and addition of IL-21 enhance the ex vivo expansion of memory stem T cells. METHODS: Purified naïve T cells from healthy donors were cultured in the presence of anti-CD3/CD28 coated beads, IL-7, IL-15 and/or IL-21 (25 ng/ml). T cells phenotype from the different memory and effector subpopulations were analyzed by multiparametric flow cytometry. RESULTS: A short anti-CD3/CD28 costimulation of naïve T cells, combined with IL-7 and IL-15 significantly increased the frequencies of CD4(+) and CD8(+) memory stem T cells ex vivo, compared to a prolonged costimulation (34.6 ± 4.4 % vs 15.6 ± 4.24 % in CD4(+); p = 0.008, and 20.5 ± 4.00 % vs 7.7 ± 2.53 % in CD8(+); p = 0.02). Moreover, the addition of IL-21 to this condition further enhanced the enrichment and expansion of CD4(+) and CD8(+) memory stem T cells with an increase in the absolute numbers (0.7 × 10(6) ± 0.1 vs 0.26 × 10(6) ± 0.1 cells for CD4(+); p = 0.002 and 1.1 × 10(6) ± 0.1 vs 0.27 × 10(6) ± 0.1 cells for CD8(+); p = 0.0002; short + IL-21 vs long). CONCLUSIONS: These new in vitro conditions increase the frequencies and expansion of memory stem T cells and may have relevant clinical implications for the generation of this memory T cell subset for adoptive cell therapy of patients with cancer.

Chiral phosphorus nanotubes: structure, bonding, and electronic properties.

The study of black phosphorus nanotubes (PNTs) had been devoted to zigzag and armchair structures, with no consideration of chiral structures to date. In this communication, we studied the structural and electronic (band structure) properties of chiral nanotubes using a periodic plane wave-pseudopotential approach. We found that some chiral nanotubes display similar bandgaps and binding energies per atom (BEA) as armchair PNTs and Born-Oppenheimer molecular dynamics (BOMD) calculations attest their thermal stability. Interestingly, we determined that the bandgap is tuned by varying the PNTs chirality and it is not related to their diameters. This feature can be exploited in optical and electronic applications wherein a direct and sizable bandgap is required.

Doped penta-graphene and hydrogenation of its related structures: a structural and electronic DFT-D study.

The structure of penta-graphene (penta-C), an irregular pentagonal two-dimensional (2D) structure, has been predicted recently. In this communication we carried out a dispersion-corrected density functional theory (DFT-D) study of the penta-C doped with Si, Ge and Sn atoms and its related hydrogenated penta-C structures (H-penta-C-X). We predict various new structures as thermally stable based on Born-Oppenheimer molecular dynamics (BOMD) calculations. Moreover, their dynamical stability is attested by phonon dispersions spectra. In general, we found that the bandgap value of doped structures reduces, while H-penta-C-X show large bandgap values. This feature can be exploited for potential uses of hydrogenated doped-penta-C structures as dielectric layers in electronic devices.

Vegetation exerts a greater control on litter decomposition than climate warming in peatlands.

Historically, slow decomposition rates have resulted in the accumulation of large amounts of carbon in northern peatlands. Both climate warming and vegetation change can alter rates of decomposition, and hence affect rates of atmospheric CO2 exchange, with consequences for climate change feedbacks. Although warming and vegetation change are happening concurrently, little is known about their relative and interactive effects on decomposition processes. To test the effects of warming and vegetation change on decomposition rates, we placed litter of three dominant species (Calluna vulgaris, Eriophorum vaginatum, Hypnum jutlandicum) into a peatland field experiment that combined warming.with plant functional group removals, and measured mass loss over two years. To identify potential mechanisms behind effects, we also measured nutrient cycling and soil biota. We found that plant functional group removals exerted a stronger control over short-term litter decomposition than did approximately 1 degrees C warming, and that the plant removal effect depended on litter species identity. Specifically, rates of litter decomposition were faster when shrubs were removed from the plant community, and these effects were strongest for graminoid and bryophyte litter. Plant functional group removals also had strong effects on soil biota and nutrient cycling associated with decomposition, whereby shrub removal had cascading effects on soil fungal community composition, increased enchytraeid abundance, and increased rates of N mineralization. Our findings demonstrate that, in addition to litter quality, changes in vegetation composition play a significant role in regulating short-term litter decomposition and belowground communities in peatland, and that these impacts can be greater than moderate warming effects. Our findings, albeit from a relatively short-term study, highlight the need to consider both vegetation change and its impacts below ground alongside climatic effects when predicting future decomposition rates and carbon storage in peatlands.

