Endoscopic ultrasound-guided radiation therapy in pancreatic cancer.

During the last two decades, endoscopic ultrasound has revolutionized the diagnosis and treatment of gastrointestinal (GI) malignancies. The role of EUS has expanded well beyond its role as a diagnostic modality, and has emerged as a highly sophisticated interventional modality. More recently, EUS has paved its way into radiation oncology by either facilitating highly targeted image guided radiotherapy (IGRT) by insertion of fiducial markers in tumors or by direct instillation of radioactive seeds (brachytherapy). Although the experience regarding these techniques is in a preliminary stage, if developed further, this can potentially provide a highly accurate and minimally invasive approach for implantation of fiducial and radioactive seeds. This review will discuss potential role of EUS in implantation therapy, current literature and also speculate on future prospects for these EUS-guided interventions in pancreatic cancer.

Endoscopic ultrasound-guided fiducial markers and brachytherapy.

Endoscopic ultrasound (EUS)-guided needle placement of small radiopaque particles paves the way for EUS-guided fiducial markers and brachytherapy. Stereotactic body radiation therapy relies on image-guided radiation therapy (IGRT), permitting escalation of radiation dose to tumors while minimizing dose to normal tissues. Fiducial markers are radiopaque spheres, coils, or seeds that are implanted in or near tumors for IGRT. Brachytherapy is a therapeutic modality for various cancers. Both require precise and minimally-invasive seed placement, which EUS provides. This article reviews recent literature regarding the safety and efficacy of these procedures and discusses novel concepts, including EUS-guided celiac ganglia radiation neurolysis.

Strict perpendicular orientation of neural crest-derived neurons in vitro is dependent on an extracellular gradient of voltage.

We report extraordinary perpendicular orientations of neurons dependent on the presence of an external direct current (DC) voltage gradient. We chose chick dorsal root and postganglionic sympathetic neurons to evaluate. These were cultured in observation chambers in which the cells were separated from electrode products or substrate effects and maintained at 35°C. Both types of neurons showed a rapid restructuring of their anatomy. Typically, neurites that were not perpendicular to the voltage gradient were quickly resorbed into the cell body within a few minutes. Over 3-6 hr, significant new neurite growth occurred and was patterned perpendicular to the DC electrical field (Ef). This preferred asymmetry was dependent on the Ef, as was the initial retrograde degeneration of fibers. At 400-500 mV/mm, over 90% of the cells in culture assumed this orientation. Removal of the DC Ef led to a loss of the preferred orientation, with further random growth within the chambers. This is the first report of such responses in dorsal root ganglion neurons. We also used sympathetic neurons as a meaningful comparison to analyze whether there were any qualitative or quantitative differences between these two cell types of neural crest origin. We discuss the means by which these orientations were achieved.

Evaluation of endoscopic-ultrasound-guided celiac ganglion irradiation with iodine-125 seeds: a pilot study in a porcine model.

BACKGROUND AND STUDY AIMS: Implantation of iodine-125 ( (125)I) seeds under the guidance of endoscopic ultrasonography (EUS) has been proved to be a safe alternative treatment option for advanced pancreatic cancer. The main purpose of this study was to evaluate the feasibility and safety of EUS-guided radiation of the celiac ganglia with (125)I seeds in a porcine model. METHODS: Twelve domestic pigs were randomly divided into three groups. The pigs in group A had blank seeds implanted, and groups B and C had 0.4 mCi and 0.8 mCi (125)I seeds implanted, respectively. Enhanced CT scan and 3-D vascular remodeling were used to check the location of the seeds. All animals were killed and celiac ganglia were checked at 14 and at 60 days after procedure. Necrosis and apoptosis in celiac ganglia and adjacent vessels and organs were also observed. RESULTS: EUS-guided implantations of (125)I seeds in celiac plexus were successful at first procedure in 10 animals. The remaining two animals were implanted successfully the next day. No severe complications occurred in any animal and no damage was found in the surrounding organs. At day 60 after operation, the apoptotic index in the ganglia was 0.53 in the 0.4 mCi group and 0.94 in the 0.8 mCi group. No apoptotic cells were found in the control group implanted with blank seeds. Damage to vessels and surrounding organs by radioactive seeds was observed in only one pig at each time point. CONCLUSION: EUS-guided implantation of (125)I seeds beside the celiac ganglia is a safe procedure and can induce apoptosis of local neurons. This new method may lead to an alternative treatment for pain accompanying pancreatic diseases in human.

[Effects of linear polarized light irradiation around the lumbar sympathetic ganglion area upon the skin temperature of lower extremities].

BACKGROUND: The effect of linear polarized light irradiation around the lumbar sympathetic ganglion area upon the skin temperature of legs may be similar to that of irradiation of near stellate ganglion area upon arms. METHODS: Linear polarized light irradiation was induced with SUPER LIZER (Tokyo Iken, Tokyo, Japan). The C probe of SUPER LIZER was placed on the left side of the supine at the level of L2. RESULTS: Seven-minute irradiation around the lumbar sympathetic ganglion area increased significantly the skin temperature of the irradiated side leg. CONCLUSIONS: These results suggest that linear polarized light irradiation around the lumbar sympathetic ganglion area might be useful and beneficial for clinical application.

Effect of He-Ne laser irradiation on synaptic transmission of the superior cervical sympathetic ganglion in the rat.

The effect of low-power He-Ne laser on synaptic transmission was studied in the superior cervical sympathetic ganglion of Wistar rats. Extracellular and intracellular recordings were made from isolated ganglia before and after laser irradiation. In addition, effects of ganglion irradiation on skin blood flow were observed in in vivo preparations. Irradiation on the isolated ganglion decreased the amplitude of evoked compound action potentials in the extracellular recordings. Intracellular recordings from ganglion cells revealed that the neuronal membrane was hyperpolarized, while threshold potential and latency of response were unchanged. The reduction of skin blood flow during preganglionic nerve stimulation lessened by irradiation on the ganglion. Our results indicate that low-power He-Ne laser depresses sympathetic ganglionic transmission, and hyperpolarization of ganglionic cells takes part in the mechanism of action.

