32 research outputs found
Immune Microenvironment in Colorectal Cancer: A New Hallmark to Change Old Paradigms
Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells
Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
Background The search for immunological markers
with ability of predicting clinical outcome is a priority in
lymphomas, and in cancer in general. It is well known
that some immunomodulatory cells, such as myeloid
derived suppressor cells (MDSCs) or regulatory T cells
(Tregs), are recruited by tumors, jeopardizing antitumor
immunosurveillance. In this work, we have studied blood
levels of these immunosuppressive cells in patients with
relapsed/refractory diffuse large B-cell lymphoma (R/R
DLBCL), prior to and along the course of the experimental
rituximab, gemcitabine, dexamethasone, and cisplatin (R2-
GDP) schedule, as a translational substudy of the R2-GDP GOTEL trial (EudraCT Number: 2014-001620-29), which
included lenalidomide as an immunomodulator.
Methods Blood samples were taken before treatment,
at cycle 3 and end of induction. Samples were analyzed
by flow cytometry. Non-parametric tests were used.
Mann-Whitney U test was used to compare basal cells
distributions, and Wilcoxon test was considered to
compare cells distribution at different times. Spearman
test was performed to measure the degree of association
between cell populations.
Results In this study, MDSC and Treg circulating
concentration was found increased in all patients
compared with a healthy control group and decreased
after treatment only in patients with longest overall
survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes
expressing Programmed Death-1 (PD-1) were increased
in peripheral blood from patients and decreased on the
treatment, whereas activated T lymphocytes increased
after therapy in those with better overall survival.
Conclusions In conclusion, blood concentration of MDSCs
and Treg cells may be good prognostic markers for overall
survival after 2 years in R/R DLBCL. These results point to a
possible role of these elements in the immunosuppression
of these patients, as assessed by the circulating activated
and inhibited T lymphocytes, and therefore, they may be
considered as therapeutic targets in DLBCL
Experimental study of hybrid-knife endoscopic submucosal dissection (ESD) versus standard ESD in a Western country
BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective but time-consuming treatment for early neoplasia that requires a high level of expertise. OBJECTIVE: The objective of this study was to assess the efficacy and learning curve of gastric ESD with a hybrid knife with high pressure water jet and to compare with standard ESD. MATERIAL AND METHODS: We performed a prospective non survival animal study comparing hybrid-knife and standard gastric ESD. Variables recorded were: Number of en-bloc ESD, number of ESD with all marks included (R0), size of specimens, time and speed of dissection and adverse events. Ten endoscopists performed a total of 50 gastric ESD (30 hybrid-knife and 20 standard). RESULTS: Forty-six (92 %) ESD were en-bloc and 25 (50 %) R0 (hybrid-knife: n = 13, 44 %; standard: n = 16, 80 %; p = 0.04). Hybrid-knife ESD was faster than standard (time: 44.6 +/- 21.4 minutes vs. 68.7 +/- 33.5 minutes; p = 0.009 and velocity: 20.8 +/- 9.2 mm(2)/min vs. 14.3 +/- 9.3 mm(2)/min (p = 0.079). Adverse events were not different. There was no change in speed with any of two techniques (hybrid-knife: From 20.33 +/- 15.68 to 28.18 +/- 20.07 mm(2)/min; p = 0.615 and standard: From 6.4 +/- 0.3 to 19.48 +/- 19.21 mm(2)/min; p = 0.607). The learning curve showed a significant improvement in R0 rate in the hybrid-knife group (from 30 % to 100 %). CONCLUSION: despite the initial performance of hybrid-knife ESD is worse than standard ESD, the learning curve with hybrid knife ESD is short and is associated with a rapid improvement. The introduction of new tools to facilitate ESD should be implemented with caution in order to avoid a negative impact on the results
Small Bowel Enteroscopy - A Joint Clinical Guideline by the Spanish and Portuguese Small-Bowel Study Groups
The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small-bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication, and its diagnostic and therapeutic yield. A set of recommendations was issued accordingly.info:eu-repo/semantics/publishedVersio
Endoscopic Submucosal Dissection. Sociedad Española de Endoscopia Digestiva (SEED) clinical guideline
The reason to write this guideline is to familiarize Spanish endoscopists and gastroenterologists not only with the general indications of the procedure and possible complications but also the dedicated tools
Small bowel enteroscopy - A joint clinical guideline from the spanish and portuguese small bowel study groups
The present evidence-based guidelines are focused on the
use of device-assisted enteroscopy in the management of
small-bowel diseases. A panel of experts selected by the
Spanish and Portuguese small bowel study groups reviewed
the available evidence focusing on the main indications of
this technique, its role in the management algorithm of each
indication and on its diagnostic and therapeutic yields. A set
of recommendations were issued accordingly.Estas recomendações baseadas na evidência detalham o
uso da enteroscopia assistida por dispositivo no manejo
clínico das doenças do intestino delgado. Um conjunto de
Gastrenterologistas diferenciados em patologia do intestino delgado foi selecionado pelos grupos de estudos Espanhol e Português de intestino delgado para rever a evidência disponível sobre as principais indicações desta
técnica, o seu papel nos algoritmos de manejo de cada
indicação e sobre o seu rendimento diagnóstico e terapêutico. Foi gerado um conjunto de recomendações pelos autores
SEOM-GECOD clinical guideline for unknown primary cancer (2021).
Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity
Role of Immune Escape Mechanisms in Hodgkin's Lymphoma Development and Progression: A Whole New World with Therapeutic Implications
Hodgkin's lymphoma represents one of the most frequent lymphoproliferative syndromes, especially in young population. Although HL is considered one of the most curable tumors, a sizeable fraction of patients recur after successful upfront treatment or, less commonly, are primarily resistant. This work tries to summarize the data on clinical, histological, pathological, and biological factors in HL, with special emphasis on the improvement of prognosis and their impact on therapeutical strategies. The recent advances in our understanding of HL biology and immunology show that infiltrated immune cells and cytokines in the tumoral microenvironment may play different functions that seem tightly related with clinical outcomes. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of HL microenvironment. This new knowledge will probably translate into a change in the antineoplastic treatments in HL in the next future and hopefully will increase the curability rates of this disease
Experimental study of hybrid-knife endoscopic submucosal dissection (ESD) versus standard ESD in a Western country
Background: Endoscopic submucosal dissection (ESD) is an effective but time-consuming treatment for early neoplasia that requires a high level of expertise. Objective: The objective of this study was to assess the efficacy and learning curve of gastric ESD with a hybrid knife with high-pressure water jet and to compare with standard ESD. Material and methods: We performed a prospective non-survival animal study comparing hybrid-knife and standard gastric ESD. Variables recorded were: Number of en-bloc ESD, number of ESD with all marks included (R0), size of specimens, time and speed of dissection and adverse events. Ten endoscopists performed a total of 50 gastric ESD (30 hybrid-knife and 20 standard). Results: Forty-six (92%) ESD were en-bloc and 25 (50%) R0 (hybrid-knife: n = 13, 44%; standard: n = 16, 80%; p = 0.04). Hybrid-knife ESD was faster than standard (time: 44.6 ± 21.4 minutes vs. 68.7 ± 33.5 minutes; p = 0.009 and velocity: 20.8 ± 9.2 mm²/min vs. 14.3 ± 9.3 mm²/min (p = 0.079). Adverse events were not different. There was no change in speed with any of two techniques (hybrid-knife: From 20.33 ± 15.68 to 28.18 ± 20.07 mm²/min; p = 0.615 and standard: From 6.4 ± 0.3 to 19.48 ± 19.21 mm²/min; p = 0.607). The learning curve showed a significant improvement in R0 rate in the hybrid-knife group (from 30% to 100%). Conclusion: despite the initial performance of hybrid-knife ESD is worse than standard ESD, the learning curve with hybrid-knife ESD is short and is associated with a rapid improvement. The introduction of new tools to facilitate ESD should be implemented with caution in order to avoid a negative impact on the results
Lenalidomide plus R-GDP (R2-GDP) in Relapsed/ Refractory Diffuse Large B-Cell Lymphoma: Final Results of the R2-GDP-GOTEL Trial and Immune Biomarker Subanalysis
Purpose: New therapeutic options are needed in relapsed/refrac tory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide based schedules can reverse rituximab refractoriness in lymphoma.
Patients and Methods: In the phase II R2-GDP trial, 78
patients unsuitable for autologous stem cell transplant received
treatment with the following schedule: lenalidomide 10 mg Days
(D)1–14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1,
gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg
D1–3, up to 6 cycles (induction phase), followed by lenalidomide
10 mg (or last lenalidomide dose received) D1–21 every 28 days
(maintenance phase). Primary endpoint was overall response
rate (ORR). Secondary endpoints included progression-free
survival (PFS), overall survival (OS), safety, and monitorization
of key circulating immune biomarkers (EU Clinical Trials Reg ister number: EudraCT 2014-001620-29).
Results: After a median follow-up of 37 months, ORR was
60.2% [37.1% complete responses (CR) and 23.1% partial
responses (PR)]. Median OS was 12 months (47 vs. 6 months
in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in
CR vs. no CR). In the primary refractory population, ORR was
45.5% (21.2% CR and 24.3% PR). Most common grade 3–4
adverse events were thrombocytopenia (60.2%), neutropenia
(60.2%), anemia (26.9%), infections (15.3%), and febrile neutro penia (14.1%). Complete responses were associated with a sharp
decrease in circulating myeloid-derived suppressor cells and
regulatory T cells.
Conclusions: R2-GDP schedule is feasible and highly active
in R/R DLBCL, including the primary refractory population.
Immune biomarkers showed differences in responders versus
progressors.Consejería de Salud y Familias. Junta de Andalucí