Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry.

BACKGROUND: Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. MATERIALS AND METHODS: Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. RESULTS: Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. CONCLUSIONS: This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.

No priming, just fighting-endophytic yeast attenuates the defense response and the stress induced by Dutch elm disease in Ulmus minor Mill.

One century after the first report of Dutch elm disease (DED), there is still no practical solution for this problem threatening European and American elms (Ulmus spp.). The long breeding cycles needed to select resistant genotypes and the lack of efficient treatments keep disease incidence at high levels. In this work, the expression of defense-related genes to the causal agent of DED, Ophiostoma novo-ulmi Brasier, was analyzed in in vitro clonal plantlets from two DED-resistant and two DED-susceptible Ulmus minor Mill. trees. In addition, the effect of the inoculation of an endophytic pink-pigmented yeast (Cystobasidium sp.) on the plant's defense system was tested both individually and in combination with O. novo-ulmi. The multifactorial nature of the resistance to DED was confirmed, as no common molecular response was found in the two resistant genotypes. However, the in vitro experimental system allowed discrimination of the susceptible from the resistant genotypes, showing higher levels of oxidative damage and phenolic compounds in the susceptible genotypes after pathogen inoculation. Inoculation of the endophyte before O. novo-ulmi attenuated the plant molecular response induced by the pathogen and moderated oxidative stress levels. Niche competition, endophyte-pathogen antagonism and molecular crosstalk between the host and the endophyte are discussed as possible mechanisms of stress reduction. In sum, our results confirm the complex and heterogeneous nature of DED resistance mechanisms and highlight the possibility of using certain endophytic yeasts as biological tools to improve tree resilience against biotic stress.

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia.

BACKGROUND: There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. CASE PRESENTATION: Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. CONCLUSIONS: Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

Perirenal Fat Surface Area and Oncologic Outcome in Elective Colon Cancer Surgery.

