Update on the management of older patients with pancreatic adenocarcinoma: a perspective from medical oncology.

In the context of pancreatic cancer, surgical intervention is typically recommended for localized tumours, whereas chemotherapy is the preferred approach in the advanced and/or metastatic setting. However, pancreatic cancer is closely linked to ageing, with an average diagnosis at 72 years. Paradoxically, despite its increased occurrence among older individuals, this population is often underrepresented in clinical studies, complicating the decision-making process. Age alone should not determine the therapeutic strategy but, given the high comorbidity and mortality of this disease, a comprehensive geriatric assessment (CGA) is necessary to define the best treatment, prevent toxicity, and optimize older patient care. In this review, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours (Grupo Español de Tratamiento de los Tumores Digestivos, TTD), and the Multidisciplinary Spanish Group of Digestive Cancer (Grupo Español Multidisciplinar en Cáncer Digestivo, GEMCAD) have assessed the available scientific evidence and propose a series of recommendations on the management and treatment of the older population with pancreatic cancer.

Incidence, risk factors, and evolution of venous thromboembolic events in patients diagnosed with pancreatic carcinoma and treated with chemotherapy on an outpatient basis.

BACKGROUND: Pancreatic carcinoma is one of the tumors associated with a higher risk for thromboembolic events, with incidence rates ranging from 5% to 41% in previous retrospective series. PATIENTS AND METHODS: We conducted a retrospective study in eleven Spanish hospitals that included 666 patients diagnosed with pancreatic carcinoma (any stage) between 2008 and 2011 and treated with chemotherapy. The main objective was to evaluate the incidence of venous thromboembolic events (VTE) in this population, as well as potential risk factors for thrombosis. The impact of VTE on mortality was also assessed. RESULTS: With a median follow-up of 9.3 months, the incidence of VTE was 22.1%; 52% were diagnosed incidentally. Our study was unable to confirm the ability of the Khorana score to discriminate between patients in the intermediate or high risk category for thrombosis. The presence of VTE proved to be an independent prognostic factor associated with increased risk of death (HR 2.39, 95% CI 1.96-2.92). Symptomatic events correlated with higher mortality than asymptomatic events (HR 1.72; 95% CI, 1.21-2.45; p = 0.002), but incidental VTE, including visceral vein thrombosis (VVT), negatively affected survival compared to patients without VTE. Subjects who developed VTE within the first 3 months of diagnosis of pancreatic carcinoma had lower survival rates than those with VTE after 3 months (HR 1.92, 95% CI 1.30-2.84; p<0.001). CONCLUSIONS: Pancreatic carcinoma is associated with a high incidence of VTE, which, when present, correlates with worse survival, even when thrombosis is incidental. Early onset VTE has a particularly negative impact.

Contribution and safety of the side-to-end hypoglossal-to-facial transfer in multidisciplinary facial reanimation.

BACKGROUND: This study evaluates facial and tongue function in patients undergoing side-to-end hypoglossal-to-facial transfer (HFT) with additional techniques. METHODS: Thirty-seven patients underwent a side-to-end HFT. Twelve had additional cross-face grafts, and 9 had an additional masseter-to-facial transfer. Facial was assessed with House-Brackmann (HB), Sunnybrook Facial Grading Scale (SFGS), and eFACE. Martins scale and the Oral-Pharyngeal Disability Index (OPDI) were used to assess tongue function. RESULTS: Ninety-four percent of cases reached HB grades III-IV. Mean total SFGS score improved from 16 ± 15 to 59 ± 11, while total eFACE score from 52 ± 13 to 80 ± 5. Dual nerve transfers were a predictor for a better eFACE total score p = 0.034, ß = 2.350 [95% CI, 0.184-4.516]), as well as for a higher SFGS total score (p = 0.036, ß = 5.412 [95% CI, 0.375-10.449]). All patients had Martin's grade I. Mean postoperative OPDI scores were 84 ± 17 (local physical), 69 ± 16 (simple and sensory motor components), 82 ± 14 (complex functions), and 73 ± 22 (psychosocial). CONCLUSIONS: The side-to-end HFT offers predictable facial function outcome and preserves tongue function in nearly all cases. Dual nerve transfers appear to improve the final outcome.

