Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas

To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas. Research included the following electronic databases: PUBMED, EMBASE, LILACS and The Cochrane Collaboration Controlled Trials Register. All published studies involving the antitumoral effects (cellular and molecular mechanisms) of cannabinoids were considered for this review. The bibliography search strategy included all publications of each of these databases until December 31, 2012. From 2,260 initially identified articles, 35 fulfilled the inclusion criteria for this review. All the studies included in this systematic review were experimental (in vivo and/or in vitro), except for one pilot clinical trial phase I/II involving humans. In all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors. The antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects. Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects. Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected. The safety factor in the cannabinoids’ administration has also been demonstrated in vivo. The various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo. These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.     

Considerations on pancreatic exocrine function after pancreaticoduodenectomy

The pancreaticoduodenectomy (PD) procedure may lead to pancreatic exocrine and endocrine insufficiency. There are several types of reconstruction for this kind of operation. Pancreaticogastrostomy (PG) was introduced to reduce the rate of postoperative pancreatic fistula. Although some randomized control trials have shown no differences regarding pancreatic leakage between PG and pancreaticojejunostomy (PJ), recently some reports reveal benefits from the PG over the PJ. Some surgeons concern about the performing of the PG and inactivation of pancreatic enzymes being in contact with the gastric juice, and the detrimental results over the exocrine pancreatic function. The pancreatic exocrine function can be measured with direct and indirect tests. Direct tests have the highest sensitivity and specificity for detection of exocrine insufficiency but require tube placement. Among the tubeless indirect tests, the van de Kamer stool fat analysis remains the standard to diagnose fat malabsorption. The patient compliance and time consuming makes it not so suitable for its clinical use. Fecal immunoreactive elastase test is employed for screening of exocrine insufficiency, is not cumbersome, and has been used to study pancreatic function after resection. We analyze the FE1 levels in our patients after the PD with two types of reconstruction, PG and PJ, and we discuss some considerations about the pancreaticointestinal drainage method after pancreaticoduodenectomy.     

Systematic review of efficacy and safety of pemetrexed in non-small-cell-lung cancer

Introduction Lung cancer accounts for 20 % of cancer deaths in Spain. The most frequent subtype (87 %) is non-small cell lung cancer (NSCLC). Pemetrexed is a recently marketed drug added to NSCLC therapeutic arsenal. It seems to have become one of the most used options for the treatment of this condition over the last 3 years. Aim of the review To evaluate the efficacy and safety of pemetrexed in NSCLC, in the different therapy lines. Method A systematic search of published literature was conducted using the main databases (MEDLINE, EMBASE, the Cochrane Library and the Center for Reviews and Dissemination) and subsequently a search of referenced literature was performed. We included clinical trials, meta-analyses and systematic reviews. The evaluation of the quality of the articles was performed by pairs using specific assessment scales, Critical Appraisal Skills Program (CASP) adapted for CASP Spain. Then we extracted data on efficacy and safety according to the treatment line assessed. Results We identified 277 references. Finally, nine clinical trials and a meta-analysis complied with inclusion criteria. In first-line induction, treatment with pemetrexed associated with a platinum was similar in terms of efficacy to other alternative chemotherapy regimens, except in patients with non-squamous histology, in whom survival was higher in the experimental group. In maintenance treatment, greater efficacy was seen with pemetrexed in patients with non-squamous histology. In second-line treatment, there were no significant differences in terms of efficacy and safety for pemetrexed treatment versus other chemotherapy options. The most frequent adverse reactions were: hematological, gastrointestinal and neurological. All were significantly less frequent with pemetrexed versus other alternative therapies, except for liver toxicity. Conclusions Due to the high degree of uncertainty as to its efficacy in certain subgroups of patients, including conflicting data; to its recent incorporation, and therefore lack of safety data in the medium and long term, and the high budgetary impact of its incorporation into health systems, it seems reasonable to optimize its use, identifying those patients who may benefit most.     

