Search

Sustained lymphocyte migration from blood into lymph nodes (LNs) is important for immune responses. The CC-chemokine receptor-7 (CCR7) ligand CCL21 is required for LN entry but is downregulated during inflammation, and it has been unclear how recruitment is maintained. Here, we show that the oxysterol biosynthetic enzyme cholesterol-25-hydroxylase (Ch25h) is upregulated in LN high endothelial venules during viral infection. Lymphocytes become dependent on oxysterols, generated through a transcellular endothelial-fibroblast metabolic pathway, and the receptor EBI2 for inflamed LN entry. Additionally, Langerhans cells are an oxysterol source. Ch25h is also expressed in inflamed peripheral endothelium, and EBI2 mediates B cell recruitment in a tumor model. Finally, we demonstrate that LN CCL19 is critical in lymphocyte recruitment during inflammation. Thus, our work explains how naive precursor trafficking is sustained in responding LNs, identifies a role for oxysterols in cell recruitment into inflamed tissues, and establishes a logic for the CCR7 two-ligand system., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure and competing interests statement. MI participates in advisory boards/consultantship for Gilead Sciences, Asher Biotherapeutics, GentiBio, BlueJay Therapeutics, and Aligos Therapeutics. The remaining authors declare no competing interests. MI is inventor on patents filed, owned, and managed by Telethon Foundation and San Raffaele Scientific institute on technology related to the work presented here (PCT/EP2020/064933).

G protein-coupled receptors (GPCRs) are vital cell surface receptors that govern a myriad of physiological functions. Despite their crucial role in regulating antitumor immunity and tumorigenesis, therapeutic applications targeting GPCRs in oncology are currently limited. This review offers a focused examination of selected protumorigenic chemokine and metabolite-sensing GPCRs. Specifically, the review highlights five GPCRs able to orchestrate tumor immunobiology at three main levels: tumor immunity, cancer cell expansion, and blood vessel development. The review culminates by illuminating emerging therapies and discussing innovative strategies to harness the full potential of GPCR-targeted treatments, by applying a multireceptor and patient-specific logic., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Reversing CD8 + T cell dysfunction is crucial in treating chronic hepatitis B virus (HBV) infection, yet specific molecular targets remain unclear. Our study analyzed co-signaling receptors during hepatocellular priming and traced the trajectory and fate of dysfunctional HBV-specific CD8 + T cells. Early on, these cells upregulate PD-1, CTLA-4, LAG-3, OX40, 4-1BB, and ICOS. While blocking co-inhibitory receptors had minimal effect, activating 4-1BB and OX40 converted them into antiviral effectors. Prolonged stimulation led to a self-renewing, long-lived, heterogeneous population with a unique transcriptional profile. This includes dysfunctional progenitor/stem-like (T SL ) cells and two distinct dysfunctional tissue-resident memory (T RM ) populations. While 4-1BB expression is ubiquitously maintained, OX40 expression is limited to T SL . In chronic settings, only 4-1BB stimulation conferred antiviral activity. In HBeAg + chronic patients, 4-1BB activation showed the highest potential to rejuvenate dysfunctional CD8 + T cells. Targeting all dysfunctional T cells, rather than only stem-like precursors, holds promise for treating chronic HBV infection., Competing Interests: Declaration of interests M. Iannacone participates in advisory boards/consultantship for Asher Biotherapeutics, GentiBio, BlueJay Therapeutics, and Aligos Therapeutics. L.G.G. participates in boards/consultantship for Genenta Science, Epsilen Bio, Aligos Therapeutics, Medicxi, Chroma Medicine, and Ananda Immunotherapies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The blood-brain barrier (BBB) acquires unique properties to regulate neuronal function during development. The formation of the BBB, which occurs in tandem with angiogenesis, is directed by the Wnt/β-catenin signaling pathway. Yet the exact molecular interplay remains elusive. Our study reveals the G protein-coupled receptor GPR126 as a critical target of canonical Wnt signaling, essential for the development of the BBB's distinctive vascular characteristics and its functional integrity. Endothelial cell-specific deletion of the Gpr126 gene in mice induced aberrant vascular morphogenesis, resulting in disrupted BBB organization. Simultaneously, heightened transcytosis in vitro compromised barrier integrity, resulting in enhanced vascular permeability. Mechanistically, GPR126 enhanced endothelial cell migration, pivotal for angiogenesis, acting through an interaction between LRP1 and β1 integrin, thereby balancing the levels of β1 integrin activation and recycling. Overall, we identified GPR126 as a specifier of an organotypic vascular structure, which sustained angiogenesis and guaranteed the acquisition of the BBB properties during development.

