Hexaminolevulinate-induced fluorescence colonoscopy versus white light endoscopy for diagnosis of neoplastic lesions in the colon.

BACKGROUND AND STUDY AIMS: To compare the rate of detection of colorectal neoplastic lesions using the selective photosensitizer precursor hexaminolevulinate (HAL) combined with a new fluorescence video endoscope system against that of standard white light endoscopy, and secondarily, to evaluate the safety profile of HAL-induced fluorescence colonoscopy. PATIENTS AND METHODS: This prospective phase II clinical pilot study from two hospital study centers included 25 patients with known or highly suspected colorectal neoplasia. They underwent sensitization with locally applied 500 ml HAL enemas at a concentration of 1.6 mmol/L. At 60 minutes after enteral HAL administration, fluorescence imaging was done using a special light source capable of delivering either white light or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. RESULTS: Using histology as the gold standard, 55 / 93 of neoplastic lesions were detected with white light endoscopy, 53 / 93 with both white and blue light, 38 / 93 with blue light and second-pass white light, and 27/93 with blue light only. Of all neoplastic lesions, 91 / 93 revealed red fluorescence under fluorescence imaging ( P < 0.0001). Fluorescence mode showed 38.7 % (36 / 93) more neoplasms than did white light endoscopy. An isolated slight elevation of bilirubin, by a factor of 1.5, was noted after the administration of HAL. CONCLUSIONS: Administration of HAL as enema induces selective lesion fluorescence and increases lesion detection rate in patients with colorectal neoplasia, especially of flat, nonvisible adenomas.

Early detection of premalignant conditions in the colon by fluorescence endoscopy using local sensitization with hexaminolevulinate.

BACKGROUND AND STUDY AIMS: We aimed to determine the feasibility of obtaining selective fluorescence of precancerous/cancerous lesions in the colon with a new fluorescence video endoscope system in combination with the selective photosensitizer precursor hexaminolevulinate (HAL), and to carry out a dose-finding study with evaluation of the optimal dose and application time. PATIENTS AND METHODS: 12 patients with colorectal lesions underwent sensitization with locally applied HAL enemas in two concentrations (0.8 mmol and 1.6 mmol). The examination was conducted either 30 or 60 minutes after rectal administration of the sensitizer, using a special light source capable of delivering either white or blue excitation light. Red fluorescence induced by illumination with blue light was detected via a prototype fluorescence video colonoscope. Biopsies were taken from suspicious areas found with white or blue light. Corresponding endoscopic, fluorescence, and microscopic findings were compared. RESULTS: Using histological findings as the gold standard, 52/53 of the premalignant/malignant lesions showed red fluorescence under the photodynamic diagnosis (PDD) examination; 38/53 were detected with white-light endoscopy. The PDD mode showed 28 % more polyps than did white-light endoscopic imaging. The greatest fluorescence intensity in precancerous lesions was found with retention for 60 minutes of 500 ml of 1.6 mmol HAL. CONCLUSIONS: Administration of HAL enema induces selective lesion fluorescence and increases the lesion detection rate in patients with colorectal adenoma and early carcinoma.

Fluorescence induced with 5-aminolevulinic acid for the endoscopic detection and follow-up of esophageal lesions.

BACKGROUND: The aim of this study was to investigate the use of orally administered 5-aminolevulinic acid (ALA) for in vivo photodynamic diagnosis and follow-up of premalignant and malignant esophageal lesions. METHODS: Twenty-two patients with known or treated malignant and precancerous esophageal lesions were sensitized with orally administered ALA (15 mg/kg). Six patients had Barrett's esophagus, with or without severe dysplasia, 5 squamous cell cancer or early-stage (uT1N0M0) adenocarcinoma, 1 advanced-stage (uT3N1) adenocarcinoma, and 1 patient a lesion with an appearance that suggested esophageal cancer. Nine patients underwent photodynamic diagnosis for follow-up after treatment of esophageal cancer with curative intent; 6 had no macroscopically visible lesion and 3 a barely visible lesion under standard (white-light) endoscopy. Photodynamic diagnosis was conducted 6 to 7 hours after oral administration of ALA by using a special light source capable of delivering either white or violet-blue light. Red fluorescence was detected with a charged coupled device camera attached to a fiberoptic endoscope. Corresponding endoscopic, fluorescence, and microscopic findings were compared. RESULTS: By using histology as the reference standard (n = 86 biopsies), 85% of the biopsy sites with premalignant or malignant histopathology exhibited red fluorescence, whereas only 25% were detected with white-light endoscopy. CONCLUSION: ALA-induced fluorescence might be useful for the early endoscopic detection of malignant esophageal lesions and follow-up after treatment of such lesions with curative intent.

