A randomized trial comparing transanal irrigation and percutaneous tibial nerve stimulation in the management of low anterior resection syndrome.

AIM: To assess the effectiveness of transanal irrigation (TAI) compared with posterior tibial nerve stimulation (PTNS) in severe and chronic low anterior resection syndrome (LARS). METHOD: A two-group parallel, open-label randomized controlled trial carried out in a single university hospital. The study population included patients with a LARS scale score of more than 29 points who had undergone rectal surgery more than 1 year previously. These were randomly allocated, with a central randomization system, following a 1:1 sequence to TAI or PTNS. The main study outcome was to achieve a reduction of at least one LARS grade in at least 50% of the patients, for each intervention. RESULTS: A total of 27 patients (TAI = 13, PTNS = 14) were randomized. Both groups were similar with regard to confounding factors. Four patients were excluded because of intercurrent disease or early dropout, leaving 23 (TAI, n = 10; PTNS, n = 13) for analysis. Eight out of 10 and 4 out of 13 patients were downgraded with TAI and PTNS, respectively. The median LARS score decreased from 35 [interquartile range (IQR) 32-39] to 12 (IQR 12-26) (P = 0.021) for the TAI group and from 35 (IQR 34-37) to 30 (IQR 25-33) (P = 0.045) for the PTNS group. The Vaizey score fell from 15 (IQR 11-18) to 6 (IQR 4-7) (P = 0.037) and from 14 (IQR 13-17) to 9 (IQR 7-10) (P = 0.007) with TAI and PTNS, respectively, with 80% and 38% of patients, respectively, showing decreases of more than 50%. Improvement in quality of life was observed in both groups. CONCLUSION: Both treatments improved the LARS score in this study but this was only significant in the TAI group.

Non-inferiority multicenter prospective randomized controlled study of rectal cancer T2-T3s (superficial) N0, M0 undergoing neoadjuvant treatment and local excision (TEM) vs total mesorectal excision (TME).

PURPOSE: The standard treatment of rectal adenocarcinoma is total mesorectal excision (TME), in many cases requires a temporary or permanent stoma. TME is associated with high morbidity and genitourinary alterations. Transanal endoscopic microsurgery (TEM) allows access to tumors up to 20 cm from the anal verge, achieves minimal postoperative morbidity and mortality rates, and does not require an ostomy. The treatment of T2, N0, and M0 cancers remains controversial. Preoperative chemoradiotherapy (CRT) in association with TEM reduces local recurrence and increases survival. The TAU-TEM study aims to demonstrate the non-inferiority of the oncological outcomes and the improvement in morbidity and quality of life achieved with TEM compared with TME. METHODS: Prospective, multicenter, randomized controlled non-inferiority trial includes patients with rectal adenocarcinoma less than 10 cm from the anal verge and up to 4 cm in size, staged as T2 or T3-superficial N0-M0. Patients will be randomized to two areas: CRT plus TEM or radical surgery (TME). Postoperative morbidity and mortality will be recorded and patients will complete the quality of life questionnaires before the start of treatment, after CRT in the CRT/TEM arm, and 6 months after surgery in both arms. The estimated sample size for the study is 173 patients. Patients will attend follow-up controls for local and systemic relapse. CONCLUSIONS: This study aims to demonstrate the preservation of the rectum after preoperative CRT and TEM in rectal cancer stages T2-3s, N0, M0 and to determine the ability of this strategy to avoid the need for radical surgery (TME). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01308190. Número de registro del Comité de Etica e Investigación Clínica (CEIC) del Hospital universitario Parc Taulí: TAU-TEM-2009-01.

Treatment of anastomotic leaks with metallic stent after esophagectomies.

