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D-dimer levels are elevated in COVID 19 and they correlate to the levels of other inflammatory markers such us ferritin, fibrinogen and C-reactive protein. It may be possible to correct D-dimer value in function of inflammatory markers, thus identifying patients at higher risk of venous thromboembolism (VTE). Our objectives are estimating a corrected value of plasma D-dimer as a linear function of ferritin, C-reactive protein and fibrinogen and stablishing a cut-off point of high probability of VTE.Age and sex matched case-control study of all patients diagnosed with COVID 19 and VTE between March and May 2020 in a tertiary hospital in Madrid (Spain). Using linear regression, the best predictive model will be estimated and residual D-dimer values will be obtained and analyzed using ROC curves to determine its discriminative performance.Thirty-eight cases and seventy-six controls were included. There was 63.2% of men and mean age was 68.2. D-dimer was best predicted by a linear model including fibrinogen, ferritin and C-reactive protein. Using residual values, the optimal cutoff point was 2165 ng/mL, with a sensitivity of 57.9% and specificity of 98.7%.It is possible to estimate a D-dimer corrected value in function of ferritin, C-reactive protein and fibrinogen. Using the observed and estimated value we can obtain a residual value that performs well as a screening method to detect patients who would benefit for further VTE diagnostic testing.El dímero-D está elevado en la COVID-19 y se correlacionan con los niveles de otros marcadores inflamatorios como ferritina, fibrinógeno y proteína C reactiva. Cabe la posibilidad de corregir el dímero-D en función de dichos marcadores inflamatorios, identificando así los pacientes con mayor riesgo de enfermedad tromboembólica venosa (ETV). Nuestros objetivos son estimar un valor corregido de dímero-D como función lineal de ferritina, proteína C reactiva y fibrinógeno, y establecer un punto de corte de alta probabilidad de ETV.Estudio de casos y controles emparejados por sexo y edad de todos los pacientes diagnosticados con COVID-19 y ETV entre marzo y mayo de 2020 en un hospital terciario de Madrid, España. Mediante regresión lineal, se estima el mejor modelo predictivo y se obtiene el valor residual de dímero-D. Este se analizará con curvas ROC para determinar su capacidad discriminativa.Se incluyeron 38 casos y 76 controles. Había un 63,2% de varones y la edad media fue de 68,2 años. El valor de dímero-D fue predicho por un modelo que incluyó fibrinógeno, ferritina y proteína C reactiva. Usando los valores residuales, el punto de corte óptimo estimado de 2.165 ng/ml, con una sensibilidad del 57,9% y una especificidad del 98,7%.Es posible estimar un valor corregido de dímero-D en función de ferritina, fibrinógeno y proteína C reactiva. Usando el valor observado y estimado podemos obtener un valor residual que funciona bien como método de cribado para detectar pacientes que podrían beneficiarse de más estudios diagnósticos de la ETV.

Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia. The process was enabled by a shared curation platform, PanelApp, and resulted in the identification and review of 2,144 discordant gene ratings, demonstrating the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.

Background and objective The utility of lung ultrasound as a prognostic tool for patients with acute heart failure is well known, but most studies have been conducted in mixed groups of patients with preserved and reduced ejection fraction. While some subgroup analysis suggests that lung ultrasound is useful regardless of ejection fraction, no specific studies have addressed this question. Our objective is to determine the utility of bedside lung ultrasound as a prognostic tool for patients with preserved ejection fraction, acute heart failure. Material and methods Prospective cohort study with 3-month follow-up after bedside lung ultrasound before discharge in patients hospitalized for acute heart failure with preserved ejection fraction. The number of B lines was determined. Two groups were formed: less than fifteen B lines (unexposed) and fifteen B lines or more (exposed). They were compared in terms of readmission and death attributable to worsening heart failure. Results The exposed group was at higher risk of readmission (HR 2.39, 95% CI 1.12–5.12, P = .024), even after multivariable adjustment (HR 2.46, 95% CI 1.11–5.46, P = .03). Differences between groups in terms of mortality were not statistically significant (HR 1.28, 95% CI .23–6.98). Conclusion Subclinical congestion evaluated with lung ultrasound before discharge is associated with worse prognosis in patients with acute heart failure and preserved ejection fraction. Patients with 15 B lines are 2.5 times more likely to be readmitted for acute heart failure than less congestive patients.

BACKGROUND: Repeat expansion disorders affect about 1 in 3000 individuals and are clinically heterogeneous diseases caused by expansions of short tandem DNA repeats. Genetic testing is often locus-specific, resulting in underdiagnosis of people who have atypical clinical presentations, especially in paediatric patients without a previous positive family history. Whole genome sequencing is increasingly used as a first-line test for other rare genetic disorders, and we aimed to assess its performance in the diagnosis of patients with neurological repeat expansion disorders.METHODS: We retrospectively assessed the diagnostic accuracy of whole genome sequencing to detect the most common repeat expansion loci associated with neurological outcomes (AR, ATN1, ATXN1, ATXN2, ATXN3, ATXN7, C9orf72, CACNA1A, DMPK, FMR1, FXN, HTT, and TBP) using samples obtained within the National Health Service in England from patients who were suspected of having neurological disorders; previous PCR test results were used as the reference standard. The clinical accuracy of whole genome sequencing to detect repeat expansions was prospectively examined in previously genetically tested and undiagnosed patients recruited in 2013-17 to the 100 000 Genomes Project in the UK, who were suspected of having a genetic neurological disorder (familial or early-onset forms of ataxia, neuropathy, spastic paraplegia, dementia, motor neuron disease, parkinsonian movement disorders, intellectual disability, or neuromuscular disorders). If a repeat expansion call was made using whole genome sequencing, PCR was used to confirm the result.FINDINGS: The diagnostic accuracy of whole genome sequencing to detect repeat expansions was evaluated against 793 PCR tests previously performed within the NHS from 404 patients. Whole genome sequencing correctly classified 215 of 221 expanded alleles and 1316 of 1321 non-expanded alleles, showing 97·3% sensitivity (95% CI 94·2-99·0) and 99·6% specificity (99·1-99·9) across the 13 disease-associated loci when compared with PCR test results. In samples from 11 631 patients in the 100 000 Genomes Project, whole genome sequencing identified 81 repeat expansions, which were also tested by PCR: 68 were confirmed as repeat expansions in the full pathogenic range, 11 were non-pathogenic intermediate expansions or premutations, and two were non-expanded repeats (16% false discovery rate).INTERPRETATION: In our study, whole genome sequencing for the detection of repeat expansions showed high sensitivity and specificity, and it led to identification of neurological repeat expansion disorders in previously undiagnosed patients. These findings support implementation of whole genome sequencing in clinical laboratories for diagnosis of patients who have a neurological presentation consistent with a repeat expansion disorder.FUNDING: Medical Research Council, Department of Health and Social Care, National Health Service England, National Institute for Health Research, and Illumina.

Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiotherapy (RT) is the cornerstone of locoregional treatment of non-disseminated disease and the association of chemotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy and patients may achieve a long survival time.

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

Purpose: New therapeutic options are needed in relapsed/refractory 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 Register 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 neutropenia (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.

PURPOSE Nivolumab, an anti–programmed death-1 monoclonal antibody, has demonstrated frequent and durable responses in relapsed/refractory classic Hodgkin lymphoma (cHL). We report results from Cohort D of the CheckMate 205 trial, which assessed nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) for newly diagnosed cHL. METHODS Patients 18 years of age or older with untreated, advanced-stage (defined as III to IV and IIB with unfavorable risk factors) cHL were eligible for Cohort D of this multicenter, noncomparative, phase II trial. Patients received nivolumab monotherapy for four doses, followed by 12 doses of N-AVD; all doses were every 2 weeks, and nivolumab was administered at 240 mg intravenously. The primary end point was safety. Efficacy end points included objective response rate and modified progression-free survival, defined as time to disease progression/relapse, death, or next therapy. Chromosome 9p24.1 alterations and programmed death-ligand 1 expression were assessed in Hodgkin Reed-Sternberg cells in evaluable patients. RESULTS A total of 51 patients were enrolled and treated. At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater. Overall, 59% experienced a grade 3 to 4 treatment-related adverse event. Treatment-related febrile neutropenia was reported in 10% of patients. Endocrine immune-mediated adverse events were all grade 1 to 2 and did not require high-dose corticosteroids; all nonendocrine immune-mediated adverse events resolved (most commonly, rash; 5.9%). At the end of therapy, the objective response rate (95% CI) per independent radiology review committee was 84% (71% to 93%), with 67% (52% to 79%), achieving complete remission (five patients [10%] were nonevaluable and counted as nonresponders). With a minimum follow-up of 9.4 months, 9-month modified progression-free survival was 92%. Patients with higher-level Hodgkin Reed-Sternberg programmed death-ligand 1 expression had more favorable responses to N-AVD ( P = .041). CONCLUSION Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype. The histological transformation (HT) of FL is an event considered frequent in the natural history of this tumor. We studied the transformation rates, predictive factors, and treatment characteristics that may impact in the survival of patients with FL and HT. A total of 1074 patients diagnosed with FL were prospectively enrolled from 1990 to 2016 in a Spanish registry. Sixty-four HTs were recorded based on clinical criteria (55%) or histological confirmation (45%). The cumulative incidence rate of transformation at 5 years is 7.3%. The 5-year overall survival (OS) without HT was 85% (95% confidence interval [CI], 70%-90%) vs 66% (95% CI, 51%-76%; P = 0.0012) with HT. Factors associated with HT were elevated lactate dehydrogenase (LDH) (odds ratio [OR] 1.83), intermediate-high Follicular lymphoma international prognostic index (FLIPI) (OR 2.16-OR 3.21), B symptoms (OR 2.46), or Eastern Cooperative Oncology Group (ECOG) 1 (OR 2.35). Treatment options related to HT were "watch and wait" or no rituximab or anthracyclines initially. A 5-year OS for patients treated with chemotherapy before HT was 55% (95% CI, 38%-69%) versus 81% (95% CI, 53%-93%; P = 0.009) for those who had not received it. The HT rate has decreased after the introduction of rituximab, as has been previously described. The timing of this treatment had an impact on the survival of these patients.

Gut microbiome (GM) and its either pro-tumorigenic or anti-tumorigenic role is intriguing and constitutes an evolving landscape in translational oncology. It has been suggested that these microorganisms may be involved in carcinogenesis, cancer treatment response and resistance, as well as predisposition to adverse effects. In melanoma patients, one of the most immunogenic cancers, immune checkpoint inhibitors (ICI) and MAPK-targeted therapy—BRAF/MEK inhibitors—have revolutionized prognosis, and the study of the microbiome as a modulating factor is thus appealing. Although BRAF/MEK inhibitors constitute one of the main backbones of treatment in melanoma, little is known about their impact on GM and how this might correlate with immune re-induction. On the contrary, ICI and their relationship to GM has become an interesting field of research due to the already-known impact of immunotherapy in modulating the immune system. Immune reprogramming in the tumor microenvironment has been established as one of the main targets of microbiome, since it can induce immunosuppressive phenotypes, promote inflammatory responses or conduct anti-tumor responses. As a result, ongoing clinical trials are evaluating the role of fecal microbiota transplant (FMT), as well as the impact of using dietary supplements, antibiotics and probiotics in the prediction of response to therapy. In this review, we provide an overview of GM’s link to cancer, its relationship with the immune system and how this may impact response to treatments in melanoma patients. We also discuss insights about novel therapeutic approaches including FMT, changes in diet and use of probiotics, prebiotics and symbiotics. Finally, we hypothesize on the possible pathways through which GM may impact anti-tumor efficacy in melanoma patients treated with targeted therapy, an appealing subject of which little is known.