Prostatectomy pathology findings in an active surveillance population.

OBJECTIVES: The difficulty in predicting indolent prostate cancer leads to the use of different inclusion criteria in an active surveillance (AS) program. This chapter presents the pathology findings of radical prostatectomy (RP) in patients whose disease meet criteria for AS, as well as of those who are operated during AS. METHODS: Two independent Medline searches were conducted, both of them with a double objective: pathological findingsin radical prostatectomy specimens of patients who could have been included in AS and pathological features of patients operated after an AS period. The following terms were used for the research: "prostaticneoplasm", "radical prostatectomy" and "active surveillance": "radical prostatectomy", "after", "following" and "active surveillance". Pathological findings in radical prostatectomy specimens, down staging and downgrading rates were recorded. Active surveillance length and reason for surgery was included when it was available. RESULTS: Depending on different AS inclusion criteria, clinical downgrading rate (pathological Gleason > 6) varied between 12.1 and 61% and clinical downstaging between 0-26%. Pathological Gleason score =8 was reported in 0-7.8% and there were anecdotal findings of seminal vesicle invasion or positive nodes. Overall, unfavorable pathology (Gleason ≥ 7 or stage ≥ pT3)was detected in 13.1-42.4%, based on different definitions. The criteria at John Hopkins were the strictest and had the lowest clinical downgrading and downstaging. On the other hand, the Memorial Sloan Kettering Cancer Center(MSKCC) criteria had the highest risk of unfavorable pathology but had the highest recruitment capacity. Indolent tumor was observed in 70-82.2% according to the current definition. The average duration in AS prior to surgery was 15-37 months. pT3 stage was seen in 7.7-36.7%, Gleason score 3+4 in 18.6-42.9%, Gleason score 4+3 in 1.4-31.8%, Gleason score >7 in 0-10.3%, positive margins in 3-40.9%. Seminal vesicle invasion rate was extremely low (0-2.9%) as well as positive nodes (0-4.5%). CONCLUSIONS: Although there is a low risk of clinical downstaging and downgrading between patients who have being included in AS, it remains feasible. The probability of predicting an indolent tumor depends greatly on the quality of the prostate biopsy and/or the confirmatory biopsy. On the other hand, most patients who progress in an AS program can have a high probability of cure. We are still in the early stages of AS management in order to be able to predict the biological behavior and the cure rate of radical prostatectomy in patients after a long AS period.

[Non-invasive diagnosis of prostate cancer: serum and urine markers]. / Diagnóstico no invasivo del cáncer de próstata; marcadores séricos y en orina.

The great number of biomarkers basic research is presenting in different clinical scenarios of prostate cancer demands the scientific community rigor in their molecular and clinical development for the selection of those which could supply diagnostic and prognostic information for the established nomograms of clinical-pathological factors. Prostate cancer, due to its prevalence and heterogeneity, needs a more directed diagnosis, characterization of malignant potential and monitoring of its multiple therapies. In this review article we try to go over the recent incorporation of new serum and urine markers in the clinical management of this tumor, emphasizing those with greater clinical development.

Stereotactic body radiation therapy in patients with metachronous oligorecurrent prostate cancer: A single-center experience.