6-Amino-3-Methyl-4-(2-nitrophenyl)-1,4-Dihydropyrano[2,3-c]Pyrazole-5-Carbonitrile Shows Antihypertensive and Vasorelaxant Action via Calcium Channel Blockade.

Several 4H-pyran derivatives were designed and synthesized previously as vasorelaxant agents for potential antihypertensive drugs. In this context, the objective of the present investigation was to determine the functional mechanism of vasorelaxant action of 6-amino-3-methyl-4-(2-nitrophenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1: ) and its in vivo antihypertensive effect. Thus, compound 1: showed significant vasorelaxant action on isolated aorta rat rings pre-contracted with serotonin or noradrenaline, and the effect was not endothelium-dependent. Compound 1: induced a significant relaxant effect when aortic rings were contracted with KCl (80 mM), indicating that the main mechanism of action is related to L-type calcium channel blockade. Last was corroborated since compound 1: induced a significant concentration-dependent lowering of contraction provoked by cumulative CaCl2 adding. Moreover, compound 1: was capable to block the contraction induced by FPL 64176, a specific L-type calcium channel agonist, in a concentration-dependent manner. On the other hand, docking studies revealed that compound 1: interacts on two possible sites of the L-type calcium channel and it had better affinity energy (-7.80+/-0.00 kcal/mol on the best poses) than nifedipine (-6.86+/-0.14 kcal/mol). Finally, compound 1: (50 mg/kg) showed significant antihypertensive activity, lowering the systolic and diastolic blood pressure on spontaneously hypertensive rats (SHR) without modifying heart rate.

Exploring novel capping framework: high substituent pyridine-hydroxamic acid derivatives as potential antiproliferative agents.

PURPOSE: Histone deacetylases (HDACs) play a vital role in the epigenetic regulation of gene expression due to their overexpression in several cancer forms. Therefore, these enzymes are considered as a potential anticancer drug target. Different synthetic and natural structures have been studied as HDACs inhibitors; based on available structural design information, the capping group is important for the biological activity due to the different interactions in the active site entrance. The present study aimed to analyze high substituted pyridine as a capping group, which included carrying out the synthesis, antiproliferative activity analysis, and docking studies of these novel compounds. METHODS: To achieve the synthesis of these derivatives, four reaction steps were performed, generating desired products 15a-k. Their effects on cell proliferation and gene expression of p21, cyclin D1, and p53 were determined using the sulphorhodamine B (SRB) method and quantitative real-time polymerase chain reaction. The HDAC1, HDAC6, and HDAC8 isoforms were used for performing docking experiments with our 15a-k products. RESULT: The products 15a-k were obtained in overall yields of 40-71%. Compounds 15j and 15k showed the highest antiproliferative activity in the breast (BT-474 and MDA-MB-231) and prostate (PC3) cancer cell lines at a concentration of 10 µM. These compounds increased p21 mRNA levels and decreased cyclin D1 and p53 gene expression. The docking study showed an increment in the strength, and in the number of interactions performed by the capping moiety of the tested molecules compared with SAHA; interactions displayed are mainly van der Waals, π-stacking, and hydrogen bond. CONCLUSION: The synthesized compounds 2-thiophene (15j) and 2-furan (15k) pyridine displayed cell growth inhibition, regulation of genes related to cell cycle progression in highly metastatic cancer cell lines. The molecular coupling analysis performed with HDAC1, HDAC6 and HDAC8 showed an increment in the number of interactions performed by the capping moiety and consequently in the strength of the capping group interaction.