Up to 25% of patients with classical Hodgkin lymphoma (cHL) and a negative interim PET/CT will progress. Unfortunately, there are few published studies on the predictive value of PET/CT performed after finishing treatment. The objective of our study was to assess the role of the final PET/CT (fPET/CT) in predicting progression in a retrospective series of patients treated in the last 10 years with a homogeneous protocol (ABVD + / − radiotherapy). We reviewed a cohort of 227 patients with newly diagnosed cHL. fPET/CT was performed on 212 patients (93%). In patients with a positive fPET, progression-free survival at 60 months was 17% (94% if fPET was negative, p = 0.000). The positive and negative predictive values for the fPET were 76% and 94%, respectively (Fisher’s exact test, p = 0.000). In the subgroup of patients with advanced-stage cHL, progression-free survival at 60 months was 91% with negative fPET and 0% with positive fPET (p = 0.000). However, fPET was negative in 19 of the 29 patients with a positive interim PET/CT (only 2 showed progression). In conclusion, fPET is a useful tool to predict treatment failure in patients with newly diagnosed cHL, especially advanced-stage disease.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.

Background Patients with cancer frequently experience malnutrition, which is associated with higher rates of morbidity and mortality. Therefore, the implementation of strategies for its early detection and for intervention should improve the evolution of these patients. Our study aim is to design and implement a protocol for outpatients starting chemotherapy, by means of which any malnutrition can be identified and treated at an early stage. Methods Before starting chemotherapy for patients with cancer, a complete assessment was made of their nutritional status, using the Nutriscore screening tool. When nutritional risk was detected, an interventional protocol was applied. Results Of 234 patients included in the study group, 84 (36%) required an individualised nutritional approach: 27 (32.1%) presented high nutritional risk, 12 had a Nutriscore result ≥ 5 and 45 experienced weight loss during chemotherapy. Among this population, the mean weight loss (with respect to normal weight) on inclusion in the study was − 3.6% ±8.2. By the end of the chemotherapy, the mean weight gain was 0% ±7.3 (p

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0–1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8–8.1). The median PFS was 5.3 months (95% CI 3.2–7.3), and OS was 9.7 months (95% CI 7.6–11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0–1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00–€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0–1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) and represents ∼35% of all NHLs. In the United States there are estimated to be 3.18 cases per 100,000 populations per ...

Purpose The delayed diagnosis of colorectal cancer (CRC) may be attributable to sociodemographic characteristics, to aspects of tumour histopathology or to the functioning of the health system. We seek to determine which of these factors most influences prolonged patient-attributable delay (PPAD) in the diagnosis and treatment of CRC. Materials and methods A prospective, multicentre observational study was conducted in 22 Spanish hospitals. In total, 1,785 patients were recruited to the study between 2010 and 2012 and underwent elective or urgent surgery. PPAD is considered to occur when the time elapsed between a patient presenting the symptom and him/her seeking attention from the primary care physician or hospital emergency department exceeds 180 days. A bivariate analysis was performed to assess differences in variables segmented by tumour location and patient delay. Multivariate logistic regression analysis was performed on the outcome variable, PPAD. Results The rate of PPAD among this population was 12.1%. PPAD was significantly associated with altered bowel rhythm (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.02 to 1.83) and with adenocarcinoma histology, in comparison with mucinous adenocarcinoma (OR, 2.03; 95% CI, 1.11 to 3.71). Other sociocultural factors and clinicopathological features were not independent predictors of PPAD. Conclusion Many patients do not consider altered bowel rhythm an alarming symptom, warranting a visit to the doctor. PPAD could be reduced by improving health education, raising awareness of CRC-related symptoms.

Head and neck squamous cell carcinoma (HNSCC) is the sixth cancer on incidence worldwide. Tobacco and alcohol consumption are the most classical risk factors associated with its development. Autophagy process has a dual effect both in tumourigenesis and tumour suppressing activity. To investigate the importance of this pathway in HNSCC susceptibility, a risk factor matched case-control association study was performed with four candidate polymorphisms in autophagy genes (ATG2B, ATG5, ATG10, ATG16L1). We found an association between the variant in ATG10 rs1864183 and a higher susceptibility to develop laryngeal cancer, ATG2B rs3759601 and pharyngeal cancer and ATG16L1 rs2241880 and oral carcinoma. ATG5 rs2245214 SNP was not associated with any location. Overall, our results indicate the importance of the autophagy pathway in the susceptibility of head and neck squamous cell carcinoma and demonstrate the heterogeneity between its locations encompassed under a single terminology., Tis study was supported by the health research program of the “Instituto de Salud Carlos III” (PI11/00519, PI13/01741 and PIE14/00066) co fnanced with FEDER founds and for the Health Regional Management of the Junta de Castilla y León (GRS630/A11). J. Fernández-Mateos was partially supported by a predoctoral research grant from the Consejería de Educación—Junta de Castilla y León and the European Social Fund to CC-B (EDU/1084/2012).