Genetic imbalances detected by multiplex ligation-dependent probe amplification in a cohort of patients with oral squamous cell carcinoma—the first step towards clinical personalized medicine

Oral tumors are a growing health problem worldwide; thus, it is mandatory to establish genetic markers in order to improve diagnosis and early detection of tumors, control relapses and, ultimately, delineate individualized therapies. This study was the first to evaluate and discuss the clinical applicability of a multiplex ligation-dependent probe amplification (MLPA) probe panel directed to head and neck cancer. Thirty primary oral squamous cell tumors were analyzed using the P428 MLPA probe panel. We detected genetic imbalances in 26 patients and observed a consistent pattern of distribution of genetic alterations in terms of losses and gains for some chromosomes, particularly for chromosomes 3, 8, and 11. Regarding the latter, some specific genes were highlighted due to frequent losses of genetic material—RARB, FHIT, CSMD1, GATA4, and MTUS1—and others due to gains—MCCC1, MYC, WISP1, PTK2, CCND1, FGF4, FADD, and CTTN. We also verified that the gains of MYC and WISP1 genes seem to suggest higher propensity of tumors localized in the floor of the mouth. This study proved the value of this MLPA probe panel for a first-tier analysis of oral tumors. The probemix was developed to include target regions that have been already shown to be of diagnostic/prognostic relevance for oral tumors. Furthermore, this study emphasized several of those specific genetic targets, suggesting its importance to oral tumor development, to predict patients’ outcomes, and also to guide the development of novel molecular therapies.     

Outcomes of pediatric living donor kidney transplantation: A single‐center experience

Renal transplantation is the treatment of choice for children with ESRD offering advantages of improved survival, growth potential, cognitive development, and quality of life. The aim of our study was to compare the outcomes of LDKT vs DDKT performed in children at a single center. Retrospective chart review of pediatric patients who underwent kidney transplantation from 2005 to 2014 was performed. Ninety‐one renal transplants were accomplished, and 31 cases (38.27%) were LDKT, and in 96.7% of the cases, the graft was obtained through laparoscopy. Thirty‐four receptors weighted <25 kg. LDKT group had statistically significant lower cold ischemia times than DDKT one. Complication rate was 9.67% for LDKT and 18.33% for DDKT. eGFR was better in LDKT. Patient survival rate was 100% for LDKT and 98.3% for DDKT, and graft survival rate was 96.7% for LDKT and 88.33%‐80% for DDKT at a year and 5 years. Our program of pediatric kidney transplantation has achieved optimal patient and graft survival rates with low rate of complications. Living donor pediatric kidney transplants have higher patient and better graft survival rates than deceased donor kidney transplants.     

Feeding Jejunostomy after esophagectomy cannot be routinely recommended. Analysis of nutritional benefits and catheter-related complications

Background

Patients undergoing esophagectomy for cancer usually deal with malnourishment which increases postoperative morbimortality. The objective of this paper is to analyze the nutritional benefits of feeding jejunostomy (FJ) for early postoperative enteral nutrition (EN) and directly-related complications.

Premature ventricular contractions of the right ventricular outflow tract: Upward displacement of the ECG unmasks ST elevation in V1 associated with the presence of low voltage areas

Introduction and Aims

Frequent premature ventricular contractions (PVCs) originating from the right ventricular outflow tract (RVOT) are usually considered a benign entity and the ECG is typically normal. The aim of this study was to assess whether upward displacement of the ECG to the second intercostal space (ICS) would reveal any abnormal pattern.

Lessons from glaucoma: rethinking the fluid-brain barriers in common neurodegenerative disorders

Glaucoma has been recently characterized as a member of the group of anoikis-related diseases. Anoikis, a form of apoptosis, can be triggered by the unfastening of adherent junctions present in astrocytes. In those areas of the central nervous system in which the soma of the neurons or their axons and dendrites are metabolically dependent on the activity of astrocytes, a derangement of the lactate shuttle caused by a separation between the plasma membranes of neurons and astrocytes would result in metabolic impairment of the neurons themselves. In glaucoma, the triggering event has been attributed to the posterior deviation of aqueous humor towards the astrocyte-rich prelaminar tissue of the optic nerve head. The mean calcium content in the aqueous is able to interfere with calcium-dependent adherent junctions and induce anoikis of the astrocytes. As the cerebrospinal fluid has a similar base calcium concentration, a shunt of cerebrospinal fluid through the cerebral parenchyma would be able to interfere in the astrocytic architecture with dire consequences to the metabolically dependent neurons. Here the similitude between glaucoma,amyotrophic lateral sclerosis and Alzheimer's disease are discussed and the concept of the break in the fluid-brain barrier, as an event separated from the blood-brain barrier, is stressed.