Endoscopic fluorescence spectroscopy in the upper GI tract for the detection of GI cancer: initial experience.

OBJECTIVE: The aim of this study was to investigate autofluorescence spectroscopy using violet-blue excitation light for the in vivo diagnosis of GI cancer during routine endoscopy. METHODS: Fluorescence spectra were obtained from normal mucosa and cancerous lesions of the esophagus and stomach. The spectroscopic system used comprised a special light source capable of delivering either white or violet-blue light to induce autofluorescence of tissue via the endoscope. Endogenous fluorescence spectra emitted by the tissue were recorded with a fiberoptic probe and analyzed with a spectrographic detector system consisting of a polychromator with a photodiode array and an optical multichannel analyzer. The data of each spectrum were sampled within the range of 450-700 nm and stored in a personal computer. RESULTS: Esophageal squamous cell cancer, adenocarcinoma of the esophagus, and adenocarcinoma of the stomach show specific differences in the emitted fluorescence spectra compared with normal mucosa. CONCLUSIONS: Light-induced fluorescence spectroscopy might be a useful tool for the endoscopic in vivo detection of dysplasia and early carcinoma in the upper GI tract. Further trials are needed to test the validity of this new optical detection system.

Light-induced autofluorescence spectroscopy for the endoscopic detection of esophageal cancer.

BACKGROUND: Any innovative optical system that facilitates the early endoscopic detection of neoplastic change in the GI mucosa has the potential to greatly improve survival and quality of life for patients prone to have GI malignancies develop. The present article describes light-induced autofluorescence spectroscopy with violet-blue excitation light for in vivo diagnosis of cancerous tissue of the esophagus during routine endoscopy. METHODS: One hundred twenty-nine endogenous fluorescence spectra were obtained from normal mucosa and malignant lesions in 9 patients with squamous cell cancer and 4 with adenocarcinoma of the esophagus. Following spectrographic measurements, biopsy specimens were obtained for definitive classification of the spectra. A special light source capable of delivering either white or violet-blue light for excitation of tissue autofluorescence by means of an endoscope was used. Endogenous fluorescence spectra emitted by tissues were detected with a fiberoptic probe and analyzed with a spectrograph. RESULTS: Squamous cell cancer and adenocarcinoma of the esophagus exhibit specific changes in the emitted fluorescence spectra as compared with normal mucosa. Based on the results obtained in earlier studies, malignant and benign spectra were differentiated with the aid of a mathematical algorithm. By using this algorithm, a sensitivity of 97% and specificity of 95% were obtained for the diagnosis of esophageal carcinoma. CONCLUSIONS: Light-induced fluorescence spectroscopy is useful for the endoscopic detection of squamous cell cancer and adenocarcinoma of the esophagus. This spectroscopic study provides a basis for the design of a simplified autofluorescence imaging system for detection of esophageal neoplasms.

Light-induced autofluorescence spectroscopy for tissue diagnosis of GI lesions.

BACKGROUND: The present article describes light-induced autofluorescence spectroscopy using violet-blue excitation light for endoscopic in vivo measurements in the upper GI tract. The spectra of normal mucosa, cancer, and dysplastic lesions of the esophagus and stomach are presented and compared. METHODS: Over 120 spectra were obtained in 11 patients of normal mucosa and malignant lesions in the esophagus and stomach during routine endoscopy. A special light source capable of delivering either white or violet-blue light was used for the excitation of tissue auto-fluorescence via the endoscope. Endogenous fluorescence spectra emitted by the tissue were collected with a fiberoptic probe and analyzed with a spectrograph. After spectrographic measurements biopsies were taken for definitive classification of histopathologic status. RESULTS: As compared with normal mucosa, (pre) cancerous lesions were associated with special changes in the emitted fluorescence spectra. The spectrographic records were influenced by the intensity of the illumination and on the position of the probe (distance and angle). CONCLUSION: Fluorescence spectroscopy with a slightly modified conventional light source might be useful for the endoscopic detection of dysplasia and early-stage carcinoma in the upper GI tract. Prospective trials need to determine the sensitivity and specificity of this new method.