Peyer's patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFβ-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning in the SED are unclear. Here, we found that PP cDC2s express GPR35, a receptor that promotes cell migration in response to various metabolites, including 5-hydroxyindoleacetic acid (5-HIAA). In mice lacking GPR35, fewer cDC2s were found in the SED, and frequencies of IgA + germinal center (GC) B cells were reduced. IgA plasma cells were reduced in both the PPs and lamina propria. These phenotypes were also observed in chimeric mice that lacked GPR35 selectively in cDCs. GPR35 deficiency led to reduced coating of commensal bacteria with IgA and reduced IgA responses to cholera toxin. Mast cells were present in the SED, and mast cell-deficient mice had reduced PP cDC2s and IgA + cells. Ablation of tryptophan hydroxylase 1 (Tph1) in mast cells to prevent their production of 5-HIAA similarly led to reduced PP cDC2s and IgA responses. Thus, mast cell-guided positioning of GPR35 + cDC2s in the PP SED supports induction of intestinal IgA responses.

The bone marrow is the main site of blood cell production in adults, however, rare pools of hematopoietic stem and progenitor cells with self-renewal and differentiation potential have been found in extramedullary organs. The lung is primarily known for its role in gas exchange but has recently been described as a site of blood production in mice. Here, we show that functional hematopoietic precursors reside in the extravascular spaces of the human lung, at a frequency similar to the bone marrow, and are capable of proliferation and engraftment. The organ-specific gene signature of pulmonary and medullary CD34 + hematopoietic progenitors indicates greater baseline activation of immune, megakaryocyte/platelet and erythroid-related pathways in lung progenitors. Spatial transcriptomics mapped blood progenitors in the lung to a vascular-rich alveolar interstitium niche. These results identify the lung as a pool for uniquely programmed blood stem and progenitor cells with the potential to support hematopoiesis in humans., Competing Interests: Declarations The authors declare no competing financial interests.