Quiste intraneural del nervio supraescapular: causa atípica de síndrome de atrapamiento de nervio periférico. Presentación de un caso y revisión de la literatura / Intraneural cyst of the supraescapular nerve: Atypical cause of peripheral nerve entrapment syndrome. Case report and literature review

Objetivo: Los quistes intraneurales son lesiones benignas de contenido mucinoso que se ubican dentro del epineuro de algunos nervios periféricos, de etiopatogenia controvertida. La mayoría se localizan a nivel de los miembros inferiores. Cuando aparece en los miembros superiores, el nervio más frecuentemente afectado es el cubital. De extraordinaria infrecuencia es el síndrome de atrapamiento del nervio supraescapular debido a la formación de un quiste intraneural del mismo. Con este artículo, aportamos un nuevo caso y realizamos una revisión de la literatura de los quistes intraneurales localizados en el nervio supraescapular. Métodos: Presentamos el caso de una paciente de 49 años con dolor en región lateral del hombro de varios meses de evolución. Se realizó RM plexo braquial donde se objetivó una tumoración de aproximadamente 2×1,5cm, de aspecto quístico, en relación al tronco superior del plexo braquial derecho. Resultados: Fue intervenida bajo control neurofisiológico, mediante un abordaje supra-infraclavicular. La tumoración quística afectaba a la extensión del nervio supraescapular. Tras localizar una zona en la superficie libre de fascículo nervioso se procedió a la disección, vaciamiento del quiste con contenido gelatinoso xantocrómico y resección parcial de la capsula. El examen anatomopatológico confirmó el diagnóstico de quiste intraneural (ganglión). Conclusión: El nervio supraescapular es un nervio mixto que procede del tronco superior. Proporciona las ramas motoras al músculo supraespinoso e infraespinoso, y puede derivar, resultado de la compresión, en una atrofia de los mismos. Es importante conocer esta entidad que, aún de extraordinaria infrecuencia, es uno de los diagnósticos diferenciales que deben ser tenidos en cuenta al estudiar un paciente con dolor irradiado al hombro, y su tratamiento correcto redunda muchas veces en la remisión completa de la sintomatología

Objective: Intraneural cysts are benign lesions located within the epineurium of some peripheral nerves and their aetiopathogenesis is controversial. Most are located at the level of the lower limbs. In the upper limbs, the most frequently affected nerve is the ulnar nerve. Suprascapular nerve entrapment syndrome due to the formation of an intraneural cyst is rare. In this article, we show a new case and perform a literature review of intraneural cysts located in the suprascapular nerve. Methods: We present a 49-year-old woman with pain in the lateral shoulder region of several months’ evolution. A brachial plexus MR showed a tumour of approximately 2×1.5cm, with a cystic appearance, in relation to the upper trunk of the right brachial plexus. Results: We used a supra-infraclavicular approach. The cystic tumour affected the suprascapular nerve. After locating a zone on the surface without nervous fascicles, we performed a partial resection of the capsule and emptying of the cyst, with a xanthochromic gelatinous content. The anatomopathological examination confirmed the diagnosis of intraneural cyst. Conclusion: The suprascapular nerve is a mixed nerve, coming from the upper trunk. It provides the motor branches to the supraspinatus and infraspinatus muscle. Compression of the suprascapular nerve leads to atrophy of these muscles. This entity is one of the differential diagnoses in a patient with pain irradiating to the shoulder, and its correct treatment often results in complete remission of symptoms

Intraneural cyst of the supraescapular nerve: Atypical cause of peripheral nerve entrapment syndrome. Case report and literature review. / Quiste intraneural del nervio supraescapular: causa atípica de síndrome de atrapamiento de nervio periférico. Presentación de un caso y revisión de la literatura.