The diagnosis and the treatment of anastomotic leak after esophagectomy are the keys to reduce the morbidity and mortality after this surgery. The stent plays an important role in the treatment of the leakage and in the prevention of reoperation. We have analyzed the database of the section of the esophagogastric surgery of Donostia University Hospital from June 2003 to May 2012. It is a retrospective study of 113 patients with esophagectomy resulting from tumor, and 24 (21.13%) of these patients developed anastomotic leak. Of these 24 patients, 13 (54.16%) have been treated with a metallic stent and 11 (45.84%) without a stent. The average age of the patients was 55.69 and 62.45 years, respectively. All patients treated with and without a stent have been males. Eight (61.5%) stents were placed in the neck and five (38.5%) in the chest. However, among the 11 fistulas treated without a stent, 9 patients had cervical anastomosis (81.81%) and 2 patients (18.18%) had anastomosis in the chest. Twelve patients (92.30%) with a stent preserve digestive continuity, and 10 patients (90.90%) were treated without a stent. One patient died in the stent group and one in the nonstent group. The treatment with metallic stent of the anastomotic leak after esophagectomy is an option that can prevent reoperation in these patients, but it does not decrease the average of the hospital stay. The stent may be more useful in thoracic anastomotic leaks.

Intrapelvic placement of a breast implant to allow deferred ileoanal pouch anastomosis after emergency proctocolectomy.

Restoration of intestinal continuity at a second stage after emergency total proctocolectomy may be difficult or hazardous due to the pelvic cavity being closed off. We present a way of keeping the pelvic cavity open and accessible following total proctocolectomy by insertion of a breast implant that hinders fibrosis and prevents intestinal loops from occupying the space. A 275 ml silicone breast implant was placed in the pelvic cavity after total proctocolectomy and closure of the rectal stump. Three months after the initial surgery, the breast implant had kept the pelvic cavity open, facilitating identification of the rectal stump and creation of an ileoanal J-pouch at this second stage. The use of a breast implant to fill the pelvic cavity may facilitate restoration of intestinal continuity in second-stage surgery and thereby decrease the number of associated complications.

Meta-analysis of randomized controlled trials comparing different techniques with primary closure for chronic pilonidal sinus.

BACKGROUND: There are different open healing and primary closure approaches for chronic pilonidal sinus (CPD) that differ in principles and extension. AIMS: To compare the results of different closure surgical techniques, we performed a meta-analysis of randomized controlled trials (RCT) comparing: (1) open wide excision versus open limited excision (sinusectomy) or unroofing (sinotomy); (2) midline closure (conventional and tension-free) versus off-midline; (3) advancing versus rotation flaps; and (4) sinusectomy/sinotomy versus primary closure. METHODS: Data extraction and risk of bias assessment were conducted independently by the authors using the Cochrane Collaboration's tool. Data were pooled using fixed and random-effects models. Primary outcomes were rate of healing, recurrence, wound infection and dehiscence. Twenty-five trials (2,949 patients) were included. RESULTS: Four trials compared limited versus radical open healing. Although recurrence rate did not differ, all other outcomes favored the limited approach. Ten studies compared midline versus off-midline primary closure; wound infection and dehiscence were significantly higher after midline closure. Six RCT compared Karydakis/Bascom versus Limberg. No difference was found in recurrence or wound complications rate. Six RCT compared sinusectomy/sinotomy versus primary closure. Recurrence rate was significantly lower after sinusectomy/sinotomy; no significant differences were found in other outcomes. CONCLUSION: Our meta-analysis suggest that some of the questions of which is the best surgical technique for CPD have now been answered: open radical excision and primary midline closure should be abandoned. Sinusotomy/sinectomy or en bloc resection with off midline primary closure are the preferred approaches.

SUMO-1 transiently localizes to Cajal bodies in mammalian neurons.

Cajal bodies (CBs) are nuclear organelles involved in the maturation of small nuclear ribonucleoproteins required for the processing of pre-mRNAs. They concentrate coilin, splicing factors and the survival of motor neuron protein (SMN). By using immunocytochemistry and transfection experiments with GFP-SUMO-1, DsRed1-Ubc9, GFP-coilin and GFP-SMN constructs we demonstrate the presence of SUMO-1 and the SUMO conjugating enzyme (Ubc9) in a subset of CBs in undifferentiated neuron-like UR61 cells. Furthermore, SUMO-1 is transiently localized into neuronal CBs from adult nervous tissue in response to osmotic stress or inhibition of methyltransferase activity. SUMO-1-positive CBs contain coilin, SMN and small nuclear ribonucleoproteins, suggesting that they are functional CBs involved in pre-mRNA processing. Since coilin and SMN have several putative motifs of SUMO-1 modification, we suggest that the sumoylation of coilin and/or SMN might play a role in the molecular reorganization of CBs during the neuronal differentiation or stress-response.