Neutrophil recruitment from circulation to sites of inflammation is guided by multiple chemoattractant cues emanating from tissue cells, immune cells, and platelets. Here, we focus on the function of one G-protein coupled receptor, GPR35, in neutrophil recruitment. GPR35 has been challenging to study due the description of multiple ligands and G-protein couplings. Recently, we found that GPR35-expressing hematopoietic cells respond to the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). We discuss distinct response profiles of GPR35 to 5-HIAA compared to other ligands. To place the functions of 5-HIAA in context, we summarize the actions of serotonin in vascular biology and leukocyte recruitment. Important sources of serotonin and 5-HIAA are platelets and mast cells. We discuss the dynamics of cell migration into inflamed tissues and how multiple platelet and mast cell-derived mediators, including 5-HIAA, cooperate to promote neutrophil recruitment. Additional actions of GPR35 in tissue physiology are reviewed. Finally, we discuss how clinically approved drugs that modulate serotonin uptake and metabolism may influence 5-HIAA-GPR35 function, and we speculate about broader influences of the GPR35 ligand-receptor system in immunity and disease., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cryptococcus neoformans is the leading cause of fungal meningitis and is characterized by pathogenic eosinophil accumulation in the context of type-2 inflammation. The chemoattractant receptor GPR35 is expressed by granulocytes and promotes their migration to the inflammatory mediator 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. Given the inflammatory nature of cryptococcal infection, we examined the role of GPR35 in the circuitry underlying cell recruitment to the lung. GPR35 deficiency dampened eosinophil recruitment and fungal growth, whereas overexpression promoted eosinophil homing to airways and fungal replication. Activated platelets and mast cells were the sources of GPR35 ligand activity and pharmacological inhibition of serotonin conversion to 5-HIAA, or genetic deficiency in 5-HIAA production by platelets and mast cells resulted in more efficient clearance of Cryptococcus. Thus, the 5-HIAA-GPR35 axis is an eosinophil chemoattractant receptor system that modulates the clearance of a lethal fungal pathogen, with implications for the use of serotonin metabolism inhibitors in the treatment of fungal infections., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Humoral immunity is crucial for protection against invading pathogens. Broadly neutralizing antibodies (bnAbs) provide sterilizing immunity by targeting conserved regions of viral variants and represent the goal of most vaccination approaches. While antibodies can be selected to bind virtually any region of a given antigen, the consistent induction of bnAbs in the context of influenza and HIV has represented a major roadblock. Many possible explanations have been considered; however, none of the arguments proposed to date seem to fully recapitulate the observed counter-selection for broadly protective antibodies. Antibodies can influence antigen presentation by enhancing the processing of CD4 epitopes adjacent to the binding region while suppressing the overlapping ones. We analyze the relative positioning of dominant B and T cell epitopes in published antigens that elicit strong and poor humoral responses. In strong immunogenic antigens, regions bound by immunodominant antibodies are frequently adjacent to CD4 epitopes, potentially boosting their presentation. Conversely, poorly immunogenic regions targeted by bnAbs in HIV and influenza overlap with clusters of dominant CD4 epitopes, potentially conferring an intrinsic disadvantage for bnAb-bearing B cells in germinal centers. Here, we propose the theory of immunodominance relativity, according to which the relative positioning of immunodominant B and CD4 epitopes within a given antigen drives immunodominance. Thus, we suggest that the relative positioning of B-T epitopes may be one additional mechanism that cooperates with other previously described processes to influence immunodominance. If demonstrated, this theory can improve the current understanding of immunodominance, provide a novel explanation for HIV and influenza escape from humoral responses, and pave the way for a new rational design of universal vaccines.

Background: Invasive Meningococcal Disease is a severe disease mainly affecting infants and young children. Most infections are caused by serogroups A, B, C, W, X, and Y. In the last 10 years, serogroup B has been the main cause of Invasive Meningococcal Disease in Europe. Recent data resulting from an observational study conducted in Italy show a significant reduction in the number of Invasive Meningococcal Disease cases due to Neisseria meningitidis B after the introduction of vaccine 4CMenB. Thus, the Naples Team of Federation of Italian Primary Care Pediatricians and the Public Health Department started an active collaboration focused on vaccination process management (named "Progetto Via") with the aim of increasing Meningococcal B vaccination coverage., Study Design: Source of data is the regional platform "GE.VA.". Every Primary care Pediatrician uses daily to record vaccination activity. This platform is integrated with data entered by operators of the District/Vaccination Center., Methods: Time: January 2019 - December 2019. The Federation of Italian Primary Care Pediatricians/Naples organized a meeting to identify six coordinators. The pediatricians could choose to counsel in their own offices and send children to the vaccination center or to counsel and vaccinate directly in their own clinics., Results: A total of 78 pediatricians took part in the project: 46 did only counseling and 32 did both counseling and vaccination in their medical clinic. Data obtained show an overall average vaccination coverage growth of about 13% in the first 4 months of the survey, and a further growth of about 11% in the following seven months, with a total growth in the entire period of 24%. The pediatricians' counseling is essential to recover non-compliant subjects, considering both the relationship of trust with the families and the visits already scheduled as an ideal moment for vaccinations' status check., Conclusions: The project highlights how an effective collaboration between family pediatricians and the Local Health Authority becomes valuable in getting closer to reach the Ministerial goal of 95%. Vaccination coverage increased significantly when family pediatricians supported the activity of vaccine centers in distress in many regional situations. The trust relationship, the hourly availability and the capillary network of family pediatricians' clinics were key elements for the success of this project and were also recognized by parents.