[Purpose]: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice., [Materials and methods]: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan–Meier method, was performed, and association with various independent variables was assessed using Cox regression., [Results]: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P, [Conclusion]: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Among the prognostic factors relevant to the condition of oncological patients, nutritional status (NS) has the greatest single impact on quality of life (QL). The goals of our study were to evaluate the influence of NS, weight loss (WL), and the presence of cachexia, prior to the initiation of chemotherapy, on the patient’s QL. Adult patients (aged ≥ 18 years) diagnosed with solid tumours for whom chemotherapy was started between April 2016 and June 2017 were eligible for inclusion in the study. They were asked to complete a QL questionnaire (Functional Assessment of Cancer Treatment (FACT-G)) at the beginning. The presence or absence of cachexia was evaluated at the outset, following the definition proposed by Fearon and nutritional assessment by the Patient-Generated Subjective Global Assessment (PG-SGA) scale. A total of 177 patients completed the FACT-G, the 60% receiving curative therapy. At the start of the treatment, 58.2% of patients had experienced WL, with an average of 4.4 ± 7.4%, and 19% were at risk of malnutrition. Patient who presented cachexia at diagnosis, were treated with palliative intention, had a Nutriscore ≥ 5 points or presented malnutrition in accordance with PG-SGA had a poorer QL (p

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

Early identification of germline BRCA1/2 mutations may be relevant for the management of patients with prostate cancer (PC) and to prevent future breast and ovarian cancers in their relatives. Several prediction tools have been developed to estimate the likelihood of a germline BRCA1/2 mutation and are widely used to optimize screening in breast and ovarian cancer patients. We aimed to elucidate the proportion of PC patients with known BRCA1/2 mutations who would have qualified for testing using two risk calculation models (BRCAPRO and the Manchester scoring system [MSS]). We analyzed 106 families with known BRCA1/BRCA2 mutations, including 23 with PC cases. Only 30% and 48% of PC patients who were known BRCA1/BRCA2 mutations carriers would have qualified for testing using BRCAPRO and MSS, respectively. A median of two breast and/or ovarian cancer cases per family had occurred between the first PC identified in a carrier and the cancer case leading to germline testing. Patient summary We tested two models developed to predict the probability of inherited BRCA1/BRCA2 mutations and found that these tools underperform in men with prostate cancer and should not be used to optimize testing in this population.

We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling technique; Ki-67 antigen, as a cell proliferation marker and density of microvessels (as a marker of angiogenesis). An increase in the percentage of cellular apoptosis is significantly related to the presence of poorly differentiated tumours, with vascular invasion (p

espanolObjeto: el objetivo del presente estudio es examinar la asociacion entre el tipo de admision hospitalaria, la supervivencia y las caracteristicas patologicas de una amplia poblacion de pacientes con cancer colorrectal. Metodos: realizamos un estudio en 1.079 pacientes diagnosticados en el Hospital Costa del Sol de Marbella con cancer colorrectal y evaluamos la relacion entre su tasa de supervivencia y la via por la que realizaron el primer contacto con el hospital (admision programada o de urgencias). Las variables incluidas en nuestro estudio fueron las siguientes: edad, genero, localizacion del tumor, estadio patologico, grado de diferenciacion, quimioterapia previa a la cirugia y supervivencia. Resultados: los pacientes admitidos por primera vez al hospital a traves del Servicio de Urgencias fueron diagnosticados con mayor frecuencia de cancer de colon (63,7%) y con tumores pobremente diferenciados (64,2%) y metastasicos (70%). En el analisis de regresion de Cox la supervivencia libre de enfermedad produjo una razon de riesgo (RR) de 1,36 (intervalo de confianza [IC] 95%: 1,11-1,66) para los pacientes del Servicio de Urgencias y para la supervivencia global de 1,41 (IC 95%: 1,14-1-76). Conclusiones: La admision hospitalaria a traves del Servicio de Urgencias es un indicador de agresividad y de peor pronostico frente a los pacientes que ingresan por via programada EnglishAims: the aim of this study was to examine the possible association between the type of hospital admission and subsequent survival of the patient, as well as the pathological features recorded in a large population of patients with colorectal cancer. Methods: the study included 1,079 patients diagnosed with colon or rectal cancer in the Hospital Costa del Sol (Marbella, Spain). The relationship between patient survival rate and type of first admission to the hospital (elective or emergency admission) was assessed. The following variables were studied: age, gender, tumor location, pathological stage, differentiation grade, chemotherapy before surgery and survival. Results: colon tumors are more common in patients admitted to hospital for the first time via the emergency service (63.7%) and the tumors tend to be poorly differentiated (64.2%) and metastatic (70%). These patients also present a more aggressive disease and a poorer prognosis than patients with an elective admission. With regard to patients from the Emergency Department, a Cox regression analysis showed a risk-ratio (RR) of 1.36 (confidence interval [CI] 95%: 1.11-1.66) for disease-free survival and of 1.41 (95% CI: 1.14-1.76) for overall survival. Conclusions: hospital admission via the Emergency Department is an indicator of aggressiveness and poorer prognosis compared to patients who enter via programmed routes.

Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B, GNA13 and POU2AF1, which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo-diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2, DTX1, UBE2A and HIST1H1E. The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation.

Breast cancer is one of the most common diseases, affecting many thousands of women. Although more than 80% of women survive the experience, very few studies have been conducted to examine the question of resilience among long-term survivors of breast cancer. The aim of this study is to describe the clinical and sociodemographic factors that correlate with greater resilience in women survivors of breast cancer, in the Costa del Sol Health Area (Spain). Accordingly, a descriptive cross-sectional study was conducted, with respect to 59 survivors of breast cancer, who each completed a questionnaire for analysis according to the Connor-Davidson Resilience Scale (CD-RISC). The median resilience score was 77 (interquartile range 70–80). The group of patients who had survived for six or more years since the diagnosis had a higher score for total resilience (90: IR 76–92) than those diagnosed more recently (74: IR 65.7–83.7) (p = 0.012). Regarding the patients’ education background, the group with no formal qualifications or only primary studies had a score of 72 (IR 64–84), versus 79 (IR 74–89.7) for the group with higher levels of education (p = 0.016). Of the clinical variables, only the administration of chemotherapy was significantly associated with the score obtained on the CD-RISC scale (p = 0.012). The results obtained in this study lead us to conclude that sociodemographic and clinical factors have a positive impact on the level of resilience among women resident in the Costa del Sol Health Area and who are long-term survivors of breast cancer.