BACKGROUND: Central obesity is associated with surgical difficulties, but few studies explore the relationship with long-term results after colon cancer surgery. OBJECTIVE: The purpose of this study was to investigate the association between perirenal fat surface area, a proxy for total visceral fat, and oncologic outcome after intestinal resection for colon cancer. DESIGN: We investigated the association between perirenal fat surface area (exposure) on recurrence and death (outcome) in patients undergoing surgery with curative intent for colon cancer. SETTINGS: The study was conducted at Stockholm South General Hospital, serving a population of 600,000. PATIENTS: Patients (N = 733) without metastases at diagnosis who had a preoperative CT and had undergone elective colon resection between 2006 and 2016 were included. MAIN OUTCOME MEASURES: We compared overall survival, recurrence-free survival, and cause-specific survival by perirenal fat surface area. RESULTS: Patients with high perirenal fat surface area (fourth quartile) had more often left-sided tumors (45% vs 32% in the first quartile) and experienced more postoperative complications (29% vs 13%), but there were no differences in pathologic T and N stage, radicality of surgery, or adjuvant chemotherapy treatment. Overall survival decreased by increasing cancer stage but was not different between perirenal fat surface area categories. The HR for recurrence-free survival per centimeter squared increase in perirenal fat surface area was 1.00 (95% CI, 0.99-1.01) adjusted for age, sex, ASA category, tumor location, and postoperative complication Clavien-Dindo ≥2. The cumulative incidence of recurrence with death as a competing risk was not statistically different between perirenal fat surface area categories (p = 0.06). Subgroup analyses showed a nonsignificant tendency for men with low perirenal fat surface area to have a lower risk of recurrence and women a higher risk. LIMITATIONS: In all register-based studies there can be randomly distributed errors. The results can only be generalized to colon resections. Our cohort ranged over a large year span. CONCLUSIONS: We found no association between perirenal fat surface area and overall survival, recurrence-free survival, or cause-specific cumulative incidence of recurrence in patients undergoing colon resection for cancer. See Video Abstract at http://links.lww.com/DCR/B326. LA SUPERFICIE DE GRASA PERIRRENAL Y EL RESULTADO ONCOLGICO EN CIRUGA ELECTIVA DE CNCER DE COLON: ANTECEDENTES:La obesidad central está asociada con dificultades quirúrgicas, pero pocos estudios exploran la relación de los resultados a largo plazo después de cirugía de cáncer de colon.OBJETIVO:Investigar la asociación entre la superficie de la grasa perirrenal, como un indicador de la grasa visceral total y el resultado oncológico después de una resección intestinal por cáncer de colon.DISEÑO:Se estudió la asociación entre el área de la superficie de la grasa perirrenal (expuesta) con la recurrencia y la muerte (resultado) de pacientes sometidos a cirugía con intención curativa por cáncer de colon.AJUSTES:Atención brindada por el Hospital General del Sur de Estocolmo a una población de 600,000 habitantes.PACIENTES:Aquellos pacientes sin metástasis (n = 733) en el momento del diagnóstico que tuvieron una tomografía computada preoperatoria y que se sometieron a una resección electiva de colon entre 2006-2016.PRINCIPALES MEDIDAS DE RESULTADO:Comparamos la sobrevida general, la sobrevida libre de recurrencia y la sobrevida específica de la causa, por área de superficie de grasa perirrenal.RESULTADOS:Los pacientes con una mayor área de superficie de grasa perirrenal (cuarto cuartil) tuvieron más frecuentemente tumores del lado izquierdo (45% frente a 32% en el primer cuartil) y sufrieron más complicaciones postoperatorias (29% frente a 13%), pero no hubieron diferencias en el Estadío patológico T y N, ni en lo radical de la cirugía o del tratamiento de quimioterapia adyuvante. La supervivencia general disminuyó al aumentar el estadio del cáncer, pero no fue diferente entre las categorías de área de superficie grasa perirrenal. La razón de riesgo para la sobrevida libre de recurrencia por aumento de cm2 en el área de la superficie grasa perirrenal fue de 1.00 (intervalo de confianza del 95%: 0.99-1.01) ajustada por edad, sexo, categoría de la Sociedad Americana de Anestesiólogos, ubicación del tumor y complicación postoperatoria según Clavien-Dindo ≥ 2) La incidencia acumulada de recurrencia con muerte como un riesgo competitivo no fue estadísticamente diferente entre las categorías de área de superficie grasa perirrenal (p = 0.06). Los análisis de subgrupos mostraron una tendencia no significativa para que los hombres con un área de superficie menor en grasa perirrenal tengan un menor riesgo de recurrencia y las mujeres un mayor riesgo.LIMITACIONES:En todos los estudios basados en registros puede haber errores distribuidos aleatoriamente. Los resultados solo pueden generalizarse a resecciones de colon. Nuestra cohorte osciló durante un gran lapso de años.CONCLUSIONES:No se encontró asociación entre el área de superficie de la grasa perirrenal y la sobrevida general, ni con la sobrevida libre de recurrencia o la incidencia acumulada de recurrencia específica de la causa en pacientes sometidos a resección de colon por cáncer. Consulte Video Resumen en http://links.lww.com/DCR/B326. (Traducción-Dr Xavier Delgadillo).

SEOM clinical guideline for the management of immune-related adverse events in patients treated with immune checkpoint inhibitors (2019).

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.

Associação à positividade da Lawsonia intracellularis com a expressão clínico-patológica da infecção em suínos da região metropolitana de Bucaramanga (Santander, Colômbia) / Association to positivity of Lawsonia intracellularis with the clinical and pathologic expression of infection in swine from the metropolitan area of Bucaramanga (Santander, Colombia)

Porções de íleo terminal foram coletados de 100 suínos com sinais de doença gastrointestinal na área metropolitana de Bucaramanga, a fim de se estudar a eficiência do diagnóstico de enteropatia proliferativa suína (PPE) pela técnica de PCR aninha (PCRa) empregando sequências específicas (primers) para L. intracellularis: 16S ARN região (270pb) e sua correlação com achados clínicos e patológicos. Todas as amostras foram processadas para se determinar a associação entre positividade por PCR, os sinais clínicos, os achados de necropsia e as lesões histológicas. Cinquenta e seis por cento das amostras foram positivas para L. intracellularis pela PCRa. Só 2% exibiram resultados positivos pela técnica Warthin-Starry. Trinta e um de 100 animais com sinais de anorexia resultaram positivos para PCRa (P>0,05). Não houve associação (P<0,05) entre diarreia e queda no crescimento, bem como associação (P<0,05) entre achados anatomopatológicos e histológicos com PCRa positivas.(AU)

