Alcohol, health and cardiovascular disease. / Alcohol, salud y enfermedad cardiovascular.

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive.

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up.

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

BACKGROUND: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. PATIENTS AND METHODS: Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. RESULTS: Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). CONCLUSIONS: The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.

Personalizing, not patronizing: the case for patient autonomy by unbiased presentation of management options in stage I testicular cancer.

Testicular cancer (TC) is the most common neoplasm in males aged 15-40 years. The majority of patients have no evidence of metastases at diagnosis and thus have clinical stage I (CSI) disease [Oldenburg J, Fossa SD, Nuver J et al. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24(Suppl 6): vi125-vi132; de Wit R, Fizazi K. Controversies in the management of clinical stage I testis cancer. J Clin Oncol 2006; 24: 5482-5492.]. Management of CSI TC is controversial and options include surveillance and active treatment. Different forms of adjuvant therapy exist, including either one or two cycles of carboplatin chemotherapy or radiotherapy for seminoma and either one or two cycles of cisplatin-based chemotherapy or retroperitoneal lymph node dissection for non-seminoma. Long-term disease-specific survival is ∼99% with any of these approaches, including surveillance. While surveillance allows most patients to avoid additional treatment, adjuvant therapy markedly lowers the relapse rate. Weighing the net benefits of surveillance against those of adjuvant treatment depends on prioritizing competing aims such as avoiding unnecessary treatment, avoiding more burdensome treatment with salvage chemotherapy and minimizing the anxiety, stress and life disruption associated with relapse. Unbiased information about the advantages and disadvantages of surveillance and adjuvant treatment is a prerequisite for informed consent by the patient. In a clinical scenario like CSI TC, where different disease-management options produce indistinguishable long-term survival rates, patient values, priorities and preferences should be taken into account. In this review, we provide an overview about risk factors for relapse, potential benefits and harms of adjuvant chemotherapy and active surveillance and a rationale for involving patients in individualized decision making about their treatment rather than adopting a uniform recommendation for all.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

2-¹8fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) for postchemotherapy seminoma residual lesions: a retrospective validation of the SEMPET trial.

BACKGROUND: 2-¹8fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) has been recommended in international guidelines in the evaluation of postchemotherapy seminoma residuals. Our trial was designed to validate these recommendations in a larger group of patients. PATIENTS AND METHODS: FDG-PET studies in patients with metastatic seminoma and residual masses after platinum-containing chemotherapy were correlated with either the histology of the resected lesion(s) or the clinical outcome. RESULTS: One hundred and seventy seven FDG-PET results were contributed. Of 127 eligible PET studies, 69% were true negative, 11% true positive, 6% false negative, and 15% false positive. We compared PET scans carried out before and after a cut-off level of 6 weeks after the end of the last chemotherapy cycle. PET sensitivity, specificity, negative predictive value (NPV), and positive predictive value were 50%, 77%, 91%, and 25%, respectively, before the cut-off and 82%, 90%, 95%, and 69% after the cut-off. PET accuracy significantly improved from 73% before to 88% after the cut-off (P=0.032). CONCLUSION: Our study confirms the high specificity, sensitivity, and NPV of FDG-PET for evaluating postchemotherapy seminoma residuals. When carried out at an adequate time point, FDG-PET remains a valuable tool for clinical decision-making in this clinical setting and spares patients unnecessary therapy.

Brief report: phase II multicenter study of temozolomide in patients with cisplatin-resistant germ cell tumors.

PURPOSE: To determine the activity and toxicity of temozolomide in a phase II multicenter trial in patients diagnosed with relapsed or cisplatin-refractory germ cell tumors. PATIENTS AND METHODS: During a recruitment period of 30 months, 20 patients received temozolomide 150 mg/m(2)/day p.o. for 5 days every 4 weeks, escalating to 200 mg/m(2)/day if grade II toxicity was not observed in the first cycle. Eligibility criteria were tumor progression or relapse after previous cisplatin and ifosfamide-containing chemotherapy, creatinine clearance of >40 ml/min, and a performance status of 0-2. RESULTS: The median age was 38 years (range 27-56). Seventeen patients had nonseminomatous tumors, and 3 had seminomatous tumors. Six of the patients had extragonadal primary tumors (3 retroperitoneal and 3 mediastinal). The median number of prior cisplatin-containing cycles was 11 (range 7-20). Eight patients received prior high-dose chemotherapy and 14 were refractory or absolutely refractory to cisplatin. A total of 45 cycles were administered. Two partial responses lasting 9 and 3.5 months (overall response rate 10%, 95% CI 1.2-31.7) were observed. One of these responses was seen in a patient with a cisplatin-refractory tumor that had previously been treated with high-dose chemotherapy. The median time to progression and the median overall survival were 1.5 and 3.1 months, respectively. Grade III hematological toxicity consisted of thrombocytopenia in 2 patients and anemia in 1 patient. No grade IV toxicity was observed. CONCLUSIONS: Temozolomide had some activity in heavily pretreated patients resistant to cisplatin-based chemotherapy.

Alcohol, health and cardiovascular disease.

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100 g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive.

SEOM clinical guidelines for the management of germ cell testicular cancer (2016).

Testicular cancer represents the most common malignancy in males aged 15-34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3-4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

[Lymphomas originating in the otorhinolaryngeal region: 10 years' experience]. / Linfomas originados en el área otorrinolaringológica: experiencia de 10 años.