In this study, we compared eighteen clinical strains of A. baumannii belonging to the ST-2 clone and isolated from patients in the same intensive care unit (ICU) in 2000 (9 strains referred to collectively as Ab_GEIH-2000) and 2010 (9 strains referred to collectively as Ab_GEIH-2010), during the GEIH-REIPI project (Umbrella BioProject PRJNA422585). We observed two main molecular differences between the Ab_GEIH-2010 and the Ab_GEIH-2000 collections, acquired over the course of the decade long sampling interval and involving the mobilome: i) a plasmid harbouring genes for blaOXA 24/40 ss-lactamase and abKA/abkB proteins of a toxin-antitoxin system; and ii) two temperate bacteriophages, Ab105-1varphi (63 proteins) and Ab105-2varphi (93 proteins), containing important viral defence proteins. Moreover, all Ab_GEIH-2010 strains contained a Quorum functional network of Quorum Sensing (QS) and Quorum Quenching (QQ) mechanisms, including a new QQ enzyme, AidA, which acts as a bacterial defence mechanism against the exogenous 3-oxo-C12-HSL. Interestingly, the infective capacity of the bacteriophages isolated in this study (Ab105-1varphi and Ab105-2varphi) was higher in the Ab_GEIH-2010 strains (carrying a functional Quorum network) than in the Ab_GEIH-2000 strains (carrying a deficient Quorum network), in which the bacteriophages showed little or no infectivity. This is the first study about the evolution of the Quorum network and the mobilome in clinical strains of Acinetobacter baumannii during a decade.

Axillary lymph nodes status is the most important prognosis factor in early breast cancer. This status is known by a selective sentinel lymph node biopsy (SLNB) and/or lymphadenectomy. Immunohistochemical studies of breast cancer tumour tissue have reported a relation between the increased expression of vascular endothelial growth factor-C (VEGF-C) and the risk of lymph node metastasis. We researched whether serum levels of VEGF-C could be a predictor factor of sentinel lymph node status in these patients. A prospective analysis was performed on serum from 174 patients with early breast cancer who underwent SLNB. The level of VEGF-C was determined by enzyme-linked immunosorbent assay. Clinical-pathologic variables were collected. Univariate analysis and multivariate logistic regression were conducted, taking SLNB positivity as the segmentation variable. The predictive value of VEGF-C was assessed using ROC curves. Of the sample group of 167 patients, 64 (38.3 %) had affected lymph node. Eighteen patients (28.1 %) presented micrometastasis; there were isolated tumour cells in 11 cases (17.2 %) and macrometastasis in 35 (54.6 %). The median value of VEGF-C was 6561.5 pg/ml. These values did not correlate with any clinical variables, and there was no association between the level of VEGF-C and SLNB status (p = 0.626). In the multivariate analysis, tumour size (p = 0.009) and the presence of vascular invasion (p

Small RNA research is a rapidly growing field. Apart from microRNAs, which are important regulators of gene expression, other types of functional small RNA molecules have been reported in animals and plants. MicroRNAs are important in host-microbe interactions and parasite microRNAs might modulate the innate immunity of the host. Furthermore, small RNAs can be detected in bodily fluids making them attractive non-invasive biomarker candidates. Given the general broad interest in small RNAs, and in particular microRNAs, a large number of bioinformatics aided analysis types are needed by the scientific community. To facilitate integrated sRNA research, we developed sRNAtoolbox, a set of independent but interconnected tools for expression profiling from high-throughput sequencing data, consensus differential expression, target gene prediction, visual exploration in a genome context as a function of read length, gene list analysis and blast search of unmapped reads. All tools can be used independently or for the exploration and downstream analysis of sRNAbench results. Workflows like the prediction of consensus target genes of parasite microRNAs in the host followed by the detection of enriched pathways can be easily established. The web-interface interconnecting all these tools is available at http://bioinfo5.ugr.es/srnatoolbox.

Background. Relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after autologous stem cell transplantation (ASCT) remains a challenge. For these patients treatments with different mechanisms of action rather than classical chemotherapy are needed. Patients and methods. Patients with R/R cHL after ASCT were recruited in a phase II trial (EUDRA CT: 2009-016588-12). Lenalidomide was administered at 20 mg/day for 21 days and cyclophosphamide at 50 mg/day for 28 days (cycles every 28 days). Dose escalation for lenalidomide was permitted. In 2009 we considered that this treatment would be promising if response rate were over 60% and a Simon two-stage binomial design was used to calculate the sample size. A total of 46 patients were planned but the trial would be stopped if less than seven responses after four cycles were obtained in the first 16 patients. Results. The trial was closed early because only five responses were observed after four cycles in the first 16 patients included. Median age was 34 years (18-77). The median number of previous lines was five (2-6). At inclusion, 10 patients were primary refractory and 11 refractory to the last therapy. A total of 110 cycles were administered, with grade >= 3 toxicity in 43 cycles (39%). One non-neutropenic patient developed septic shock resulting in death. An ORR of 38% (1 CR and 5 PR) was observed and a total of 10 patients (62%) achieved clinical benefit. Median progression free survival and overall survival were seven and 19 months, respectively. With a median follow-up of 19 months (3-38+), three-year progression-free and overall survival were 6% and 31%, respectively. Conclusion. The optimistic assumptions of this trial led to an early closure. However, the promising clinical benefit observed with the oral combination of lenalidomide and metronomic cyclophosphamide may justify its use for outpatient palliative treatment.