Fragments of terminal ileum were collected from 100 pigs at slaughter from Bucaramanga Metropolitan Area (Santander, Colombia), to study the efficacy of the diagnosis of porcine proliferative enterophaty (PPE) through the technique of nested polymerase chain reaction (PCRa), employing specific sequences (primers) for L. intracellularis: 16S ARN region (270pb) and his correlation with clinic and pathological findings. All samples were processed by standard histological methods and stained with a Warthin-Starry technique. All samples were processed to determinate the association between positive PCRa results, clinical signs and necropsy findings. 56% of the 100 samples were positive for L. intracellularis through PCRa technic. Only 2% exhibited positive results through Warthin-Starry technique. A total of 31 (100) animals with anorexic symptoms were associated with positive results from PCRa (P>,05). No associations (P<0.05) were observed between diarrhea and delayed growth. No associations (P<0.05) were observed between anatomopathological and histological findings with positive PCRa.(AU)

Trends in the Management of Acute Appendicitis in a Single-Center Quality Register Cohort of 5,614 Patients.

Acute appendicitis is one of the most common reasons for emergency surgery. At Stockholm South General Hospital, information on all patients - 15 years or older - undergoing surgery for acute appendicitis is included in a quality register. Data on surgical method, preoperative imaging, hospital stay, intraoperative findings, and 30-day complications were recorded for each patient. From January 2004 to December 2014, 5,614 consecutive patients were registered. The percentage of patients examined with preoperative imaging increased from 30% in 2004 to 93% in 2014. The use of laparoscopic appendectomy increased from 6 to 79%. Negative appendectomies decreased from 7.5-10 to 1.7%. The mean perforation rate was 28.6%. Some form of postoperative complication occurred in 6.6% of those on whom laparoscopy was performed and 10.5% of those who underwent an open surgery, with a significant difference (p < 0.001) in the rate of surgical site infections (surgical site infections, higher in open cases) but with no difference in the number of deep postoperative abscesses. The overall hospital stay decreased from 2004 to 2014 for perforated and non-perforated appendicitis. The overall 30-day mortality rate was 0.12%. Changes in preoperative imaging and treatment strategy for appendicitis during this period resulted in a lower rate of negative appendectomies with acceptable complication rates and shortened hospital stay.

A phase II study of a human anti-PDGFRα monoclonal antibody (olaratumab, IMC-3G3) in previously treated patients with metastatic gastrointestinal stromal tumors.

Background: This study evaluated tumor response to olaratumab (an anti-PDGFRα monoclonal antibody) in previously treated patients with metastatic gastrointestinal stromal tumor (GIST) with or without PDGFRα mutations (cohorts 1 and 2, respectively). Patients and methods: Patients received olaratumab 20 mg/kg intravenously every 14 days until disease progression, death, or intolerable toxicity occurred. Outcome measures were 12-week tumor response, progression-free survival (PFS), overall survival (OS), and safety. Results: Of 30 patients enrolled, 21 patients received ≥1 dose of olaratumab. In the evaluable population (cohort 1, n = 6; cohort 2, n = 14), no complete response (CR) or partial response (PR) was observed. Stable disease (SD) was observed in 3 patients (50.0%) in cohort 1 and 2 patients (14.3%) in cohort 2. Progressive disease (PD) was observed in 3 patients (50.0%) in cohort 1 and 12 patients (85.7%) in cohort 2. The 12-week clinical benefit rate (CR + PR + SD) (90% CI) was 50.0% (15.3-84.7%) in cohort 1 and 14.3% (2.6-38.5%) in cohort 2. SD lasted beyond 12 weeks in 5 patients (cohort 1, n = 3; cohort 2, n = 2). Median PFS (90% CI) was 32.1 (5.0-35.9) weeks in cohort 1 and 6.1 (5.7-6.3) weeks in cohort 2. Median OS was not reached in cohort 1 and was 24.9 (14.4-49.1) weeks in cohort 2. All patients in cohort 1 and 9 (64.3%) in cohort 2 experienced an olaratumab-related adverse event (AE), most commonly fatigue (38.1%), nausea (19.0%), and peripheral edema (14.3%). Two grade ≥3 olaratumab-related events were reported (cohort 1, syncope; cohort 2, hypertension). Conclusions: Olaratumab had an acceptable AE profile in patients with GIST. While there was no apparent effect on PFS in patients without PDGFRα mutations, patients with PDGFRα-mutant GIST (all with D842V mutations) treated with olaratumab had longer disease control compared with historical data for this genotype. ClinicalTrials.gov Identifier: NCT01316263.