INTRODUCTION AND OBJECTIVE: Metachronous oligorecurrence in prostate cancer (PCa) occurs in patients with localized disease who, after failed radical treatment, develop oligometastases. Metastasis-directed stereotactic radiotherapy (SBRT) aims to delay androgen deprivation therapy. In this study, we report our experience to elucidate the role of SBRT in a selected population of patients with metachronous oligorecurrence. MATERIAL AND METHODS: Retrospective analysis of patients treated with SBRT for oligorecurrent PCa between November 2015 and December 2020. We detailed clinicopathological characteristics at disease onset (age, PSA, stage, primary treatment), clinical scenario at diagnosis of oligorecurrence (PSA, PSA velocity, metastases characteristics), progression-free survival, castration resistance-free survival, dose, and toxicity of SBRT. RESULTS: Thirty-eight SBRT treatments were applied to 13 lymph node and 25 bone metastases in a total of 28 patients. After a follow-up of 34.57 months (21.17-57.59), 17 patients had radiological progression of the disease and 11 presented castration resistant PCa. PFS and CRFS were 21.93 and 44.13 months, respectively. Only 2 patients presented grade 1 toxicity. CONCLUSIONS: In patients with metachronous oligorecurrent PCa, SBRT constitutes a safe and effective treatment that allows delaying the onset of androgen deprivation therapy and the time to castration resistance, assuming low levels of toxicity.

A single-center comparison of our initial experiences in treating penile and urethral cancer with video-endoscopic inguinal lymphadenectomy (VEIL) and later experiences in melanoma cases.

Background: Video-endoscopic inguinal lymphadenectomy (VEIL) is a minimally invasive approach that is increasingly indicated in oncological settings, with mounting evidence for its long-term oncological safety. Objectives: To present our single-center experience of treating penile and urethral cancer with VEIL, as well as its more recent application in melanoma patients. Methods: We prospectively recorded our experiences with VEIL from September 2010 to July 2018, registering the patient primary indication, surgical details, complications, and follow-up. Results: Twenty-nine patients were operated in one (24) or both (5) groins; 18 had penile cancer, 1 had urethral cancer, and 10 had melanoma. A mean 8.62 ± 4.45 lymph nodes were removed using VEIL and of these, an average of 1.00 ± 2.87 were metastatic; 16 patients developed lymphocele and 10 presented some degree of lymphedema; there were no skin or other major complications. The median follow-up was 19.35 months; there were 3 penile cancer patient recurrences in the VEIL-operated side. None of the melanoma patients presented a lymphatic inguinal recurrence. Conclusions: VEIL is a minimally invasive technique which appears to be oncologically safe showing fewer complications than open surgery. However, complications such as lymphorrhea, lymphocele, or lymphedema were not diminished by using VEIL.

Patients with a failed renal transplant.

Despite the advances in the care of recipients and in immunosuppression, long-term graft survival has experienced little improvement in the last 10 years. An important number of recipients present progressive loss of graft function and have to be readmitted on dialysis therapy. Before starting dialysis, these patients are re-exposed to the complications of chronic renal failure but there are no specific guidelines for their treatment. The Kidney Disease Quality Initiative Advisory Board clinical practice guidelines given for the non-transplant chronic kidney disease patients have been recommended for ameliorating their clinical situation and the rate of progression of graft failure. The time when dialysis has to be restarted and the type of dialysis procedure, hemodialysis or peritoneal dialysis, are under discusion. But there is no evidence about the superiority of either type of dialysis procedure. Systematic graft nephrectomy has been considered to improve the inflammatory status of the patients with a failed graft which could contribute to a worse control of some complications such as anemia and to the increased rates of cardiovascular mortality. As in the patients with primary end-stage renal disease, retransplantation is the best treatment for a patient with a failed graft. Due to the shortage of organs for transplantation the number of patients who are retransplanted has remained stable. Recurrent diseases such as glomerulonephritis, lyphoproliferative diseases, BK virus nephopathy and previous non-adherence to the treatment do not necessarily preclude retransplantation.