Mediterranean Diet (Med Diet) is one of the healthiest dietary patterns. We aimed to verify the effects of weaning (i.e., the introduction of solid foods in infants previously fed only with milk) using adult foods typical of Med Diet on children eating habits, and on the microbiota composition. A randomized controlled clinical trial on 394 healthy infants randomized in a 1:1 ratio in a Med Diet group weaned with fresh; seasonal and tasty foods of Med Diet and control group predominantly weaned with industrial baby foods. The primary end point was the percentage of children showing a good adherence to Med Diet at 36 months. Secondary end points were mother’s changes in adherence to Med Diet and differences in children gut microbiota. At 36 months, children showing a good adherence to Med Diet were 59.3% in the Med Diet group and 34.3% in the control group (p < 0.001). An increase in adherence to the Med Diet was observed in the mothers of the Med Diet group children (p < 0.001). At 4 years of age children in the Med Diet group had a higher gut microbial diversity and a higher abundance of beneficial taxa. A Mediterranean weaning with adult food may become a strategy for early nutritional education, to develop a healthy microbiota, to prevent inflammatory chronic diseases and to ameliorate eating habits in children and their families.

The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis., Competing Interests: Disclosures:   E. Vivier is an employee of Innate Pharma. C.F. Ware reported grants from Capella Biosciences, grants from Eli Lilly, and grants from Boehringer Ingelheim Pharmaceuticals outside the submitted work; in addition, C.F. Ware had a patent to USP 8,974,787 issued and a patent to USP 8,349,320 issued. No other disclosures were reported., (© 2021 Vanderkerken et al.)

Differentiation of CD4 + T cells into either follicular helper T (T FH ) or type 1 helper T (T H 1) cells influences the balance between humoral and cellular adaptive immunity, but the mechanisms whereby pathogens elicit distinct effector cells are incompletely understood. Here we analyzed the spatiotemporal dynamics of CD4 + T cells during infection with recombinant vesicular stomatitis virus (VSV), which induces early, potent neutralizing antibodies, or recombinant lymphocytic choriomeningitis virus (LCMV), which induces a vigorous cellular response but inefficient neutralizing antibodies, expressing the same T cell epitope. Early exposure of dendritic cells to type I interferon (IFN), which occurred during infection with VSV, induced production of the cytokine IL-6 and drove T FH cell polarization, whereas late exposure to type I IFN, which occurred during infection with LCMV, did not induce IL-6 and allowed differentiation into T H 1 cells. Thus, tight spatiotemporal regulation of type I IFN shapes antiviral CD4 + T cell differentiation and might instruct vaccine design strategies.

Type I interferons (IFNs) released upon viral infections play different and opposing roles in disease outcome. This pleiotropic effect is mainly influenced by the cellular sources, timing and target cells for these molecules. The effect of type I IFN signaling on the activation and differentiation of antiviral CD4 + T cells remains ill defined, with studies reporting either a beneficial or a detrimental role, depending on the context of infection. This review will highlight several recent studies that have investigated the role of type I IFNs in the priming and polarization of CD4 + T cells and discuss areas of uncertainty that require further investigation., (Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Immunoglobulin M (IgM) is the first type of antibody produced during acute infections and thus provides an early line of specific defense against pathogens. Being produced in secondary lymphoid organs, IgM must rapidly be exported to the blood circulation. However, it is currently unknown how such large pentameric molecules are released from lymph nodes (LNs). Here, we show that upon immunization, IgM transiently gains access to the luminal side of the conduit system, a reticular infrastructure enabling fast delivery of tissue-derived soluble substances to the LN parenchyma. Using microinjections of purified IgM, we demonstrate that conduit-associated IgM is delivered by neither the afferent lymph nor the blood, but is locally conveyed by conduits. Exploiting in vivo models, we further demonstrate that conduit-associated IgM is locally and transiently produced by activated, antigen-specific B cells migrating in the T cell zone. Thus, our study reveals that the conduit system is coopted by B cells to rapidly export secreted IgM out of LNs., (© 2018 Thierry et al.)

