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Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I–III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available. [ABSTRACT FROM AUTHOR]

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 <.0001), antibiotics (7 vs. 15 months, P <.017), anxiolytic drugs (8 vs. 16 months, P <.015), and corticosteroids (6 vs. 19 months, P <.00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07–3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77–9.92; P <.001). 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. [ABSTRACT FROM AUTHOR]

The use of immune checkpoint inhibitors has emerged as an effective treatment option for patients with several tumor types. By increasing the activity of the immune system, they can induce inflammatory side effects, which are often termed immune-related adverse events. These are pathophysiologically unique toxicities, compared with those from other anticancer therapies. In addition, the spectrum of the target organs is very broad. Immune-inflammatory adverse events can be life threatening. Prompt diagnosis and pharmacological intervention are instrumental to avoid progression to severe manifestations. Consequently, clinicians require new skills to successfully diagnose and manage these events. These SEOM guidelines have been developed with the consensus of ten medical oncologists. Relevant studies published in peer-review journals were used for the guideline elaboration. The Infectious Diseases Society of America grading system was used to assign levels of evidence and grades of recommendation. [ABSTRACT FROM AUTHOR]

Immunology and immunotherapy of cancer is an expanding field in oncology, with recent great achievements obtained through the new successful approaches implemented to circumvent immune evasion, which is undoubtedly considered a novel hallmark of cancer. Translational research in this topic has revealed targets that can be modulated in the clinical setting with new compounds and strategies. Like most of the tumors, breast cancer is considered a complex and heterogeneous disease in which host immune responses have been also recently demonstrated of critical relevance. T infiltrating lymphocyte measurement is suggested as a powerful new tool necessary to predict early breast cancer evolution, especially for the her2-positive and triple-negative subtypes. Other biomarkers in tissue and peripheral blood are under intense scrutiny to ascertain their eventual role as prognostic and/or predictive factors. This background has fueled the interest in developing clinical research strategies to test activity of modern immunotherapy in breast cancer, which constitutes the main focus of this review. [ABSTRACT FROM AUTHOR]

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference. [ABSTRACT FROM AUTHOR]

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed. [ABSTRACT FROM AUTHOR]

Surveillance is an interesting application for Unmanned Aerial Vehicles (UAVs). If a team of UAVs is considered, the objective is usually to act cooperatively to gather as much information as possible from a set of moving targets in the surveillance area. This is a decision-making problem with severe uncertainties involved: relying on imperfect sensors and models, UAVs need to select targets to monitor and determine the best actions to track them. Partially Observable Markov Decision Processes (POMDPs) are quite adequate for optimal decision-making under uncertainties, but they lack scalability in multi-UAV scenarios, becoming tractable only for toy problems. In this paper, we take a step forward to apply POMDP methods in real situations, where the team needs to adapt to the circumstances during the mission and foster cooperation among the team-members. We propose to split the original problem into simpler behaviors that can be modeled by scalable POMDPs. Then, those behaviors are auctioned during the mission among the UAVs, which follow different policies depending on the behavior assigned. We evaluate the performance of our approach with extensive simulations and propose an implementation with real quadcopters in a testbed scenario. [ABSTRACT FROM AUTHOR]

Objectives: Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF mutated advanced melanoma. We investigated safety, tolerability and efficacy of vemurafenib in Spanish patients participating in that study. Methods: Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAF mutation-positive melanoma received vemurafenib 960 mg twice daily until disease progression, unacceptable toxicity, withdrawal of consent or death. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: 301 Spanish patients were included, 70 % with M1c disease, 22 % with brain metastases and 51 % with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48 %), arthralgia (45 %), rash (41 %), photosensitivity (34 %) and skin neoplasms (21 %). Grade 3/4 adverse events occurred in 156 patients (52 %), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16 %), fatigue (6 %) and arthralgia (5 %). The ORR was 28 % (95 % CI 23-34 %). Responses occurred in patients with brain metastases (18 %), elevated baseline lactate dehydrogenase (19 %) and poor performance status (15 %), and elderly patients (22 %). Median PFS was 5.8 (95 % CI 5.0-6.4) months; median OS was 10.5 (95 % CI 9.5-13.5) months. Conclusion: Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment. [ABSTRACT FROM AUTHOR]