BACKGROUND: Non-Hodgkin's lymphomas (NHL) originated in the otorhinolaryngological (ORL) area are rare diseases and its therapy is poorly established. METHODS: The diagnostic features, treatment and outcome based on therapy of 34 NHLs originated in the ORL area and seen in the Oncology Service from the Hospital de la Santa Creu i Sant Pau during a ten year period were reviewed. RESULTS: The predominant primary localization was the tonsil (17 patients), followed by rhinopharynx (8), massive involvement of Waldeyer's ring (4), and oropharynx, maxillary sinus and larynx in the remaining cases. In 26 patients the diagnosis was high-grade lymphoma. The stage distribution was 8 patients (24%) in stage I, 16 in stage II (47%), 3 in stage III (9%), and 5 in stage IV (16%). The treatment was heterogeneous and consisted in chemotherapy in 29 patients (38%), radiotherapy in 5 (15%) or the combination of both in 16 (47%). Eleven patients relapsed (38%), more commonly those treated with radiotherapy. The specific actuarial survival was 69%. CONCLUSIONS: NHL originated in the ORL area are uncommon neoplastic diseases, with a commonly dramatic response to chemotherapy. This should be the initial therapeutic modality in all cases.

[The modification of the toxicity produced by chemotherapy in testicular cancer by adapting its intensity to prognostic groups]. / Modificación de la toxicidad producida por la quimioterapia en el cáncer de testículo al adecuar su intensidad a los grupos pronósticos.

BACKGROUND: The reduction of iatrogenesis is fundamental in the treatment of germ-cell testicular tumors (GTT) because of the high incidence of cures achieved. On the other hand, the tumoral mass and the serum concentration of the beta fraction of the gonadotropin hormone (CGH) and of alphafetoprotein allow the differentiation of 2 clear prognostic groups; those for which the intensity of chemotherapy may be adapted to reduce its collateral effects and improve the results. METHODS: In the Oncology Department of the Hospital de la Santa Creu i Sant Pau 23 patients with GTT of good prognosis were treated between 1984-1990. These patients were given the combination of etoposide-cisplatin (EP) over the same period. Twenty patients with a bad prognosis received the alternative scheme of bleomycin-vincristine-methotrexate-cisplatin/etoposide-cisplatin- phosphamide (BOMP/EPI). RESULTS: In comparison to the classical treatment with cisplatin-vinblastine-bleomycin (PVB) the EP association demonstrated less iatrogenesis except in regards to the formation of granulocytopenia which was higher. The BOM/EPI combination conditioned greater hematological toxicity during the acute phase and the first observations suggested a diminution of chronic iatrogenesis. CONCLUSIONS: These results indicate that chemotherapy in testicular cancer may be adapted to the aggressiveness of the with the aim to thereby reduce global toxicity.

[Does total androgen suppression in advanced prostatic cancer induce a greater number of complete remissions? A phase II trial]. / Induce la supresión androgénica total en cáncer de próstata avanzado mayor no. de remisiones completas? Un ensayo en fase II.

The present Phase II study's main objective was to evaluate the rate of complete responses (CR) obtained through total androgenic suppression (TAS) in patients with disseminated prostate carcinoma. Twenty consecutive patients were recruited of which 19 were evaluable for response and toxicity. Treatment consisted in an association of orchiectomy or the analogous LH-RH Buselerin with the antiandrogenic Flutamide. There was 1 CR (5%) and 17 partial responses (PR). Sixteen patients with symptomatic disease had subjective improvement, usually during the first month of treatment. After an average follow-up of 20 months (range 7-29), 1 patient remains CR and 7 have regressed following PR, 4 of which have died. Tolerance was good, and side effects secondary to hypoandrogenism were frequent, although mild, requiring treatment discontinuation in 1 case. It is concluded that TAS is an excellent palliative approach in disseminated prostate carcinoma though the rate of CRs obtained is sensibly lower to that reported by Labrie (28.3%) and in the range of 0-8% achieved in most studies. It is questionable whether it will become standard therapy for metastatic prostate carcinoma.

Synchronous versus metachronous brain metastasis from testicular germ cell tumors (TGCT): an analysis from the Spanish Germ Cell Cancer Group data base.

BACKGROUND: Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. PATIENTS AND METHODS: A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. RESULTS: Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). CONCLUSION: Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution.

Alcohol, salud y enfermedad cardiovascular / Alcohol, health and cardiovascular disease

Estudios epidemiológicos recientes han demostrado que el consumo de alcohol puede aumentar el riesgo de hipertensión arterial, fibrilación auricular y de cáncer digestivo y de mama, por lo que diversos estamentos están promoviendo la abstinencia. Sin embargo, también han vuelto a confirmar que el consumo ligero de alcohol puede reducir el riesgo de infarto de miocardio y de diabetes, no quedando claro el efecto en la enfermedad cerebrovascular. Por ello, la decisión del consumo de alcohol debe ser individual y basada en factores personales. Un nivel de consumo<100g/semana en hombres (menor en mujeres), parece que no aumenta la mortalidad por cualquier causa, mientras que consumos elevados o en forma de atracón (binge) incrementan significativamente el riesgo de mortalidad, por lo cual deben aplicarse todas las medidas para prevenir este tipo de consumo, especialmente en la población más joven. Hay datos que apuntan una ventaja del vino frente a las otras bebidas, pero no son concluyentes (AU)

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption <100g/week for men (less for women) appears not to increase all-cause mortality, while high consumption or binge drinking significantly increases mortality risk. All measures to prevent this type of consumption, especially among the younger population, should therefore be applied. There are data indicating an advantage of wine over other beverages, but they are not conclusive (AU)