Optical coherence tomography for bladder cancer -- ready as a surrogate for optical biopsy? Results of a prospective mono-centre study.

INTRODUCTION: New modalities like Optical Coherence Tomography (OCT) allow non-invasive examination of the internal structure of biological tissue in vivo. The potential benefits and limitations of this new technology for the detection and evaluation of bladder cancer were examined in this study. MATERIALS AND METHODS: Between January 2007 and January 2008, 52 patients who underwent transurethral bladder biopsy or TUR-BT for surveillance or due to initial suspicion of urothelial carcinoma of the bladder were enrolled in this study. In total, 166 lesions were suspicious for malignancy according to standard white light cystoscopy. All suspicious lesions were scanned and interpreted during perioperative cystoscopy using OCT. Cold cup biopsies and/or TUR-B was performed for all these lesions. For this study we used an OCT-device (Niris, Imalux, Cleveland, US), that utilizes near-infrared light guided through a flexible fibre-based applicator, which is placed into the bladder via the working channel of the cystoscope. The technology provides high spatial resolution on the order of about 10-20 microm, and a visualization of tissue to a depth of about 2 mm across a lateral span of about 2 mm in width. The device used received market clearance from the FDA and CE approval in Germany. The diagnostic and surgical procedure was videotaped and analyzed afterwards for definitive matching of scanned and biopsied lesion. The primary aim of this study was to determine the level of correlation between OCT interpretation and final histological result. RESULTS: Of 166 scanned OCT images, 102 lesions (61.4%) matched to the same site where the biopsy/TUR-BT was taken according to videoanalysis. Only these video-verified lesions were used for further analysis. Of all analyzed lesions 88 were benign (inflammation, edema, hyperplasia etc.) and 14 were malignant (CIS, Ta, T1, T2) as shown by final histo?pathology. - All 14 malignant lesions were detected correctly by OCT. Furthermore all invasive tumors were staged correctly by OCT regarding tumor growth beyond the lamina propria. There were no false negative lesions detected by OCT. Sensitivity of OCT for detecting the presence of a malignant lesion was 100% and sensitivity for detection of tumor growth beyond the lamina propria was 100% as well. Specificity of OCT for presence of malignancy was 65%, due to the fact that a number of lesions were interpreted as false positive by OCT. CONCLUSION: As a minimally invasive technique, OCT proved to have extremely high sensitivity for detection of malignant lesions as well as estimation of whether a tumor has invaded beyond the lamina propria. However, specificity of OCT within the bladder was impaired (65%), possibly due to a learning curve and/or the relatively low spatial resolution and visualization depth of the OCT technology. Further studies and technical development are needed to establish an adequate surrogate for optical biopsy.

Characteristics of midbrain control of spinal nociceptive neurons and nonsomatosensory parameters in the pentobarbital-anesthetized rat.

1. GABAergic mechanisms in the midbrain periaqueductal gray (PAG) have been proposed to control the activity of descending antinociceptive systems and defensive behavior. Here, the effect of neuronal disinhibition by gamma-aminobutyric acid (GABAA) receptor blockade at midbrain sites on spinal neuronal responses to noxious and innocuous skin stimulation was quantitatively characterized. It was compared with the effect of direct neuronal excitation by glutamate microinjections or electrical stimulation at identical sites. Changes in mean arterial blood pressure and other nonsomatosensory responses were also assessed. 2. Responses of 101 multireceptive lumbar spinal dorsal horn neurons to noxious radiant skin heating (50 degrees C, 10 s), innocuous skin brushing, and electrical stimulation of primary afferent A- and C-fibers were recorded in deeply pentobarbital-anesthetized rats. The mean blood pressure was continuously monitored in one carotid artery, and other nonsomatosensory parameters, such as frequency and depth of spontaneous respiration and contractions of abdominal and facial muscles, were classified according to their relative intensity into five groups. 3. A fine, multibarrel glass pipette was constructed for monopolar electrical stimulation and microinjection of the GABAA receptor antagonist bicuculline (40, 200, or 400 pmol), or glutamate (10-50 nmol), or Fast Green dye in 50 or 100 nl at identical sites in the midbrain. 4. Bicuculline microinjections into discrete regions of the PAG selectively abolished spinal neuronal responses to noxious skin stimulation but did not affect brush-evoked responses or responses to electrical A-fiber stimuli. This antinociception was often, albeit not necessarily, accompanied by tachypnoea and abdominal and facial muscle contractions and changes--mostly increases--in mean arterial blood pressure. Injections into other areas of the PAG and adjoining ventral tegmentum (VT) were less effective. The vast majority of injection sites in the lateral tegmentum (LT) were ineffective. 5. Glutamate microinjections at midbrain sites to detect areas of origin of descending antinociceptive neurons were characterized by a high incidence (greater than 50%) of false-negative results, as bicuculline was shown to be effective at numerous glutamate-insensitive sites. Glutamate microinjections into some sites of the PAG and adjoining VT reduced, but did not abolish, spinal neuronal responses to noxious skin heating. Injections into the LT were ineffective. 6. The efficacy of electrical stimulation at midbrain sites on spinal nociceptive responses had no predictive value for the effect of glutamate or bicuculline.(ABSTRACT TRUNCATED AT 400 WORDS)

Blockade of GABAA receptors in the midbrain periaqueductal gray abolishes nociceptive spinal dorsal horn neuronal activity.

Single spinal dorsal horn neuronal responses to noxious skin heating or innocuous skin brushing were recorded in pentobarbital anesthetized rats. The heat-evoked activity was selectively abolished by blockade of GABAA receptors in the midbrain periaqueductal grey (PAG) by microinjections of 40 or 400 pmol bicuculline. It is concluded that antinociceptive output neurons in the PAG that trigger descending inhibition are maximally active when released from tonic GABAergic inhibition.