Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic ...mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A “consensus” classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.
The interaction of programmed death-1 (PD-1) on T lymphocytes with its ligands Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) on tumor cells and/or tumor-associated ...macrophages results in inhibitory signals to the T-cell receptor pathway, consequently causing tumor immune escape. PD-L1/PD-L2 are currently used as predictive tissue biomarkers in clinical practice. Virtually PD-L1 levels expressed by tumor cells are associated with a good response to immune checkpoint blockade therapies targeting the PD-1/PD-L1 axis. These therapies restore T-cell antitumor immune response by releasing T-lymphocytes from the inhibitory effects of tumor cells. Immune checkpoint therapies have completely changed the management of patients with solid cancers. This therapeutic strategy is less used in hematological malignancies, although good results have been achieved in some settings, such as refractory/relapsed classic Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Variable results have been obtained in diffuse large B-cell lymphoma and T-cell lymphomas. Immunohistochemistry represents the main technique for assessing PD-L1 expression on tumor cells. This review aims to describe the current knowledge of PD-L1 expression in various types of lymphomas, focusing on the principal mechanisms underlying PD-L1 overexpression, its prognostic significance and practical issues concerning the evaluation of PD-L1 immunohistochemical results in lymphomas.
Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as ...a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.
Primary effusion lymphoma is a rare, aggressive large B-cell lymphoma strictly linked to infection by Human Herpes virus 8/Kaposi sarcoma-associated herpes virus. In its classic form, it is ...characterized by body cavities neoplastic effusions without detectable tumor masses. It often occurs in immunocompromised patients, such as HIV-positive individuals. Primary effusion lymphoma may affect HIV-negative elderly patients from Human Herpes virus 8 endemic regions. So far, rare cases have been reported in transplanted patients. The purpose of our systematic review is to improve our understanding of this type of aggressive lymphoma in the setting of transplantation, focusing on epidemiology, clinical presentation, pathological features, differential diagnosis, treatment and outcome. The role of assessing the viral serological status in donors and recipients is also discussed.
We performed a systematic review adhering to the PRISMA guidelines. The literature search was conducted on PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Cochrane Library, using the search terms "primary effusion lymphoma" and "post-transplant".
Our search identified 13 cases of post-transplant primary effusion lymphoma, predominantly in solid organ transplant recipients (6 kidney, 3 heart, 2 liver and 1 intestine), with only one case after allogenic bone marrow transplantation. Long-term immunosuppression is important in post-transplant primary effusion lymphoma commonly developing several years after transplantation. Kaposi Sarcoma occurred in association with lymphoma in 4 cases of solid organ recipients. The lymphoma showed the classical presentation with body cavity effusions in absence of tumor masses in 10 cases; 2 cases presented as solid masses, lacking effusions and one case as effusions associated with multiple organ involvement. Primary effusion lymphoma occurring in the setting of transplantation was more often Epstein Barr-virus negative. The prognosis was poor. In addition to chemotherapy, reduction of immunosuppressive treatment, was generally attempted.
Primary effusion lymphoma is a rare, but often fatal post-transplant complication. Its rarity and the difficulty in achieving the diagnosis may lead to miss this complication. Clinicians should suspect primary effusion lymphoma in transplanted patients, presenting generally with unexplained body cavity effusions, although rare cases with solid masses are described.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a “consensus” classification has been recently developed to provide a common base for the ...molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.
In this paper, the synthetic inertia need of the small island of Pantelleria in the Mediterranean Sea is assessed. Firstly, the optimal renewable energy mix able to minimize the Levelized Cost of ...Energy for the generation system of the island is evaluated, considering the yearly load demand and the characteristics of the local natural resources. The optimal energy mix introduces in the island a quota of power generation with static power converters interfaced to the grid that could jeopardize the security of the system if not suitably controlled. Therefore, the inherent inertial response of the diesel generators of the system is calculated hour by hour for each month of one year, considering the new schedule of the generators for various cases characterized by different percentages of production from the optimum renewable energy mix. Finally, the rated power and capacity of a battery energy storage system is calculated in order to compensate the reduction of the inertial response in the power system thanks to a suitable synthetic inertia control. The calculation is done by considering the maximum allowed frequency nadir in case of a disturbance. For each scenario, the maximum disturbance is also assessed with and without synthetic inertia. The results are compared with those obtained in a previous study on the same island where batteries were used for different purposes.
•Sizing of a renewable energy mix to cover a share of energy demand in small island.•The best energy mix is given by the minimization of the Levelized Cost of Energy.•Three daily contributions from unprogrammable renewable source are assessed.•The corresponding inertia of the power system is calculated in all scenarios.•A controlled battery energy storage system providing synthetic inertia is needed.
Abstract Introduction Colonic Diverticular Disease (CDD) is a multifactorial inflammatory disease. Acute diverticulitis (AD), with extraluminal free air (both pericolic and distant), represents about ...15% of radiological scenarios and remains a therapeutic challenge for surgeons. Currently, the WSES guidelines suggest trying a conservative strategy both in the presence of pericolic and distant free extraluminal air, even if both have respectively weak recommendation based on low/very low‐quality evidence. Methods We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyzes guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Embase databases were used to identify articles of interest. Results A total of 2380 patients with AD and extraluminal free air (both pericolic and distant) who underwent nonoperative management (NOM) were analyzed. Of the 2380 patients, 2095(88%) were successfully treated with NOM, while 285 (12%) patients failed. A total of 1574 (93.1%) patients with pericolic extraluminal free air had a successful NOM with 6.9% (117) failure rates, while 135 (71.1%) patients with distant extraluminal free air had a successful NOM with 28.9% (55) failure rates. Regarding distant recurrence, we recorded a rate of 18.3% (261/1430), while a rate of 11.3% (167/1472) was recorded for patients undergoing elective surgery. Conclusion NOM for patients with AD and extraluminal free air (both pericolic and distant) seems to be feasible and safe despite a higher failure rate in the distant subgroup, which remains the most challenging clinical scenario to deal with through conservative treatment.
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