OBJECTIVE: Intraneural cysts are benign lesions located within the epineurium of some peripheral nerves and their aetiopathogenesis is controversial. Most are located at the level of the lower limbs. In the upper limbs, the most frequently affected nerve is the ulnar nerve. Suprascapular nerve entrapment syndrome due to the formation of an intraneural cyst is rare. In this article, we show a new case and perform a literature review of intraneural cysts located in the suprascapular nerve. METHODS: We present a 49-year-old woman with pain in the lateral shoulder region of several months' evolution. A brachial plexus MR showed a tumour of approximately 2×1.5cm, with a cystic appearance, in relation to the upper trunk of the right brachial plexus. RESULTS: We used a supra-infraclavicular approach. The cystic tumour affected the suprascapular nerve. After locating a zone on the surface without nervous fascicles, we performed a partial resection of the capsule and emptying of the cyst, with a xanthochromic gelatinous content. The anatomopathological examination confirmed the diagnosis of intraneural cyst. CONCLUSION: The suprascapular nerve is a mixed nerve, coming from the upper trunk. It provides the motor branches to the supraspinatus and infraspinatus muscle. Compression of the suprascapular nerve leads to atrophy of these muscles. This entity is one of the differential diagnoses in a patient with pain irradiating to the shoulder, and its correct treatment often results in complete remission of symptoms.

Liposarcoma mixoide de células redondas de plexo braquial / Myxoid/round cell liposarcoma of the brachial plexus

El liposarcoma mixoide de células redondeadas es un tumor habitualmente originado de partes blandas, que raramente encuentra su origen en el plexo braquial. Presentamos un caso muy infrecuente de liposarcoma mixoide de células redondeadas de plexo braquial que fue intervenido quirúrgicamente y que evolucionó favorablemente y sin focalidad neurológica tras 2 años de seguimiento. Es el primer caso publicado de esta estirpe oncológica originado en el plexo braquial

Myxoid/round cell liposarcoma is a soft tissue sarcoma that is extremely rare in the brachial plexus. We report a case of a myxoid/round cell liposarcoma originating in the brachial plexus that was surgically resected and evolved well, with no deficit or recurrence after 2 years of follow-up. To date, there has been no other case of this sarcoma in the literature

[Myxoid/round cell liposarcoma of the brachial plexus]. / Liposarcoma mixoide de células redondas de plexo braquial.

Myxoid/round cell liposarcoma is a soft tissue sarcoma that is extremely rare in the brachial plexus. We report a case of a myxoid/round cell liposarcoma originating in the brachial plexus that was surgically resected and evolved well, with no deficit or recurrence after 2 years of follow-up. To date, there has been no other case of this sarcoma in the literature.

The effects of porosity on optical properties of semiconductor chalcogenide films obtained by the chemical bath deposition.

This paper is dedicated to study the thin polycrystalline films of semiconductor chalcogenide materials (CdS, CdSe, and PbS) obtained by ammonia-free chemical bath deposition. The obtained material is of polycrystalline nature with crystallite of a size that, from a general point of view, should not result in any noticeable quantum confinement. Nevertheless, we were able to observe blueshift of the fundamental absorption edge and reduced refractive index in comparison with the corresponding bulk materials. Both effects are attributed to the material porosity which is a typical feature of chemical bath deposition technique. The blueshift is caused by quantum confinement in pores, whereas the refractive index variation is the evident result of the density reduction. Quantum mechanical description of the nanopores in semiconductor is given based on the application of even mirror boundary conditions for the solution of the Schrödinger equation; the results of calculations give a reasonable explanation of the experimental data.

Effect of recombinant human growth hormone on peripheral nerve regeneration: experimental work on the ulnar nerve of the rat.