Nuclear organization and dynamics of transcription sites in rat sensory ganglia neurons detected by incorporation of 5'-fluorouridine into nascent RNA.

In this study we have used the transcription assay with 5'-fluorouridine incorporation into nascent RNA to analyze the nuclear organization and dynamics of transcription sites in rat trigeminal ganglia neurons. The 5'-FU administrated by i.p. injection was successfully incorporated into nuclear domains containing actively transcribing genes of trigeminal neurons. 5'-Fluorouridine RNA-labeling was detected with immunocytochemistry at light and electron microscopy levels. The 5'-fluorouridine incorporation sites were detected in the nucleolus, particularly on the dense fibrillar component, and in numerous transcription foci spread throughout the euchromatin regions, without preferential positioning at the nuclear periphery or in the nuclear interior. Double labeling experiments to combine 5'-fluorouridine incorporation with molecular markers of nuclear compartments showed the absence of transcription sites in Cajal bodies and nuclear speckles of splicing factors. Similarly, no 5'-fluorouridine labeling was detected in well-characterized chromatin silencing domain, the telomeric heterochromatin. The specificity and sensitivity of the run-on transcription assay in trigeminal ganglia neurons was verified by the i.p. administration of the transcription inhibitor actinomycin D. The dramatic reduction in RNA synthesis upon actinomycin D treatment was associated with two important cellular events, heterochromatin silencing and formation of DNA damage/repair nuclear foci, demonstrated by the expression of tri-methylated histone H4 and phosphorylated H2AX, respectively. 5'-Fluorouridine incorporation in animal models provides a useful tool to investigate the organization of gene expression in mammalian neurons in both normal physiology and experimental pathology systems.

The origin and differentiation of microglial cells during development.

Some authors claim that microglia originate from the neuroepithelium, although most now believe that microglial cells are of mesodermal origin, and probably belong to the monocyte/macrophage cell line. These cells must enter the developing central nervous system (CNS) from the blood stream, the ventricular space or the meninges. Afterward microglial cells are distributed more or less homogeneously through the entire nervous parenchyma. Stereotyped patterns of migration have been recognized during development, in which long-distance tangential migration precedes radial migration of individual cells. Microglial cells moving through the nervous parenchyma are ameboid microglia, which apparently differentiate into ramified microglia after reaching their definitive location. This is supported by the presence of cells showing intermediate features between those of ameboid and ramified microglia. The factors that control the invasion of the nervous parenchyma, migration within the developing CNS and differentiation of microglial cells are not well known. These phenomena apparently depend on environmental factors such as soluble or cell-surface bound molecules and components of the extracellular matrix. Microglial cells within the developing CNS are involved in clearing cell debris and withdrawing misdirected or transitory axons, and presumably support cell survival and neurite growth.

[Clinical management of terrorist bomb explosions]. / Atención a las víctimas por ataque terrorista con explosivos.

At 07:39 on 11 March 2004 terrorist bomb explosions ocurred in 4 trains in Madrid killing 177 people instantly and 14 more later in the hospital. This report describes the organization, clinical management and patterns of injuries in casualties who were taken to our chil-patients were taken to the Gregorio Marañon hospital and 12 to the children's one. The mean age was 16 years (14-21), Two of them were critically ill and needed intensive care (ITP 5). Tympanic perforations occurred in 81% victims with moderate to severe trauma, shrapnel wounds in 36% and eye lesions in 27%. Among critically ill patients blast lung injury, cranial and abdominal trauma were the most important lesions. Training in AITP courses and hospital logistics were essential in clinical management of these casualties.