Bilateral irradiation of head and neck induces an enhanced expression of substance P in the parasympathetic innervation of the submandibular gland.

Substance P and calcitonin gene-related peptide (CGRP) are present in nerve fibers innervating the submandibular gland. Radiotherapy of tumors in the head and neck region usually embraces the salivary glands in the irradiated field and consequently a dramatic decrease in salivary function is seen. In this study, the submandibular glands and ganglia of rats subjected to fractionated irradiation were examined by use of immunohistochemical techniques for demonstration of substance P and CGRP. Irradiation was given on five consecutive days (daily doses of 6-9 Gray) with unilateral or bilateral irradiation techniques. Specimens of control and experimental animals were processed in parallel. A marked increase in the expression of substance P in the ganglionic cells--presumably parasympathetic--and in the number of fibers showing substance P-like immunoreactivity in association with acini and small ducts was seen in response to bilateral irradiation. (Surprisingly, unilateral irradiation of the parotid area had no effect on peptide distribution in the irradiated gland and ganglion). No changes in the pattern of CGRP immunoreactivity occurred. In the trigeminal ganglion, which supplies the submandibular gland with the majority of the sensory substance P- and CGRP-containing nerve fibers, no changes in the expression of substance P or CGRP immunoreactivity were seen. The results suggest that bilateral irradiation leads to an increase in the synthesis of substance P-like substance in the parasympathetic ganglionic cells supplying the submandibular gland with secretory nerves, and can thus be an additional factor in explaining the altered secretory capacity of salivary glands.

Ultraviolet light activates blocking actions of dantrolene on intracellular Ca2+ release in bullfrog sympathetic neurones.

Effects of dantrolene, a blocker of intracellular Ca2+ release, on the oscillation of the intracellular Ca2+ ([Ca2+]i) induced by caffeine were studied in bullfrog sympathetic ganglion cells, using a Fura-2 fluorescence technique. Dantrolene blocked the Ca2+ oscillation only in the cell illuminated by ultraviolet light (335-385 nm). Likewise, the blocking effects on rhythmic Ca(2+)-dependent hyperpolarizations, representing Ca2+ oscillations via activation of Ca(2+)-dependent K+ channel, occurred only under the illumination with ultraviolet light (335-385 nm), but not with visible light (404-417 nm). This wavelength dependence differs from the absorbance spectrum of dantrolene. On the other hand, dantrolene preirradiated with ultraviolet light under dark condition or ultraviolet light itself did not affect the [Ca2+]i oscillation. The blocking action was not prevented by the pretreatment of the cells with reducing agents. These results indicate that illumination of the Ca2+ release channel or dantrolene itself with ultraviolet light (possibly the former) is necessary for the drug to exert its blocking effect. Furthermore, dantrolene was found to decrease Fura-2 fluorescence and to increase cell autofluorescence, leading sometimes to a false decrease in the basal [Ca2+]i.

[The direct action of high doses of gamma quanta and neutrons of different energies on the sympathetic ganglion neurons in the frog]. / Neposvredstvennoe deistvie vysokikh doz gamma-kvantov i neitronov raznoi énergii na neirony simpaticheskogo gangliia liagushki.

Irradiation of isolated frog sympathetic ganglia IX-X with high doses caused a long-term depolarization of a single ganglion cell and increase of synaptic activation threshold. The radiation effects observed were not accompanied by the transmission failure. The authors suggest that the changes in the synaptic mechanisms play a minor role in the development of the CNS syndrome.

[Energy metabolism in structures of the visual analyzer and neurons of the sympathetic ganglion after irradiation of the eye with low-intensity infrared laser radiation in the near-spectrum region]. / Sostoianie énergeticheskogo obmena v strukturakh zritel'nogo analizatora i neironakh simpaticheskogo gangliia posle oblucheniia glaza nizkointensivnym infrakrasnym lazernym izlucheniem blizhnei oblasti spektra.

After irradiation of one eye by low-intensive infrared laser with near spectral region within 5 and 20 min an increase in aerobic oxidation (activation of glutamate- and succinate dehydrogenases, decrease in activity of lactate dehydrogenase and in content of lactate) as well as alterations in the antioxidant activity were observed in structures of both eyes (irradiated and untreated), in visual cortex of both hemispheres and in neurocytes of upper cervical sympathetic ganglions. These results suggest that generalized metabolic reactions are developed in a body in response to laser irradiation. Mechanism of these reactions appears to involve not only the neuro-reflex pathways but it related also to the direct effect of the radiation on structures of eye and brain. The low-intensive laser radiation penetrated into brain through eye retrobulbar tissues and bones.

[Effect of laser radiation on the posttraumatic recovery of the interneuronal connections in the sympathetic trunk]. / Vliianie lazernogo izlucheniia na posttravmaticheskoe vosstanovlenie mezhneironnykh sviazei simpaticheskogo stvola.

Low energetic laser radiation produces stimulating influence on posttraumatic regeneration of interneuronal connections of the sympathetic trunk. Local effect of the low energetic laser with exposition of 25 sec., power of the incident ray 16 mVt/cm2 increases the cause of reparative regeneration of sympathetic preganglionic fibers. Restoration of the cranial cervical ganglion (CCG) connections with the spinal cord takes place 5-6 days earlier comparing with the control. Localization and structural organization of the spinal initial neurons is stated, their processes reach the CCG.