Neurotrophic factors may be used to improve the growth and repair of injured peripheral nerves. In this study we determined the effectiveness of recombinant human growth hormone on peripheral nerve injury in the Wistar rat. The ulnar nerve of the rat was sectioned and its proximal and distal ends were sutured to either end of a silastic tube, with the aim of encouraging regeneration through the tube. 32 ulnar nerve specimens were randomized into two groups: 18 nerves regenerating under the influence of recombinant growth hormone, and 14 nerves regenerating in its absence. The study was performed over a period of 8 weeks and progression of regeneration was assessed with regular surface electroneurography every 1-2 weeks after surgery. In the group receiving recombinant growth hormone, it comprised a significant improvement in the recovery of conduction velocity, and a more gradual increase in the amplitude of motor potential from the fifth week onwards was observed. Histological analysis of study specimens in the recombinant hormone group revealed an improved architecture of the regenerating nerve, a greater density of nerve fibers, and increased myelination with a lesser degree of endoneural fibrosis. Our work demonstrates the positive effect of the administration of recombinant human growth hormone in obtaining significantly improved conduction velocities, and a greater improvement in nerve regeneration from the fifth week of monitoring when compared to the control group. Histological analysis in the group receiving hormone showed acceptable degree of myelination with little granulation tissue and fibrosis.

Papel de las células satélite en la hipertrofia y regeneración muscular en respuesta al ejercicio / Role of satellite cells on muscle hypertrophy and muscle in response to exercise

Desde el descubrimiento de las células satélite 1961 han sido numerosos los estudios sobre el papel de estas células en la regeneración muscular y en la respuesta hipertrófica del músculo esquelético humano. El interés por estas células se ha visto incrementado recientemente ya que podrían convertirse en vehículo de técnicas de terapia celular. En este trabajo de revisión describimos especialmente las respuestas a diferentes estímulos de ejercicio en las que participan las células satélite. El contenido de núcleos de células satélite en los músculos esqueléticos humanos oscila entre un 1 y un 7% del total núcleos celulares observables en una preparación de músculo esquelético. El ejercicio regular parece asociarse a un aumento del contenido total de núcleos celulares y de núcleo de células satélite, mientras que con la edad disminuye su número. Así pues, es probable que la práctica regular de ejercicio físico sirva para contrarrestarlos cambios producidos en el “pool” de células satélite con la edad, provocando una mejora en el “pool” que puede ser sostenida en el tiempo. El uso de esteroides anabolizantes también está relacionado con un mejor contenido mío nuclear por sección transversal en culturistas. Sin embargo, no se sabe cuáles el tipo de ejercicio y qué duración e intensidad ofrece mejores resultados, en términos de aumento del número de células satélite. Menos se sabe aún de los factores que determinan la incorporación de núcleos de células satélite a fibras musculares ya existentes, fenómeno que es facilitado por actividad física regular. Tampoco se sabe si la combinación de mío trauma (lesión deportiva, por ejemplo) con ejercicio en la fase de recuperación puede redundar en una mayor y eficaz activación de las células satélite (AU)

Since the discovery of the satellite cells in 1961 a number of studies have examined the role that these cells play on muscle hypertrophy and regeneration, and on the hypertrophy responseto strength training in humans. The interest for these cells has raised in the last years due to the fact that they could be used as a vehicle in techniques of cellular therapy. The following review describes some of the elicited by physical activity on the satellite cells and how these satellite cells may contribute to muscle hypertrophy and regeneration. The content of nuclei pertaining to satellite cells among the overall nuclei content in a muscle histological preparation ranges between1 and 7%. Regular physical activity has been associated with both and enhancement of the total number of nuclei and increase of the content of satellite cells. In contrast, ageing is associated with a reduced proportion of nuclei pertaining to satellite cells. The latter, may be attenuated by regular participation on exercise, although there is no definitive scientific evidence for this effect. Anabolic steroid abuse has been associated with increased content of satellite cells in bodybuilders. It remains unknown, however, what the kind, duration and intensity of exercise more appropriate to stimulate satellite cell activation, proliferation and differentiation. Less is even known about the mechanisms that govern the process of fusion and incorporation of satellite cells with pre-existing muscle fibers, although some experimental evidences suggest that this process is facilitated by regular physical activity. More studies are need to verify if the combination of my trauma (sport injury, for example) and exercise during the recovery phase after an injury results in a greater stimulation of the f the satellite cells and in a more efficient reparation (AU)