Paediatric trauma in Spain: a report from the HUGM Trauma Registry.

OBJECTIVES: To analyse the characteristics of the infant population suffering trauma in our setting. To evaluate the importance of the different aetiological mechanisms. To study the pre- and intra-hospital management of these children. To describe the relative significance of the different lesions. To establish the magnitude of paediatric trauma as a social problem in terms of morbidity and mortality. MATERIAL AND METHODS: From January 1995 to April 2002, a total of 2633 children admitted to our Centre (Hospital Universitario Gregorio Maranon) after suffering some type of injury were included in our Trauma Register. 108 variables have been analysed, including the identification of the patient, type, site and mechanism of the accident, pre-hospital care, transport, complete evaluation on admission, indices of injury severity, diagnostic tests, lesions, treatments performed and morbidity and mortality. RESULTS: The accidents were more frequent in boys than in girls (68.5 % versus 31.5 %). The predominant age group was the 12 - 15 year old group (36.8 %). There was a higher frequency of accidents in the street (37.2 %) than at home (19.4 %) or at school (13.8 %). The most frequent mechanism was a fall (35.6 %), followed by road traffic accidents (23.7 %). On admission, 14.7 % of the children had a Paediatric Trauma Score (P.T.S.) < or = 8 (n = 388). 3.8 % were considered severe multiple trauma patients, presenting an Injury Severity Score (I.S.S.) > or = 15 (n = 101). 4.2 % of the children required intensive care. The most frequent lesions were those of the locomotor system (58.1 %) and head injuries (34.9 %). Some type of surgical or orthopaedic procedure was performed under general anaesthesia in 1522 patients (57.8 %). The mean length of stay was 4.4 days (range 1 - 214 days). Sequelae of some form were detected in 36.4 % of the patients over 3 years of age. The total mortality was 0.5 % (n = 13), being 12.8 % in the group of patients with an I.S.S. > or = 15. CONCLUSIONS: Analysis of the data in our Registry has helped us to define the characteristics of the paediatric trauma population in our setting, to monitor the management of trauma in the different care levels and to develop prevention programmes. It has also enabled us to compare the results with those of other centres in terms of morbidity and mortality with the aim of identifying and correcting any possible deficiencies in the care system.

[Spinal cord and vertebral column injuries in children]. / Lesiones raquimedulares en la infancia.

AIMS: Analysis of main factors of spinal cord and vertebral column injuries in our environment. METHODS: We reviewed the data collected from the patients (n = 2640) admitted to our hospital because of trauma and included in our Registry from January 1995 to April 2002. Among this group, 86 patients (3.3%) had spinal cord and vertebral column injuries and were included in the study. RESULTS: Group gender distribution was 45 males and 41 females. In our group, 71 patients suffered vertebral fractures, 3 of them with spinal cord injuries (4.2%), 13 patients with vertebral subluxation, 11 of them between C1-C2, and 2 patients with spinal cord injury without radiographic abnormality. Only 71 patients, 4.9% of the total of the patients who were admitted with any type of fracture (n=1457), suffered vertebral fractures. These patients suffered 130 vertebral fractures, 35 of them (49.3%) suffered multiple fractures. Thoracic vertebrae were the most frequently affected (n=82, 63%). The most frequent localization was T4 toT8 (n=50, 38.5% and T11 to L2 (n=41, 31.5%). Age ranged between 12 and 15 years (n=35, 49.3%), with only 5 patients under 6 years. 90.9% of the patients with lumbar fractures were older than 8 years and 76.9% of the patients with cervical fractures were over 8 years. Motor vehicle accident was the most common cause in our series (n=20, 23.3%). 81% of these patients did not use safety belt. Ten children with cervical injuries were seen by medical staff at the prehospital stage, and only 4 of them arrived to Hospital with cervical collar. There were thirty five patients with thoracic or lumbar injuries but only 27 of them were transferred to our Institution by ambulance. Surgery was required in 2 patients, both of them with unstable fractures. Mean hospital stay was 17,1 days (range 2-37 days). CONCLUSIONS: Group gender distribution is similar between males and females and the incidence in our series is higher than other series of the literature. Thoracic injuries are the most frequent. It is necessary to improve prehospital management of these patients and to increase the use of safety belt. Spine injury incidence increased with age.