Evaluation of the efficacy of therapeutic endoscopy in gastrointestinal bleeding secondary to angiodysplasias. / Evaluación de la eficacia terapéutica endoscópica en hemorragia digestiva secundaria a angiodisplasias.

INTRODUCTION: Gastrointestinal angiodysplasias are defined as vascular dilations that communicate capillaries and veins in the walls of the digestive tract. The clinical presentation of these lesions varies from chronic occult bleeding to severe gastrointestinal hemorrhage. AIM: The primary aim of our study was to analyze lesion location, the efficacy of therapeutic endoscopy with argon plasma coagulation, and the factors associated with rebleeding in patients with gastrointestinal angiodysplasias. MATERIAL AND METHODS: A retrospective study of 32,042 endoscopies was carried out within the time frame of January 2012 and December 2013 at our hospital center. Gastrointestinal angiodysplasia was the diagnosis in 331 of the endoscopies. The procedures included upper gastrointestinal endoscopy, colonoscopy, sigmoidoscopy, and enteroscopy. RESULTS: The most frequent location of the angiodysplasias was the cecum (49%), followed by the ascending colon (17%) and the sigmoid colon (16%). They were most frequently found in the duodenum (60%) and gastric body (49%) at upper gastrointestinal endoscopy. Therapeutic endoscopy was performed in 163 cases (49.8%) and the most predominant methods were fulguration with argon (90%) and combination treatment (argon plasma coagulation and injection sclerotherapy) (6.7%). The macroscopic rebleeding rate after therapeutic endoscopy was 7.4%. Patients that had rebleeding presented with a lower hemoglobin concentration, higher mean age, and the presence of multiple angiodysplasias at endoscopy (P<.05). CONCLUSIONS: Therapeutic endoscopy was performed in 49.8% of the patients with angiodysplasias. The macroscopic rebleeding rate after treatment was 7.4%. There were statistically significant differences in the patients with rebleeding in relation to mean age, hemoglobin values, and the presence of multiple angiodysplasias.

Nontraumatic posterior urethral stenosis. / Patología estenótica no traumática de la uretra posterior.

INTRODUCTION: Posterior urethral stenoses and contractures are complications after treatment of benign prostatic hyperplasia (BPH), localised prostate cancer (PCa), and orthotopic neobladder formation, compromising prognosis and functional outcomes. OBJECTIVES: To identify factors related to aetiology, prevention and treatment of non-traumatic posterior urethral stenosis and contractures. ACQUISITION OF EVIDENCE: Review of the published evidence related to posterior urethral stenosis and contractures after PCa treatment, BPH therapies and orthotopic neobladder formation. PubMed database search with English and Spanish papers considered. Cohort studies, case series, prospective and retrospective studies and review papers were included. SYNTHESIS OF EVIDENCE: Posterior urethral stenoses and contractures are common, leading to significant morbidity. A worsening on voiding quality should rise some concerns. Careful surgical and/or radiotherapic techniques prevent their development. Endoscopic therapies are the initial approach, with complex urethroplasties often required. Subsequent urinary incontinence, the most important sequelae, may need artificial sphincters. CONCLUSIONS: Non-traumatic posterior urethral stenoses could be important complications, potentially compromising the outcomes of initial therapy. They could require complex surgeries leading to urinary incontinence.

Safety of vemurafenib in patients with BRAF V600 mutated metastatic melanoma: the Spanish experience.

OBJECTIVES: Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF V600 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 V600 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.

Blebbistatin-Loaded Poly(d,l-lactide-co-glycolide) Particles For Treating Arthrofibrosis.