We performed three different studies to obtain additional data on the biological and prognostic role of vascular endothelial growth factor C (VEGFC) in classical Hodgkin lymphoma (cHL): (1) serum VEGFC levels were measured by enzyme-linked immunosorbent assay in 80 patients; (2) immunohistochemical VEGFC expression in tumor tissue was evaluated using a case-control study in 62 patients; (3) gene expression of VEGFC was investigated in vitro in six cHL cell lines, and was compared with expression in inflammatory lymph nodes. Higher serum VEGFC levels were found in patients with cHL than in healthy volunteers (median, 7675 vs. 1358 pg/mL, p < 0.001) and high VEGFC expression in tissue predicted worse progression-free survival at 7 years (41% vs. 91%, p < 0.0001). VEGFC expression in all Hodgkin lymphoma cell lines was higher than the mean expression level in inflammatory lymph nodes. Our data suggest that Hodgkin and Reed-Sternberg cells produce VEGFC, and VEGFC expression could be a novel prognostic factor in cHL.

Objectives Malnutrition is frequent in patients with cancer and is associated with a higher rate of morbidity and mortality. However, a significant number of patients at nutritional risk remain undetected due to the lack of a routine screening procedure during diagnosis. Costa del Sol Hospital in Marbella (Malaga), Spain has implemented a protocol for outpatients with cancer aimed at identifying and treating malnutrition at an early stage. The aim of this study was to determine the prevalence of nutritional risk and the rate of malnutrition when cancer is diagnosed. Methods We conducted a complete assessment of the nutritional status of patients with cancer of the upper digestive tract (esophagus, stomach, pancreas, or biliary tract) or head and neck cancer. Using the Nutriscore tool at the first oncology consultation, a screening for nutritional risk was performed for patients with other solid tumors. When nutritional risk was detected, a complete nutritional assessment was conducted. Results Of 295 consecutive patients, 21.4% were found to be at nutritional risk (Nutriscore ≥5). After complete assessment, a moderate degree of malnutrition was observed in 76% and severe malnutrition in 12%. Among patients with colorectal cancer or tumors of gynecologic origin, only 7.5% presented nutritional risk, but 52.8% presented cachexia. Conclusion The high rate of malnutrition observed and the identification of cachexia at an early stage highlight the importance of obtaining early identification of patients at risk to improve the efficacy of nutritional interventions.

We examined real-world data on management of relapsed/refractory Hodgkin lymphoma (R/R HL) in five European countries and the consistency of these data with guideline recommendations. Retrospective clinical and epidemiologic data for 509 patients with R/R HL treated between January 2014 and March 2015 were collected at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was 46.3 years; 73.3% were receiving second-line therapy for a first relapse during the reporting period. Most patients received ABVD as front-line chemotherapy, except in Germany where escalated BEACOPP was used more often. The proportion of patients receiving stem cell transplantation (SCT) was 44%; 85% of transplants occurred at first relapse. Brentuximab vedotin (BV) was usually administered after autologous SCT, and was initiated for 65% of patients following SCT failure. Our findings suggest that R/R HL management across these countries is broadly consistent with guideline recommendations and that BV is well-integrated into treatment pathways.

Head and neck cancer (HNC) is defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2013 publication, Spanish Society of Medical Oncology (SEOM) presents an update of HNC diagnosis and treatment guideline. The eighth edition of TNM classification, published in January 2017, introduces important changes for p16-positive oropharyngeal tumours, for lip and oral cavity cancer and for N3 category. In addition, there are new data about induction chemotherapy and the role of immunotherapy in HNC.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma. Patients and methods A total of 1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were prospectively enrolled from 1980 to 2013. Results Median follow-up was 54.9 months and median overall survival is over 20 years in our series. We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group. Out of 166 patients who are still alive after more than 10 years of follow-up, 118 of them (73%) are free of evident clinical disease. Variables significantly associated with survival at 10 years were stage < II (p < 0.03), age < 60 years (p < 0.0001), low FLIPI (p < 0.002), normal 2 microglobulin (p < 0.005), no B symptoms upon diagnosis (p < 0.02), Performance Status 0-1 (p < 0.03) and treatment with anthracyclines and rituximab (p < 0.001), or rituximab (p < 0.0001). Conclusions A longer follow-up and a large series demonstrated a substantial population of patients with follicular lymphoma free of disease for more than 10 years.

High-throughput sequencing (HTS) data for small RNAs (noncoding RNA molecules that are 20-250 nucleotides in length) can now be routinely generated by minimally equipped wet laboratories; however, the bottleneck in HTS-based research has shifted now to the analysis of such huge amount of data. One of the reasons is that many analysis types require a Linux environment but computers, system administrators, and bioinformaticians suppose additional costs that often cannot be afforded by small to mid-sized groups or laboratories. Web servers are an alternative that can be used if the data is not subjected to privacy issues (what very often is an important issue with medical data). However, in any case they are less flexible than stand-alone programs limiting the number of workflows and analysis types that can be carried out.We show in this protocol how virtual machines can be used to overcome those problems and limitations. sRNAtoolboxVM is a virtual machine that can be executed on all common operating systems through virtualization programs like VirtualBox or VMware, providing the user with a high number of preinstalled programs like sRNAbench for small RNA analysis without the need to maintain additional servers and/or operating systems.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease entity. Young patients with high-intermediate and high aa-IPI score seem to be good candidates to receive alternative treatments to standard RCHOP-21 including EPOCH-R,2 R-ACVBP+HDT-ASCT3 and upfront autologous stem cell transplantation. Other risk factors can be used to identify patients for the use of more doseintense regimens including bulky disease, interim PET positivity and, importantly, molecular profiles.