Viral infections represent a major threat for mankind. The adaptive immune system plays a key role in both viral clearance and disease pathogenesis, and, accordingly, understanding how lymphocytes interact with different viruses is critical to design more effective vaccination and therapeutic strategies. The recent advent of intravital microscopy has enabled the real-time visualization of the complex interplay between viruses and the ensuing adaptive immune response in living organisms. Here, we will review the most significant recent insights on antiviral adaptive immune responses obtained through intravital imaging. We will also discuss what challenges lie ahead and what we think are the most promising areas for future research., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cellular functions are strongly dependent on surrounding cells and environmental factors. Current technologies are limited in their ability to characterize the spatial location and gene programs of cells in poorly structured and dynamic niches. We developed a method, NICHE-seq, that combines photoactivatable fluorescent reporters, two-photon microscopy, and single-cell RNA sequencing (scRNA-seq) to infer the cellular and molecular composition of niches. We applied NICHE-seq to examine the high-order assembly of immune cell networks. NICHE-seq is highly reproducible in spatial tissue reconstruction, enabling identification of rare niche-specific immune subpopulations and gene programs, including natural killer cells within infected B cell follicles and distinct myeloid states in the spleen and tumor. This study establishes NICHE-seq as a broadly applicable method for elucidating high-order spatial organization of cell types and their molecular pathways., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Several lines of evidence indirectly suggest that antigenic stimulation through the B-cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self-antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglobulins expressed in CLL. How pathogen-specific BCRs drive CLL development remains, however, largely unexplored. Here, we utilized mouse models of CLL pathogenesis to equip B cells with virus-specific BCRs and study the effect of antigen recognition on leukemia growth. Our results show that BCR engagement is absolutely required for CLL development. Unexpectedly, however, neither acute nor chronic exposure to virus-derived antigens influenced leukemia progression. Rather, CLL clones preferentially selected light chains that, when paired with virus-specific heavy chains, conferred B cells the ability to recognize a broad range of autoantigens. Taken together, our results suggest that pathogens may drive CLL pathogenesis by selecting and expanding pathogen-specific B cells that cross-react with one or more self-antigens., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)

Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b + Ly6C hi inflammatory monocytes. These myeloid cells were recruited to lymph nodes draining LCMV infection sites in a type I interferon-, CCR2-dependent fashion and they suppressed antiviral B cell responses by virtue of their ability to produce nitric oxide. Depletion of inflammatory monocytes, inhibition of their lymph node recruitment or impairment of their nitric oxide-producing ability enhanced LCMV-specific B cell survival and led to robust neutralizing antibody production. In conclusion, our results identify inflammatory monocytes as critical gatekeepers that prevent antiviral B cell responses and suggest that certain viruses take advantage of these cells to prolong their persistence within the host., Competing Interests: The authors declare that they have no competing interests.