Joint immobility is a debilitating complication of articular trauma that is characterized by thickening and stiffening of the joint capsule and the formation of fibrotic lesions inside joints. Capsule release surgery can temporarily restore mobility, but contraction often recurs due to the contractile activities of fibroblasts, which exert tension on the capsule ECM via nonmuscle myosin II. Based on these findings we hypothesized that blebbistatin, a drug that reversibly inhibits the activity of this protein, would relax ECM tension imposed by fibroblasts and reduce fibrosis. In this study, we characterized the effectiveness of blebbistatin as an anticontractile treatment. Given that sustained suppression of contractile activity may be required to achieve capsule release and reduce fibrosis, we compared the effects on fibroblast-mediated collagen ECM displacement of blebbistatin-loaded poly(lactide-co-gylcolide) (PLGA) particles versus bolus blebbistatin dosing. Time-lapse imaging of fluorescent microspheres embedded in collagen gels confirmed that PLGA/blebbistatin inhibited force generation and reduced both gel displacement and rate of displacement. In addition, collagen production at 10 days was significantly reduced. Taken together, these data indicate that blebbistatin-loaded PLGA particles can be used to inhibit fibroblast force-generation and reduce collagen production and lay the foundation for optimization of drug delivery technology for treating arthrofibrosis.

SEOM guidelines for the management of Malignant Melanoma 2015.

All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams.

Pedunculated polypoid melanoma. A case report of a rare spindle-cell variant of melanoma.

We report an 89-year-old man who presented with a slowly growing pigmented pedunculated tumor. The nodule was diagnosed as a spindle cell pedunculated malignant melanoma (PMM), a rare variant of spindle-cell malignant melanoma. The clinical presentation of this tumor and its histological and immunohistological features are discussed.

Development of a new oxygen consumption rate assay in cultures of Acanthamoeba (Protozoa: Lobosea) and its application to evaluate viability and amoebicidal activity in vitro.

A new fluorometric method has been developed for measuring the oxygen consumption rate (OCR) of Acanthamoeba cultures in microplates and for screening molecules with amoebicidal activity against this microorganism. The use of a biofunctional matrix (containing an oxygen-sensitive fluorogenic probe) attached to the microplate wells allowed continuous measurement of OCR in the medium, hence assessment of amoebic growth. The new OCR method applied to cell viability yielded a linear relationship and monitoring was much quicker than with indirect viability assays previously used. In addition, two drugs were tested in a cytotoxicity assay monitored by the new OCR viability test. With this procedure, the standard amoebicidal drug chlorhexidine digluconate showed an IC50 of 3.53 + 1.3 mg/l against Acanthamoeba polyphaga and 3.19 + 1.2 mg/l against Acanthamoeba castellanii, whereas a cationic dendrimer [G1Si(NMe3+)4] showed an IC50 of 6.42 + 1.3 mg/l against A. polyphaga. These data agree with previous studies conducted in our laboratory. Therefore, the new OCR method has proven powerful and quick for amoebicidal drug screening and is likely to be applied in biochemical studies concerning protozoa respiration and metabolism.

The nested variant of bladder transitional cell carcinoma: Review of 12 cases and review of the literature.

OBJECTIVES: The nested variant of bladder transitional cell carcinoma is extremely rare and has a different biological behavior to other bladder tumors. The aim of this study is to analize if their behavior is as aggressive as has been described in the literature. MATERIAL AND METHOD: Review of 12 diagnosed cases with nested variant of bladder transitional cell carcinoma and analysis of demographic characteristics, clinical presentation, tumor characteristics, treatment options, analysis of recurrence and cancer-specific survival between January 1997 and December 2010 in our hospital. RESULTS: 50% of the cases had a pathologic stage ≥T2, with grade of differentiation G2 (50%) or G3 (50%). After the pathological result of the TUR (transurethral resection) Bladder, 5 cases underwent radical cystoprostatectomy, 3 a second TUR bladder and 4 cases with treatment chemotherapy and/or radiotherapy (RT). Five out of 12 cases (41.7%) died due to bladder cancer and 3 died (25%) of other causes (urinary sepsis, respiratory failure, renal failure). With a median follow up of 40 months, the overall survival was 50% and cancer-specific survival of 65.6%. CONCLUSIONS: The nested variant of bladder transitional cell carcinoma is a disease with an advanced-stage presentation, with high recurrence and mortality rates despite the use of different treatments. So far there is not a clinical practice guideline for this variety of urothelial tumor.

Non-invasive 3D time-of-flight imaging technique for tumour volume assessment in subcutaneous models.