First appearance, distribution, and origin of macrophages in the early development of the avian central nervous system.

A phagocytic cell system of hemopoietic origin exists in the early avian embryo (Cuadros, Coltey, Nieto, and Martin: Development 115:157-168, '92). In this study we investigated the presence of cells belonging to this system in the central nervous system (CNS) of chick and quail embryos by using both histochemical staining for acid phosphatase and immunolabelling with antibodies recognizing cells of quail hemangioblastic lineage. The origin of these cells was traced in interspecific chick-quail yolk sac chimeras. Hemopoietic cells were detected within the CNS from developmental stage HH15 on, and steadily increased in number at subsequent stages. Analysis of yolk sac chimeras revealed that most of these cells were of yolk sac origin, although some hemopoietic cells of intramebryonic origin were also found in the CNS. Immunocytochemical, histochemical, and ultrastructural characterization allowed us to identify hemopoietic cells in the CNS as macrophages. These cells were consistently found in the brain vesicles and spinal cord, appearing (1) between undifferentiated neuroepithelial cells at dorsal levels of the CNS; (2) in areas of cell death; (3) in the marginal layer in close relationship with developing axons; (4) in large extracellular spaces in the subventricular layer; (5) on vascular buds growing through the marginal and subventricular layers; and (6) in the ventricular lumen. Macrophages in different locations varied in morphology and ultrastructure, suggesting that in addition to their involvement in phagocytosis, they play a role in other processes in the developing CNS, such as axonal growth and vascular development. The first macrophages migrate to the CNS independently of its vascularization, apparently traversing the pial basal lamina to reach the nervous parenchyma. Other macrophages may enter the CNS together with vascular buds at subsequent stages during CNS vascularization.

Development of microglia in the quail optic tectum.

The development of microglia in the quail optic tectum from embryonic day 6 to adulthood was studied by using the QH1 monoclonal antibody. In youngest tecta, microglial cells were scarcely present, but their number rose in subsequent stages. A clear pattern of microglial cell distribution was observable in embryos of 9-16 days. (1) Round cells appeared close to the ventricular layer. (2) Large numbers of ameboid and round labeled cells were seen in the stratum album centrale during development. A gradient of cell density was observable in this layer, as fewer labeled cells appeared in medial regions of the tectum than in lateral regions. (3) Maturing ramified cells were found in layers external to the stratum album centrale, where they increased in number and in branching complexity during development. In adult tecta, almost all microglial cells were of the mature ramified type and were distributed homogeneously in the different tectal layers, although in some layers they had particular morphological features. The distribution of microglia in the developing tectum and in adjacent regions provided insight into the routes of microglial cell invasion of the tectum during development. Apparently, a proportion of microglial cells reached the tectal parenchyma from the meninges and from the ventricular lumen, but the majority of them migrated along nerve fiber tracts from their entry point at the pial surface of the ventromedial caudal tectum. After they reached the stratum album centrale, microglial cells continued their migration toward more external layers, where they differentiated into ramified microglia.

Cell death in suboptic necrotic centers of chick embryo diencephalon and their topographic relationship with the earliest optic fiber fascicles.