Update and optimization of active surveillance in prostate cancer in 2021. / Actualización y optimización de la vigilancia activa en cáncer de próstata en 2021.

INTRODUCTION AND OBJECTIVES: Within the paradigm shift of the last decade in the management of prostate cancer (PCa), perhaps the most relevant event has been the emergence of active surveillance (AS) as a mandatory strategy in low-risk disease. We carry out a critical review of the clinical, pathological and radiological improvements that allow optimizing AS in 2021. MATERIAL AND METHODS: Critical narrative review of the literature on improvement issues and controversial aspects of AS. RESULTS: Adequate use of traditional criteria, optimized by enhanced biopsy and calculation of the prostate volume technique thanks to multiparametric magnetic resonance imaging (mpMRI) allow a better selection of patients for AS. This management should not be limited to patients under 60years of age, and patients with intermediate-risk PCa should be carefully selected to be included. Biopsies are still required in the follow-up, which can be personalized according to risk patterns. The pathologist must identify the cribriform or intraductal histology on biopsies in order to exclude these patients from AS, in the same way as with patients with alterations in DNA repair genes. CONCLUSIONS: Controversial indications such as the inclusion of patients from intermediate-risk groups, or the transition to active treatment due to exclusive progression in tumor volume, should be further optimized. It is possible that the future competition of tissue biomarkers, the refinement of objective parameters of mpMRI and the validation of PSA kinetics calculators may sub-stratify risk groups.

Seroconversion and Abundance of IgG Antibodies against S1-RBD of SARS-CoV-2 and Neutralizing Activity in the Chilean Population.

COVID-19 is a pandemic caused by SARS-CoV-2. In Chile, half a million people have been infected and more than 16,000 have died from COVID-19. As part of the clinical trial NCT04384588, we quantified IgG against S1-RBD of SARS-CoV-2 (anti-RBD) in recovered people in Santiago and evaluated their suitability as COVID-19 convalescent plasma donors. ELISA and a luminescent SARS-CoV-2 pseudotype were used for IgG and neutralizing antibody quantification. 72.9% of the convalescent population (468 of 639) showed seroconversion (5-55 µg/mL anti-RBD IgG) and were suitable candidates for plasma donation. Analysis by gender, age, and days after symptom offset did not show significant differences. Neutralizing activity correlated with an increased concentration of anti-RBD IgG (p < 0.0001) and showed a high variability between donors. We confirmed that the majority of the Chilean patients have developed anti-SARS-CoV-2 antibodies. The quantification of anti-RBD IgG in convalescent plasma donors is necessary to increase the detection of neutralizing antibodies.

Does active surveillance avoid overtreatment in prostate cancer? Lessons learned from salvage radical prostatectomies.

OBJECTIVE: Determine whether our institution´s active surveillance (AS) protocol is a suitable strategy to minimise prostate cancer overtreatment. MATERIAL AND METHODS: Retrospective analysis of 516 patients on AS after prostate cancer diagnosis. Population divided into "per-protocol" vs "induced" AS depending on fulfilment of protocol´s inclusion criteria. Radical prostatectomies after AS were selected and stratified based on: reclassification, progression or patient anxiety. Clinicopathological features and biochemical relapse-free survival were studied. Primary endpoint was overtreatment ratio based on the presence of insignificant prostate cancer and adverse pathological features in the surgical specimen. Kaplan-Meier curves were used to estimate the biochemical relapse-free survival and compared with log-rank test. RESULTS: 304 patients fulfilled inclusion criteria; 100 proceeded to radical prostatectomy (31% "induced", 69% "per-protocol" AS). Surgery indications were reclassification, progression and anxiety in 66%, 18% and 16% of patients respectively. Rate of positive lymph nodes was higher in the progression group (11%) compared to reclassification and anxiety (5% and 0% respectively, P = .002). Positive surgical margins were more frequently reported in the progression cohort compared to reclassification (28% vs 20%). Median follow-up from diagnosis until last radical prostatectomy was 48.3 months (32.4-70). 3 year biochemical relapse-free survival in the salvage radical prostatectomy was 85.4% (95 CI 78.3-93.2). Insignificant cancer was noticed in 7% of patients (Epstein´s vs 24% Wolters´ criteria). Rate of patients with adverse pathological features was 36%. CONCLUSIONS: The majority of patients who underwent salvage surgery after AS were not overtreated. Radical prostatectomy should be considered a safe rescue treatment.