Angiogenesis has substantial prognostic significance in a variety of lymphoid malignancies [1]. Vascular endothelial growth factor-A (VEGF-A) mediates angiogenesis in both physiological and patholo...

Summary Introduction The addition of cetuximab to weekly paclitaxel has demonstrated high efficacy in the first-line treatment of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). However, this combination has been widely extended to patients who present resistance to first line chemotherapy (CT) or those who are not candidates for platinum-based CT. Material and methods We have retrospectively analyzed the efficacy and safety of cetuximab in combination with weekly paclitaxel in patients with R/M-SCCHN who present disease progression after platinum schedules or those who were not candidates for platinum-based CT. Patients received weekly paclitaxel 80 mg/m 2 and cetuximab 250 mg/m 2 (initial dose of 400 mg/m 2 ) until progression or unacceptable toxicity. Results Twenty-two patients were included. Median age was 58 (43–68), ECOG PS (0/1/2): 6/10/4, 19 patients had received prior platinum-based treatment (nine patients were platinum-sensitive and nine were platinum-refractory). With a median follow-up of 6.18 months (range 1.3–29.7), overall response rate (ORR) was 55% (95% CI 31–76%):1 (5%) complete response and 9 (50%) partial responses. Median duration of response was 10.23 months. Median progression free survival (PFS) and overall survival (OS) were 5.4 and 9.1 months, respectively. There were no differences in response rate according to platinum sensitivity (66% sensitive vs 44% refractory; P = 0.61). The main toxicity consisted of rash in 70% of patients (5% grade 3), with an association between rash severity and ORR (grade 0–1: 33% vs grade 2–3: 64%; P = 0.03) and a trend for better PFS and OS. Conclusion Weekly paclitaxel in combination with cetuximab is a well tolerated and highly active second-line treatment in patients with R/MSCCHN who experience disease progression after platinum-based CT, including those who present resistant disease. Our results suggest that the efficacy of this combination is apparently superior than the published data on single agent cetuximab in this setting.

High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic data for key reference projects in a clean, fast and integrated fashion. HGVA provides an efficient and intuitive web-interface for easy data mining, a comprehensive RESTful API and client libraries in Python, Java and JavaScript for fast programmatic access to its knowledge base. HGVA calculates population frequencies for these projects and enriches their data with variant annotation provided by CellBase, a rich and fast annotation solution. HGVA serves as a proof-of-concept of the genome analysis developments being carried out by the University of Cambridge together with UK's 100 000 genomes project and the National Institute for Health Research BioResource Rare-Diseases, in particular, deploying open-source for Computational Biology (OpenCB) software platform for storing and analyzing massive genomic datasets.

Relatively few studies have analyzed the mortality of follicular lymphoma (FL) patients in comparison with a sex- and age-matched general population. This study analyzed the overall survival (OS) of patients with FL and compared their survival with the expected survival of a general population.Patients diagnosed with FL were prospectively enrolled from 1980 to 2013. Standardized mortality ratios (SMRs) were obtained from yearly sex- and age-specific mortality rates in Spain, and OS was compared with age- and sex-matched general population data.A total of 1074 patients with newly diagnosed FL were enrolled. The median OS was 231 months (95% confidence interval [CI], 195-267 months). Event-free survival at 12 months (EFS12) and event-free survival at 24 months (EFS24) were associated with an increased probability of early death, with an SMR of 10.27 (95% CI, 8.26-12.77) for EFS12. The overall SMR, including all causes of death, was 2.55 (95% CI, 2.23-2.92), and it was higher for women (SMR, 3.02; 95% CI, 2.48-3.67) and young adults (SMR, 6.01; 95% CI, 3.13-11.55). More than 10 years after the diagnosis, mortality rates for FL patients were lower than those for the general population (SMR, 0.47; 95% CI, 0.28-0.78). When FL was excluded as a cause of death, the overall SMR was 1.35 (95% CI, 1.11-1.65) without a statistically significant mortality increase in the60-year-old group in comparison with age- and sex-matched general population data. More than 15% of the patients included in the study (n = 158) had more than 10 years of follow-up.EFS12 and EFS24 predict an early increase in mortality. The long-term SMR, over the course of 10 years of follow-up, shows that patients with FL have a risk of dying similar to that of a sex- and age-matched general population. Cancer 2017;123:3709-3716. © 2017 American Cancer Society.

Differences between men and women in the incidence and biological mechanisms of colorectal cancer (CRC) suggest that estrogens may play a role in the pathogenesis of this disease. The identification of the human estrogen receptor beta (ERβ) and its expression in the intestinal mucosa led to further studies that revealed that estrogens have a protective function against CRC mediated by the activation of ERβ. However, ERβ expression and its role in CRC is controversial. The purpose of this study was to determine the distribution and prognostic value of ERβ expression in the intestinal mucosa of patients diagnosed and surgically treated for CRC, and its association with other known prognostic factors. A total of 109 paraffin-embedded samples of the wild-type ERβ isoform were analyzed by immunohistochemical nuclear staining in patients with colorectal adenocarcinoma. Clinical/pathological and survival data were collected. Immunohistochemical quantification was performed using the category scoring system, which has been validated for assessing estrogen receptor alfa. The wild-type ERβ isoform –also called ERβ1– was positive in 101 patients (92.7%) and negative in nine patients (7.3%). Univariate analysis revealed that the absence of expression of the ERβ1 gene was correlated with mucinous adenocarcinoma (p

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the time of diagnosis. They have very poor prognosis.

