RESUMEN
INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. TRIAL DESIGN: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Laparoscopía , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Selección de Paciente , Proyectos de InvestigaciónRESUMEN
Modulation of responses of four types of ascending tract cells by noradrenaline and serotonin was compared in order to investigate how information forwarded by these cells may be gated by monoaminergic tract neurons. Spinocervical tract, postsynaptic dorsal column and dorsal spinocerebellar tract neurons located in Clarke's column and in the dorsal horn were identified by their axonal projections. Noradrenaline and serotonin were applied ionophoretically close to a selected neuron, and their effects were tested on extracellularly recorded responses of this neuron to electrical stimulation of low-threshold skin afferents and group II muscle spindle afferents. The modulatory actions of noradrenaline and serotonin were estimated from changes in the number of responses evoked by 30 successive stimuli, the minimal latencies of these responses, and their firing frequency. All four populations of ascending tract neurons investigated were modulated by serotonin and noradrenaline, but not in the same way. The responses were most often depressed by noradrenaline and facilitated by serotonin, but in some types of neuron they were affected in the same direction. Transmission from low-threshold skin and group II muscle afferents changed in the same direction in some types of neuron but in the opposite direction in other types. The results indicate that transfer of information from skin and group II muscle afferents to supraspinal centres may be gated by descending monoaminergic pathways in a highly differentiated manner, and is adjusted to the requirements of various behavioural situations.
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Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/fisiología , Norepinefrina/farmacología , Serotonina/farmacología , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiología , Animales , Gatos , Cerebelo/citología , Cerebelo/fisiología , Cuello , Médula Espinal/citología , Sinapsis/fisiologíaRESUMEN
Effects of ionophoretic application of serotonin and of one of its agonists were tested on responses of dorsal horn dorsal spinocerebellar tract neurons evoked by electrical stimulation of peripheral nerves. Both drugs depressed monosynaptically evoked actions of group II muscle afferents; they decreased the number and/or increased the latency of spike potentials evoked by these afferents. In contrast, synaptic actions of low-threshold cutaneous afferents (mono- or oligosynaptic) were facilitated in the majority of the neurons, as judged by decrease in the latency of spike potentials evoked by stimulation of a cutaneous nerve and/or an increase in the number of these potentials. It is proposed that facilitatory actions assist in maintaining tonic discharges of dorsal spinocerebellar tract neurons in some movements and that the selective control of group II input is used to correlate activity of spinal and supraspinal neurons. Both actions may be subserved by tight contacts between serotoninergic nerve fibres and dorsal spinocerebellar tract neurons, which have been revealed in a parallel study.
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Cerebelo/citología , Interneuronas/efectos de los fármacos , Serotonina/farmacología , Médula Espinal/citología , 8-Hidroxi-2-(di-n-propilamino)tetralin/administración & dosificación , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Gatos , Cerebelo/efectos de los fármacos , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Iontoforesis , Vías Nerviosas/citología , Vías Nerviosas/efectos de los fármacos , Neuronas Aferentes/fisiología , Nervios Periféricos/citología , Nervios Periféricos/efectos de los fármacos , Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/farmacología , Piel/inervación , Médula Espinal/efectos de los fármacos , Sinapsis/efectos de los fármacosRESUMEN
The effects of one 5-HT1A serotonin agonist (8-OH-DPAT) and of two alpha 2 noradrenaline agonists (tizanidine and B-HT 933) were tested on the transmission between group II muscle afferents and spinal neurons in the sacral segments of the spinal cord in the cat. These agonists have previously been found to depress transmission from group II muscle afferents either in the dorsal horn or in the intermediate zone of midlumbar segments, and this study addressed the question of whether their actions in the sacral segments are similarly selective. The drugs were applied ionophoretically and their effects were tested on field potentials evoked from group II muscle afferents. As judged by changes in the amplitude of the early components of these field potentials, the transmission is effectively depressed by the serotonin agonist (to 56 +/- 26% after 2 min of ionophoresis of 8-OH-DPAT) but not by the noradrenaline agonists (to 97 +/- 12% after 6 min of ionophoresis of B-HT 933 and to 95 +/- 17% after 6 min of ionophoresis of tizanidine). These data suggest that transmission from group II muscle spindle afferents in the sacral segments is under control of serotonin releasing neurons, as in the dorsal horn of midlumbar segments, but leave open the question of the similarities or differences in the mechanisms (pre- and/or postsynaptic) of this control.