Role of PCA3 and SelectMDx in the optimization of active surveillance in prostate cancer.

INTRODUCTION & OBJECTIVES: A not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program. MATERIALS & METHODS: Prospective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined. RESULTS: SelectMDx showed statistically significant differences related to PPFS (HR 1.035, 95%CI: 1.012-1.057) (p = 0.002) with a C-index of 0.670 (95%CI: 0.529-0.810) and AUC of 0.714 (95%CI: 0.603-0.825) at 5 years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95%CI: 0.455-0.805). CONCLUSIONS: In the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.

Clinical drivers for imaging testing in non-metastatic castration-resistant prostate cancer in clinical practice: Results of the IDENTIFICA study. / Factores clínicos determinantes para la realización de pruebas de imagen en cáncer de próstata resistente a la castración no metastásico en la práctica clínica: resultados del estudio IDENTIFICA.

INTRODUCTION: The aim of the study was to describe the clinical drivers that lead physicians to perform imaging tests in search of metastasis in non-metastasic castration prostate resistant cancer (nmCRPC) patients. METHODS: Observational, cross-sectional study conducted at the Departments of Urology of 38 Spanish hospitals. The study included 188 patients diagnosed with nmCRPC who underwent an imaging test for the assessment of metástasis. In one study visit, physicians were requested to specify the clinical factors that led them to perform these tests. The results of the imaging tests and the clinical characteristics of the patients since the time of prostate cancer (PC) diagnosis, were reported. Regression analyses were used to determine predictors of imaging test results. RESULTS: Prostate-specific antigen (PSA) level was the most important driver to order imaging tests (57.1%), followed by regular follow-up (16.5%) and PSA doubling time (PSADT) (12.0%). Although these drivers were not associated to detection of metastasis, patients with PSA levels ≥20 ng/mL had a greater risk of metastasis than patients with PSA levels <4ng/mL (P=.004) and CRPC patients diagnosed with metastasis (mCRPC) had higher median PSA levels (20.9; interquartile range [IQR]: 6.7-38.6) than nmCRPC (9.1; IQR: 5.0-18.0) (P=.005). Sixty-six percent of the patients did not undergo any imaging test after CRPC diagnosis until the study visit (10.6, IQR: 4.0-19.5 months). Curative-intent treatment at PC diagnosis and Gleason score predicted longer time from PC to CRPC diagnosis. CONCLUSIONS: Physicians based their decisions to order imaging tests for metastasis detection in nmCRPC patients mainly on PSA and PSA kinetics, including the regular follow-up stated by guideline recommendations.

Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response.

Fusion of dendritic cells and tumor cells (FCs) constitutes a promising tool for generating an antitumor response because of their capacity to present tumor antigens and provide appropriate costimulatory signals. CD40-CD40L interaction has an important role in the maturation and survival of dendritic cells and provides critical help for T-cell priming. In this study, we sought to improve the effectiveness of FC vaccines in a murine model of B-cell lymphoma by engineering FCs to express CD40L by means of an adenovirus encoding CD40L (Adv-CD40L). Before transduction with Adv-CD40L, no CD40L expression was detected in FCs, DCs or tumor cells. The surface expression of CD40L in FC transduced with Adv-CD40L (FC-CD40L) ranged between 50 and 60%. FC-CD40L showed an enhanced expression of CD80, CD86, CD54 and MHC class II molecules and elicited a strong in vitro immune response in a syngeneic mixed lymphocyte reaction. Furthermore, FC-CD40L showed enhanced migration to secondary lymphoid organs. Splenocytes from mice treated with FC-CD40L had a dramatic increase in the production of IL-17, IL-6 and IFN-gamma, compared with controls. Treatment with the FC-CD40L vaccine induced regression of established tumors and increased survival. Our data demonstrate that FC transduced with Adv-CD40L enhances the antitumor effect of FC vaccines in a murine lymphoma model and this is associated with an increased Th17-type immune response.

Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial.

BACKGROUND: To evaluate the activity and safety of nonpegylated liposomal doxorubicin (Myocet) when substituted for doxorubicin in the R-CHOP regimen (R-COMP). PATIENTS AND METHODS: Seventy-five elderly patients with diffuse large B-cell lymphoma (DLBCL) were studied. Only patients with left ventricular ejection fraction (LVEF) > or =50% were allowed. R-COMP regimen was administered every 3 weeks for three cycles, followed by additional five cycles in case of complete response (CR) or partial response. RESULTS: From November 2002 to April 2005, 75 patients were registered, of which 72 were evaluated. Median age was 72 years (range 61-83); 56% of patients had high or high-intermediate International Prognostic Index score. Median LVEF at baseline was 61%. Thirty-eight patients had history of abnormal cardiovascular conditions. The overall response rate was 71%, with a CR rate of 57%. After a median follow-up of 33 months, the 3-year overall survival, failure-free survival, and progression-free survival rates were 72%, 39%, and 69%, respectively. Neutropenia (54%) was the most frequent grade 3-4 adverse event (AE); 21% of patients experienced cardiac AEs, graded as 3-4 in 4% of the cases. CONCLUSION: R-COMP is an effective regimen for the treatment of DLBCL in elderly patients, with an acceptable tolerability profile.

The relationship between inguinal hernia and minimally-invasive surgery for prostate cancer: A systematic review of the literature. / La relación entre hernia inguinal y cirugía mínimamente invasiva para el cáncer de próstata: revisión sistemática de la literatura.

OBJECTIVE: We aimed to perform a systematic review about the relationship between inguinal hernia and surgery for prostate cancer. BACKGROUND: Diagnosis of abdominal wall defects and prostate cancer may be either synchronous or metachronous. The convenience and safety of combined prostatectomy and hernioplasty, the incidence of hernias after prostatectomy and the feasibility of prostatectomy in patients with previous laparoscopic hernioplasty are still debated. METHODS: PubMed and Embase were queried by dedicated search strings. Two researchers independently reviewed the pooled references and selected the articles of interest, including reviews. RESULTS: Sixty-five studies were evaluated, 22 of them analysed the feasibility and the outcomes of a combined surgery, namely one-stage radical prostatectomy and herniorrhaphy or hernioplasty. Literature evidences support the combined intervention to patients suffering from an inguinal hernia and a prostate cancer amenable of radical prostatectomy. Sixteen studies addressing the potential increase in the occurrence of inguinal hernia after radical prostatectomy were evaluated. Approximately 15% of patients who undergo retro-pubic radical prostatectomy will develop inguinal hernia. It is suggested that the incidence might be lower in laparoscopic prostatectomy series, particularly in case of transperitoneal approach. The median time to the appearance of the hernia is around 6 months. After evaluation of 14 studies, it is concluded that laparoscopic hernioplasty does not preclude prostatectomy but hinders further pelvic surgery. CONCLUSIONS: One-stage combined hernioplasty and radical prostatectomy may be accepted except in cases of lymph-nodes dissection and/or positive hydro-distress test of the urethro-vesical anastomosis. Accurate patient's counselling and dedicated consent form are mandatory, in the setting of an experienced multidisciplinary team.