Aim of the study The authors analyse the effect of chemotherapy on the use of additional health-care resources and report the clinical and demographic factors associated with such use. Patients and methods In women with breast cancer, eligible to receive first-line (neo)-adjuvant or palliative chemotherapy, consultations with health-care practitioners (general practitioners [GPs] and specialists) and admissions to emergency department and to hospital were prospectively recorded. Differences were studied according to these clinical and demographic variables: age, tumour stage, performance status, weight, height, body mass index, surgery type, chemotherapy type, number of courses, comorbidity, marital status, educational level, social status and occupational status. Results Among 268 patients, 124 (42.2%) required one or more non-protocol health-care encounters. 180 visits were generated (GP 23.3%, specialist 35.5%, emergency department admission 21.1%, hospital admission 8.3%, others 3.3% and more than one resource 8.3%). Of total consultations 150 (83.3%) were chemotherapy-related. The number of visits was higher in the first courses. Fever and infection were the most frequent reasons for consultation in all resources. The dependent variable: ‘need for non-protocol health-care encounter in any course' was statistically associated with age ( p =0.002) and marital status ( p =0.021); no association was found with other variables. In multivariate analysis, age ( p =0.001) and marital status ( p =0.009) remained statistically significant. Younger and married patients consumed less extra health resources. Concluding statement Many patients receiving chemotherapy consume health-care resources in addition to their routine visits, usually treatment-related. Patients consult less in the later courses. Older and unmarried women in particular need extra care during chemotherapy.

Little data is available concerning variations in the clinical characteristics of lymphoid neoplasms at presentation. We decided to investigate whether any variations in these characteristics had occurred in Spain during the last few years.The GOTEL group database is an archive of all new lymphoma cases, regardless of their histological subtype, diagnosed in the hospitals within the group. An analysis was made of all the records between 1 January 1999 and 1 January 2009. Though the number of hospitals submitting data has changed over the course of time, data were provided by 26 hospitals from 16 Spanish provinces.A total of 3651 cases of lymphoma were recorded during this period. Grouped by clinical features, 42.8% (1561 patients) had low-grade lymphoma, 30.4% (1110 patients) intermediate-grade lymphoma and 15.2% (556 patients) Hodgkin's lymphoma; 208 patients had T lymphoma (5.7%), 111 patients high-grade lymphoma (3%) and 105 patients (2.9%) suffered lymphomas that were difficult to classify. A total of 6.3% of the diagnoses (231 patients) were made prior to 1999, 29.5% between 2000 and 2001, 25.7% between 2002 and 2003, 19.7% between 2004 and 2005, 11.2% between 2006 and 2007, and there were 200 entries from 2008 to the close of the study period, corresponding to 1.5% of the complete database. The median age at diagnosis was 60 (range 7-105 years), by percentiles: 25 corresponded to 44 years old, 50 to 60 years old and 75 to 71. Distribution by gender was 53.1% male and 46.9% female. An analysis was made of all the clinical variables collected, comparing their behaviour during the different diagnostic periods. The periods, gender, ECOG, stage, LDH, ß2 microglobulin, Hodgkin's or non- Hodgkin's type neoplasm, B lymphoma vs. Hodgkin's, NK or T, nodal or extra-nodal origin, median age at diagnosis and histological type by region of origin did not show any statistically significant differences in their distribution over the course of time.In our experience, there are no significant variations in clinical presentation or histological type in lymphomas diagnosed over the course of time in Spain.

Objectives: Immediate post-mastectomy breast reconstruction (IBR) is a procedure that has proven advantages, but it also entails risks. The aim of this study was to identify risk factors for reconstruction failure.Methods: A review was made of all the IBR carried out at a general hospital from 2002 to 2009. Retrospective information was obtained about postoperative complications and the characteristics of patients and treatments applied. The minimum follow-up period was 9 months. Cox's regression analysis was performed on the variables related to the reconstruction failure requiring the removal of the prosthesis, with an explanatory model in which all the study variables were introduced and a predictive model that contained only the variables known before the intervention.Results: A total of 115 IRB interventions carried out on 112 women with breast cancer were analyzed. The mean follow-up period was 25.5 months. In sixty cases (52.2 percent), there were no complications; in sixteen cases (13.9 percent) minor complications appeared, and in 39 (33.9 percent) the complications were moderate. In twenty-six cases (22.6 percent), a reconstruction failure occurred. Cox's regression model revealed that the reconstruction failures were related to the patient's age (Hazard Ratio 1.08), to neoadjuvant chemotherapy (HR 6.24) and to postoperative tamoxifen (HR 3.10). The predictive model included the age of the patient (HR 1.05) and the use of neoadjuvant chemotherapy (HR 5.11).Conclusions: A significant proportion of the patients receiving IBR developed reconstruction failure. Multivariate analysis identified three variables related to this complication, two of which were known before the intervention.

Hodgkin's lymphoma is a malignant disease with an incidence of 2.2 cases/100,000. The main goals of staging are to measure the extent of disease and associated prognostic factors. Distinct recommendations were produced for initial work-up, first-line therapy of early and advanced stage disease and treatment of relapsed or resistant patients.

Diffuse large B-cell non-Hodgkin's lymphoma (LDCGB) is one of the best examples of chemotherapy curable malignant diseases. This "Oncoguía SEOM" summarizes the basic directions of staging and recommended treatment options. The staging study should be thorough and includes clinical, laboratory, diagnostic imaging and nuclear medicine. Treatment depends on patient characteristics and comorbidity and on disease extension and prognostic factors. In localized cases, chemoimmunotherapy (CHOP-R) of short duration, followed by involved-field irradiation is the preferred option. In advanced stages, the association of CHOP-like chemotherapy and Rituximab has been a major breakthrough in terms of cure rate. It is important do not forget the supportive treatment in these patients.