Background: Epidemiologic evidences suggest a strong association between low birth weight and some diseases in adult life ( hypertension, diabetes, cardiovascular diseases).Aim of this study was to evaluate the obesity/overweight prevalence in a population of children born small for gestation age, SGA children 400, 208 males and 192 females compared to a population of children born appropriate for gestational age 6818 AGA children, 3502 males and 3316 females, during childhood. Our intention was also to build the natural history of weight gain during prepubertal age in children born SGA and AGA., Design and Methods: Observational prospective longitudinal study. We followed our patients from January2001 up to December 2010; weight, height and body mass index (BMI) were evaluated in all the SGA and AGA children. BMI z-score range for defining overweight and obesity was, respectively, 1.13 to 1.7 and >1.7 according to CDC growth charts., Results: In transversal evaluation, we prove that 10-year-old SGA females are twice obese and more overweight compared to equal age AGA females. In longitudinal evaluation, we highlight different observations: SGA children obese at 2 years are still obese at 10 years; the number of obese SGA children increases gradually until the age of 10; AGA children, appear to be less obese than SGA children at 10 years., Conclusion: SGA males and females are more obese at 5 and 10 years compared to the AGA population. Primary care pediatricians, through early detection of the children at risk, can carry out an effective obesity prevention project in SGA children., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens, and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4(+) and γδ T cells, neutrophils, or dendritic cells, and their effect does not rely on local macrophage depletion, Toll-like receptor signaling, or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as an additional class of adjuvants that boost humoral immune responses., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to analyze the role of interventional ultrasound in the treatment of nonvascular complications in liver transplant recipients., Methods: Between August 1996 and May 2003, we performed 426 OLTs in 394 patients, 287 men (73%) and 107 women (27%), mean age of 50 +/- 9.5 years (range 17 to 68.2). A total of 2556 diagnostic ultrasound examinations were performed, resulting in a mean of 5.9 per patient (range 2 to 21). The interventional maneuvers included: echo-guided biopsies; drainage of abdominal or thoracic effusions; drainage of abdominal, intrahepatic, or splenic collections; positioning of biliary drains; and use of the "rendezvous" technique., Results: Six hundred seventy-seven echo-guided interventional maneuvers were performed in 394 OTL patients, comprising 417 (61.6%) biopsies and 260 (38.4%) therapeutic maneuvers. Eighty-one ascite drains were positioned (31.1%); in 73 cases, pleural effusions were drained (28.1%). Sixty-seven abdominal or intrahepatic collections were drained (25.8%), of which 36 (53.7%) were due to bilomas or biliary peritonitis, 15 (22.4%) hematomas, 4 (5.9%) hepatic abscesses, 11 (16.4%) infected abdominal collections, and 1 (1.5%) splenic abscess. Thirty-nine cases (15%) of biliary drainage were performed. In 33 cases (7.9%), the parenchymal biopsies were not diagnostic because of an inadequate specimen. The treatment success rate was 96.1%. No complications related to the therapeutic maneuvers were recorded, but there were 5 biopsy-related complications (1.2%)., Conclusions: Echo-guided interventional maneuvers are safe, produce a high success rate, and represent an important option in the management of OLT patients.

We refer our experience about continent ileal orthotopic bladder in male patient with bladder tumor we report our selections criteria, with particular attention about technical point of view. We show the results, early and late complications.

Epidemiology, diagnostics, staging, surgical procedure and survival data of 219 patients with renal cells carcinoma are reported (1970-1990). Diagnosis is based on Tc and angiography. Possibly in the future high sensitivity methods like Magnetic Resonance could limit the use of invasive techniques. 207 patients underwent radical nephrectomy and 68 of these lymphadenectomy too (para and pre aortic and/or caval). In 41 patients the tumor had involved the venous system and 9 cavatomies, 2 caval resections and 1 atriotomy have been performed. In the stage T1-T2-T3 NoMoVo the survival rate (at. 5 years) is 87%, 80%, and 75% respectively. The survival in N+MoVo patients is 17% (at 5 y.) and in V+NoMo patients 57%.

The authors, after mentioning the anatomopathologic, physiopathologic and clinical features of cyrsoid aneurysms, presently classed in the chapter of the congenital artero-venous fistulas, show a case, angiographically discovered, of cyrsoid aneurysm with palmar location, elsewhere already subjected twice to unsuccessful operation, and successfully operated at the Institute of Surgical Pathology of the Pavia University. The Authors think the morphologic and topographic features of such lesion, its relative local malignancy and trend to relapsing, justify why the old denomination of cyrsoid aneurysm was kept, even in the frame of the more general chapter of artero-venous fistulas.