The structural features of suboptic necrotic centers (SONCs) in the floor of the chick embryo diencephalon were studied. These necrotic areas were observed lateral to the prospective zone of the optic chiasm through developmental stages 14 to 24. The relationship between SONCs and the earliest optic fiber fascicles also was studied in an attempt to determine the possible significance of these cell death areas in the mechanism of optic pathway development. In SONCs, healthy neuroepithelial cells contain primary lysosomes and phagocytose fragments of dead cells. Discrete regions within the cytoplasm of some cells show electron-transparent vacuoles in contact with dense contents of ruptured lytic bodies. The cytoplasm of dying cells and dead cell fragments are notably electron dense, with numerous secondary lysosomes and electron-transparent vacuoles. These observations are interpreted on the assumption that after autophagic processes, condensation and fragmentation take place in dying cells of the SONCs. In the ventricular lumen adjacent to the SONCs, numerous more or less spherical bodies are observed that appear to be shed from the tip of the cells constituting the SONCs. Three different types of intraventricular bodies can be distinguished: loose, moderately dense, and highly dense. The first type appears to originate from apical portions of cells that undergo autolytic processes. Moderately dense fragments are interpreted as originating from dying cells in which the cytoplasm is undergoing condensation. Finally, highly dense intraventricular bodies appear to be fragments of dead cells that are shed into the ventricular lumen. SONCs separate the prospective area of the optic chiasm from lateral regions of the diencephalic floor. Extracellular spaces are poorly developed within the wall of the SONCs, whereas the neuroepithelium of the presumptive optic chiasm and regions located rostral and caudal to SONCs show abundant and extensive extracellular spaces. These are bounded by long marginal processes of neuroepithelial cells. Sagittal sections of embryonic heads at stages 22-24 reveal optic fiber fascicles penetrating the SONCs asymmetrically, as they are found only in its caudal half. These observations suggest that the SONCs function as doorways made of compact neuroepithelium, to be traversed by the earliest optic fibers before they reach the middle zone of the floor of the diencephalon through which they travel to the contralateral optic tract within large extracellular spaces.

Microglia in the avian retina: immunocytochemical demonstration in the adult quail.

Immunocytochemical techniques were used in conjunction with the QH1 antibody to study the morphological characteristics and distribution of microglia in the avascular retina of an avian species (the quail). The majority of microglial cells appeared in the outer and inner plexiform layers throughout the entire retina, whereas a few microglial cells in the nerve fiber layer were seen only in the central zone of the retina, near the optic nerve head. In the outer plexiform layer, microglial cells were star-shaped, with processes that ramified profusely in the horizontal plane. Fine process tips extended outward radially, insinuating themselves among the photoreceptors. A regular mosaic-like arrangement of microglial cells was evident in the outer plexiform layer, with no overlapping between adjacent cell territories. Microglial cells in the inner plexiform layer ramified through the entire width of this layer, showing radial and horizontal processes. Microglia in the inner plexiform layer also tended to be regularly distributed in a mosaic-like fashion, although there was slight overlapping between adjacent cell territories. Microglia density in this layer was approximately twice that in the outer plexiform layer. This pattern of microglial distribution was similar to that described in vascular retinae of several species of mammals, a finding that suggest that blood vessels are not responsible for the final locations of microglia in the adult retina, and that microglial precursors must migrate through long distances before they reach their precise destination.

Response of macrophage/microglial cells to experimental neuronal degeneration in the avian isthmo-optic nucleus during development.

Blockade of the retrograde axonal transport of isthmo-optic nucleus (ION) neurons in the avian embryo results in their massive degeneration. We used this system to investigate the response of macrophage/microglial cells to neuronal degeneration in the embryonic brain. Colchicine was injected into the right eye of quail or chick embryos at a time when the survival of ION neurons depends on retrograde trophic support from the retina, and the chronology of the subsequent macrophage/microglial response in the ION was analyzed. This response was restricted to the ION contralateral to the injected eye; no modifications of the normal state were observed in the surrounding parenchyma or in the opposite ION, used as control. The response was first detected 18 hours after the colchicine injection (18 hours pi), when an increase of the macrophage/microglial cell number was evident. The number of these cells in the affected ION increased, peaking at 40-48 hours pi. At later survival times, macrophage/microglial cells were progressively less abundant in the affected ION, which gradually diminished in size. At 120 hours pi the only remnant of the ION was a small cluster of macrophage/microglial cells, surrounded by a clear area with scarce nonmicroglial cells, in the region formerly occupied by the ION. This study reveals that a strong macrophage/microglial response occurs in the embryonic brain in response to neuronal degeneration but that these cells do not trigger the neuronal death, as they only appear after pyknotic fragments are already observable.