Subcutaneous tumour xenograft volumes are generally measured using callipers. This method is susceptible to inter- and intra-observer variability and systematic inaccuracies. Non-invasive 3D measurement using ultrasound and magnetic resonance imaging (MRI) have been considered, but require immobilization of the animal. An infrared-based 3D time-of-flight (3DToF) camera was used to acquire a depth map of tumour-bearing mice. A semi-automatic algorithm based on parametric surfaces was applied to estimate tumour volume. Four clay mouse models and 18 tumour-bearing mice were assessed using callipers (applying both prolate spheroid and ellipsoid models) and 3DToF methods, and validated using tumour weight. Inter-experimentalist variability could be up to 25% in the calliper method. Experimental results demonstrated good consistency and relatively low error rates for the 3DToF method, in contrast to biased overestimation using callipers. Accuracy is currently limited by camera performance; however, we anticipate the next generation 3DToF cameras will be able to support the development of a practical system. Here, we describe an initial proof of concept for a non-invasive, non-immobilized, morphology-independent, economical and potentially more precise tumour volume assessment technique. This affordable technique should maximize the datapoints per animal, by reducing the numbers required in experiments and reduce their distress.

Interobserver reliability of store-and-forward teledermatology in a clinical practice setting.

INTRODUCTION AND OBJECTIVES: Although many studies have evaluated the diagnostic reliability of store-and-forward (SF) teledermatology, the reliability of the technique for the diagnosis of general skin conditions in a clinical practice setting has never been demonstrated. We evaluated the reliability of SF teledermatology in clinical practice by analyzing the diagnostic agreement achieved in a subgroup of patients from the DERMATEL-2 study. MATERIAL AND METHODS: Patients referred from primary care settings were randomized to 3 groups: SF, a combination of videoconferencing and SF technology (VC-SF), and a control group. This article focuses on the SF group. Clinical data were recorded and photographs taken by primary care physicians, who forwarded the data electronically. Each SF consultation package was assessed by 3 dermatologists (D1,D2,D3). Subsequently all the patients were assessed by a single dermatologist (D1) in a face-to-face consultation. Finally, 2 other dermatologists (D4,D5) assessed the agreement between the diagnoses obtained by SF and FF. RESULTS: In total, 457 patients (200 males and 257 females) aged between 2 months and 86 years were randomized (192 to SF, 176 to VC-SF, and 89 to the control group). The diagnostic categories were as follows: tumors (49.4%), inflammatory (25.7%), adnexal (11%), infectious (9.4%) and other processes (4.4%) Since 170 patients had consultations deemed valid for analysis, the study included a total of 510 SF assessments. Most of the images and clinical records were of high quality (71.2% and 91.2% respectively), and diagnostic confidence was high in 81.4% of the cases studied. In 58.4% of cases the condition was managed exclusively by teledermatology. Levels of complete and aggregate interobserver agreement between SF and face-to-face evaluators were 0,72 and 0.90, respectively, for diagnosis and 0.61 and 0.80 for treatment. Diagnostic agreement correlated with the image quality (P < .001), diagnostic confidence (P<.001), felt need for conventional consultation (P<.001), and the quality of the clinical record (P=.013). CONCLUSION: The interobserver reliability of SF diagnosis in clinical practice is good. Dermatologists are able to predict errors in diagnosis by analyzing their own diagnostic confidence and evaluating the quality of the images.

Guidelines for biomarker testing in metastatic melanoma: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

This consensus statement, conceived as a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM), makes diagnostic and treatment recommendations for the management of patients with advanced or metastatic melanoma based on the current scientific evidence on biomarker use. This document thus provides an opportunity to improve healthcare efficiency and resource use, which will benefit these patients. Based on the data available so far, this expert group recommends routinely testing patients with metastatic melanoma for BRAF mutation status, as the result affects the subsequent therapeutic management of these patients. The analysis of genetic alterations in KIT may be reasonable in patients with primary tumours in acral or mucosal sites or on chronically sun-exposed skin, in an advanced condition, but not in patients with other types of melanomas. This panel believes that testing for other genetic alterations, such as NRAS mutation status in patients not carrying BRAF mutations, GNAQ/GNA11 mutational analysis or genetic alterations in PTEN, is not currently indicated as routine clinical practice, because the results do not influence treatment planning in these patients at the present time. Other important issues addressed in this document are the organisational requirements and quality controls needed for proper testing of these biomarkers, and the legal implications to be borne in mind.