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Monoaminas Biogénicas/farmacología , Músculo Esquelético/inervación , Neuronas Aferentes/efectos de los fármacos , Médula Espinal/fisiología , Transmisión Sináptica/efectos de los fármacos , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Agonistas de Receptores Adrenérgicos alfa 2 , Animales , Gatos , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Iontoforesis , Músculo Esquelético/efectos de los fármacos , Norepinefrina/agonistas , Norepinefrina/fisiología , Agonistas de Receptores de Serotonina/farmacología , Médula Espinal/citologíaRESUMEN
1. Ascending tract neurones located in the dorsal horn of sacral segments of the spinal cord have been investigated by extracellular and intracellular recording in the anaesthetized cat. The aim was to determine whether information from group II afferents that terminate within the sacral segments is conveyed to supraspinal structures and which types of neurones are involved. 2. A considerable proportion of ascending tract neurones found in the dorsal horn in the same segments as the pudendal (Onuf's) motor nucleus were excited by group II muscle afferents. The great majority (93%) of these neurones had axons ascending in ipsilateral funiculi. Spinocervical tract neurones constituted the largest proportion (82%) of such neurones, while very few spinocerebellar tract and propriospinal neurones and no postsynaptic dorsal column neurones were found among them. 3. In addition to activation by group II muscle afferents all of the neurones were strongly excited by cutaneous afferents. The most potent excitation was evoked by afferents of the posterior biceps-semitendinosus and gastrocnemius muscle nerves and by afferents of the cutaneous femoris, sural and pudendal nerves. The latencies of intracellularly recorded excitatory potentials were indicative of a high incidence of monosynaptic coupling between the afferents and ascending tract neurones. 4. The highly effective monosynaptic excitation of spinocervical tract neurones in the sacral segments by group II afferents is in contrast to the weak disynaptically mediated actions of group II afferents on such neurones in the L6-L7 segments but comparable to the actions of group II afferents on ascending tract neurones in the midlumbar segments. 5. Both the patterns of peripheral input and the latencies of synaptic actions in ascending tract neurones were similar to those in interneurones at the same locations (accompanying report). Similar information is therefore likely to be processed by both categories of neurones. 6. The role of sacral spinocervical tract neurones as a system for transmitting information from group II muscle afferents to supraspinal centres and the potential contribution of this system to the perception of limb position are discussed.
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Músculos/inervación , Neuronas Aferentes/fisiología , Neuronas/fisiología , Médula Espinal/fisiología , Vías Aferentes/fisiología , Animales , Gatos , Cerebelo/citología , Cerebelo/fisiología , Región Lumbosacra , Inhibición Neural , Piel/inervación , Médula Espinal/citología , Transmisión SinápticaRESUMEN
Peripheral input to spino-cervical tract (SCT) neurons located in the L4 and L5 segments of the cat spinal cord was investigated using both extracellular and intracellular recording. The main aim was to find out whether midlumbar SCT neurons are excited monosynaptically not only by cutaneous afferents but also by group II muscle afferents, as in the sacral segments but apparently not in the caudal lumbar segments. Input from group II muscle afferents was found in 73% of investigated neurons; the latencies of excitation by group II afferents were compatible with a monosynaptic coupling between these afferents and 62% of neurons. The majority of the midlumbar SCT neurons were excited by group II afferents of the quadriceps and deep peroneal nerves. The predominant monosynaptic input from cutaneous afferents to the same neurons was from the saphenous nerve.
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Músculo Esquelético/inervación , Neuronas Aferentes/fisiología , Médula Espinal/fisiología , Animales , Gatos , Estimulación Eléctrica , Miembro Posterior/inervación , Miembro Posterior/fisiología , Microelectrodos , Vías Nerviosas/fisiología , Piel/inervación , Médula Espinal/citologíaRESUMEN
The morphology of 12 sacral interneurones with peripheral input from group II muscle afferents was analyzed after intracellular injection of horseradish peroxidase (HRP). The neurones were located in Rexed's laminae III-V overlying the pudendal (Onuf's) motor nucleus. The interneurones had medium sized elongated somata and dendrites projecting radially. All of the interneurones were funicular neurones and fell into two categories depending on whether their axons ran within the dorsal part of the lateral funiculus (DLF; n = 7) or within the ventral funiculus, or the ventral part of the lateral funiculus (VF or VLF; n = 4). The latter were located more rostrally. Within the DLF similar proportions of stem axons and secondary axonal branches descended and ascended. Within the VF and VLF all of the axons ascended. Collaterals of axons running in the DLF arborized primarily within the dorsal horn and the intermediate zone; none were found to approach the motor nuclei. In contrast, collaterals of axons running in the VF/VLF arborized in both the intermediate zone and the ventral horn and passed close to the motor nuclei. We conclude that sacral interneurones with group II input are morphologically nonhomogenous and that only those located most rostrally might have direct actions upon motoneurones. Both the axonal projections and the input (from group II but not from group I muscle afferents and from skin afferents) of sacral interneurones indicate that they are homologous to dorsal horn group II interneurones in the midlumbar segments. They appear, however, to form part of more local neuronal networks than their midlumbar counterparts.