Introduction: Ipilimumab has been approved in patients with advanced melanoma by different regulatory bodies worldwide, but its use in clinical practice is not fully consistent among oncologists. We have surveyed a representative sample of Spanish medical oncologists on issues related to the use of ipilimumab. Materials and methods: The survey was based on the Delphi method, where experts respond anonymously to two rounds of a questionnaire. Questionnaire consisted of 42 statements divided among the following eight categories: Pathology and Diagnosis; Patterns of Response; Parameters affecting Treatment Selection; Patient Profile; Sequencing of Treatment; Definition of Long-Term Survivors; Quality of Life; Concept of Immuno-oncology. The experts were asked to rate each statement on a scale of 1-9, where 1 meant 'completely disagree' and 9 meant 'completely agree'. Results: Thirty-three oncologists responded to both rounds of the survey (62.3 % of total surveyed). On issues related to pathology and diagnosis, patterns of response, and immuno-oncology, the specialists reached a high level of consensus. There was also a high level of agreement, albeit without consensus on assessment of BRAF mutations before deciding on treatment with ipilimumab. However, there was a lower level of agreement on sequencing treatment with BRAF inhibitors and ipilimumab, on predictive factors, on the use of corticosteroids, and on patient quality of life. Conclusions: The disparity in many of these topics suggests that oncologists need more information on certain aspects of ipilimumab treatment. We need to define generally accepted algorithms of treatment, especially with regard to issues that were shown to be controversial or unclear. [ABSTRACT FROM AUTHOR]

Introduction: The development of novel mechanical endoscopic closure systems allows now the management of some gastrointestinal fistula types in a minimally invasive way. However, the correct location of the fistulous tract is essential to achieve successful endoscopic closure.Case report: A 69-year-old woman with high risk for surgery presented with recurrent cystitis, pneumaturia, and enteruria 2 months after medical-treated diverticulitis. Computerized tomography demonstrated colovesical fistula but colonoscopy could not locate the fistulous opening. A cystoscopy was performed and the fistulous tract was shown using a guidewire. Then, a novel over-the-scope clip device Padlock® system was released in the sigmoid colon, with successful endoscopic closure through this not previously described collaborative approach between urologists, surgeons, and gastroenterologists. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is an uncommon B cell lymphoid malignancy representing approximately 10-15 % of all lymphomas. HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte-predominant HL. An accurate assessment of the stage of disease and prognostic factors that identify patients at low or high risk for recurrence are used to optimize therapy. Patients with early stage disease are treated with combined modality strategies using abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. Brentuximab vedotin should be considered for patients who fail HDCT with ASCT. [ABSTRACT FROM AUTHOR]

Follicular non-Hodgkin's lymphoma (FL) is a nodal B lymphoid malignancy that originates from the germinal center of a lymph node. FL is the second most frequent lymphoma subtype. The course of the disease is usually characterised by a typically indolent clinical course, with a median survival rate of 8-10 years, although most patients relapse after treatment. Diagnosis should always be based on a surgical specimen like an excisional node lymph biopsy. The first-line treatment of FL will depend of extension disease, tumour burden, patient symptoms, performance status and also patient decision. The addition of rituximab to conventional chemotherapy has improved ORR, PFS and OS. As first line in patients that need treatment, a combination of chemotherapy with rituximab induction followed by 2 years of rituximab maintenance is the best option. High-dose chemotherapy with autologous stem-cell transplantation in first line has not shown improvement and is not recommended as first-line therapy. Before any treatment decision in relapsed patients, a repeat biopsy is mandatory to rule out a transformation into large cell aggressive lymphoma. Standard treatment is controversial, depends on the efficacy of prior treatment, duration of the time-to-relapse, patient's age and histological findings at relapse. [ABSTRACT FROM AUTHOR]

Metastatic breast cancer is essentially an incurable disease. However, recent advances have resulted in a significant improvement of overall survival. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with metastatic breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference. [ABSTRACT FROM AUTHOR]

Purpose: Trastuzumab has proven to improve the prognosis of HER2-positive breast cancer, but the information available about its administration for small tumors is still limited. Therefore, we assessed the use of adjuvant regimens with trastuzumab for the treatment of small HER2-positive breast cancer in routine clinical practice. Methods: This observational study was conducted in patients with HER2-positive breast adenocarcinoma ≤1.5 cm who received trastuzumab-based adjuvant treatment in clinical practice. Clinical/histopathological data were retrieved from patients' medical charts. Results: A total of 101 evaluable patients were enrolled (median age [range], 56.7 [49.0-64.8] years; ECOG 0, 98.0 %; ductal carcinoma, 88.1 %; lymph nodes N0, 79.2 %). Only five (5.0 %) patients received neoadjuvant treatment, while all patients underwent tumor surgery. Adjuvant trastuzumab was administered at a mean (±SD) dose of 5.9 ± 1.5 mg/kg/cycle, and mostly in a three-weekly schedule (89 [89.0 %] patients). The most frequent adjuvant therapy used with trastuzumab was chemotherapy (87 [86.1 %] patients), followed by radiotherapy (63 [62.4 %] patients) and hormone therapy (52 [51.5 %] patients). Chemotherapy regimens mainly included doxorubicin, cyclophosphamide and paclitaxel/docetaxel ( n = 30), docetaxel and cyclophosphamide ( n = 15), docetaxel and carboplatin ( n = 13). Hormone therapy mainly included letrozole ( n = 17) and tamoxifen ( n = 17). Nine (8.9 %) patients reported trastuzumab-related adverse events; only one allergic reaction reached grade 3 toxicity. Conclusion: This study shows that trastuzumab-based adjuvant treatment of small HER2-positive breast cancer is mostly based on chemotherapy-mainly paclitaxel/docetaxel. Adjuvant administration of trastuzumab for small HER2-positive breast cancer seems to be similar to that used for larger tumors. [ABSTRACT FROM AUTHOR]

We present the physical parameters of the regions with spectral line formation of a set of stars classified as G2. The method employed in this analysis only requires the full width at half maximum of each spectral line, the effective temperature of the star, and few basic atomic parameters. The physical parameters estimated in this work are compared with results obtained with stellar atmosphere models. [ABSTRACT FROM AUTHOR]

Cancer of unknown primary site is a histologically confirmed cancer which is manifested in advanced stage, with no identifiable primary site after the use of standard diagnostic procedures. Patients are initially placed into one of categories based upon the examination of the initial biopsy: adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma and poorly differentiated carcinoma. Appropriate patient management requires an understanding of several clinicopathologic features that help to identify several subsets of patients with more responsive tumors. [ABSTRACT FROM AUTHOR]

Introduction: This is a retrospective case report of three cases with an early postoperative transtibial fistula after anterior cruciate ligament reconstruction (ACL). Materials and methods: The patients had undergone ACL reconstruction and complained of fluid drainage through the not-healed wound or swelling localized on the anteromedial aspect of the ipsilateral proximal tibia during the early postoperative. Magnetic resonance imaging showed a multilocular fluid-filled cyst arising from the distal hole of the tibial bone tunnel. Open resection of the fistula and the cyst was performed in all cases and communication between the tibial tunnel and the joint space was confirmed. During revision surgery the distal hole of the tibial tunnel was covered with a fascio-periosteal flap. Results: All wounds healed without complications. There was no recurrence of drainage or cyst formation. At 2 years follow-up the knee function was normal and was not affected by the complication in any of the patients. Early postoperative transtibial fistulae after ACL reconstruction are rare complications that clinically present either as anterior tibial cysts or persistent wound drainage. Surgical treatment is required, and some delay in the rehabilitation routine is required, but the final outcome is not affected. [ABSTRACT FROM AUTHOR]

We present a procedure to make direct diagnostics of the physical conditions of the regions of formation of the atomic spectral lines in stellar atmospheres using the atomic line widths at half maximum and the number of lines visible of a given atomic series in the observed stellar spectra. This is accomplished using the theoretical widths at half maximum of the atomic lines induced by the broadening produced by thermal energy fluctuations and considering the maximum number of levels that exist in those atoms under the physical conditions of the given system. The procedure is easy to use in any application. As an example we apply the procedure to the observed Lyman lines of hydrogen in the ultraviolet of some stars. [ABSTRACT FROM AUTHOR]

The extracellular protease production capacity of 840 bacterial strains isolated during the austral summers of 1989/90 and 1991/92 from different sources of the Antarctic ecosystem was analysed in skim-milk agar plates. Thirty-four psychrotrophic strains were selected, classified at genus level and tested from proteolytic activity by the azocasein method from the cell-free supernatant of submerged cultures. Thirty-two of the selected strains were Gram-negative bacteria and Pseudomonas was the predominant genus. Three Pseudomonas maltophilia strains showed the highest levels of proteolytic activity at 20°C. No correlation was observed between the proteolytic activity estimated by the ring of hydrolysis in skim-milk agar plates and the activity measured by the azocasein method. The results suggest that these psychrotrophic strains are potentially useful for developing a biotechnological process to produce proteases with high activity at moderate temperatures. [ABSTRACT FROM AUTHOR]

In Sweden import of irradiated food is not permitted (spices excepted, 1997). In this regard the Swedish National Food Administration (NFA) has adopted two analytical methods for controlling imported irradiated food: the DNA comet assay for screening and the hydrocarbon method as a confirmatory method. We report here the results of analyses of various samples imported to Sweden from different countries during the last 7 years. It was demonstrated that the control of irradiated food could be reliably performed using these methods. [ABSTRACT FROM AUTHOR]