[Isolated ACTH deficiency as a rare cause of recurrent syncope and hypoglycemia]. / Isolierter ACTH-Mangel als seltene Ursache rezidivierender Synkopen und Hypoglykämien.

HISTORY AND CLINICAL FINDINGS: A 63-year-old man was assigned into emergency room presenting with an acute syncope associated with hypoglycemia and hypotension. Clinical findings showed a pale, waxing-colored skin and a disorder of impulse. During the clinical stay the patient's behavior was slowed down and adynamic. INVESTIGATIONS: After exclusion of cardiovascular and neurologic disorders as reason for the repeated syncopes a detailed endocrine diagnostic screening was performed, which revealed a deficiency of cortisol with missing increase of cortisol in the ACTH stimulation test. The ACTH-GnRH-TRH test showed an isolated deficiency of corticotropic hormones. Stimulation with CRH revealed no increase of ACTH or cortisol. Insulin tolerance test revealed an isolated ACTH insufficiency with consecutive deficit of cortisol. A tumor of the adrenal gland was excluded by abdominal scan. Cerebral CT was inconspicuous. Cerebral NMR was suspicious of volume deficiency of the hypophysis. TREATMENT AND COURSE: Under therapy with hydrocortisone 20 mg and fludrocortisone 0.05 mg orally the clinical symptoms of the patient improved impressively. The patient became efficient and dynamic. Systolic blood pressure increased in mean over 120 mm Hg. There were no more hypoglycemic episodes. CONCLUSION: Secondary insufficiency of the adrenal gland should be considered as a rare cause of hypoglycemia if combined with hypotensive circulatory disturbance and missing pigmentation of the skin.

Disposable-sheath, flexible gastroscope system versus standard gastroscopes: a prospective, randomized trial.

BACKGROUND: Endoscopically transmitted infections due to inadequate disinfection are rare but well-recognized complications. A new prototype of a flexible, fiberoptic endoscope has been developed that uses a disposable sheath to cover and protect all working surfaces of the endoscope from contamination. The present study investigated the function, reprocessing, and hygienic status of this endoscope system in comparison with standard systems. METHODS: In a prospective, randomized trial, 100 upper endoscopic procedures (50 standard, 50 sheathed) were performed. Analog rating scales were used to evaluate endoscopic performance and reprocessing. Reprocessing time, procedure duration, insertion depth, total instrument downtime, and problems occurring during the procedure were recorded. Microbiologic swabs were obtained from each endoscope. RESULTS: Mean procedure duration was slightly longer with the sheathed system than with standard endoscope (9.9 vs. 8.4 min). Set up and reprocessing times, however, were significantly shorter with the Endosheath (8.9 vs. 48.4 min with the standard endoscope). The disposable-sheath endoscope system permits the rate of performance of procedures to be increased by a factor of up to 3.0. Both endoscopists and reprocessing personnel preferred the standard endoscope. No post-procedure sheath leakage or rupture was seen. CONCLUSION: Our results suggest that the "disposable endoscope" may have important advantages in terms of decreased instrument turn-around time and potentially improved safety.

Endoscopic photodynamic diagnosis: oral aminolevulinic acid is a marker of GI cancer and dysplastic lesions.

BACKGROUND: Dysplasia and early cancer of the upper gastrointestinal (GI) tract often are undetected at white-light endoscopy. We describe oral administration of 5-aminolevulinic acid for the in vivo photodynamic diagnosis of premalignant and malignant lesions during endoscopy. METHODS: Four patients with known gastric adenoma (n = 1), macroscopically undetected but histologically proven esophageal squamous cell cancer (n = 1), suspected early cancer of the esophagus (n = 1), and multiple duodenal adenomas (n = 1) were sensitized with 5-aminolevulinic acid administered orally (15 mg/kg body weight). Photodynamic diagnosis was conducted after a retention time of 6 to 7 hours with a special light source capable of delivering either white or violet-blue light. Red fluorescence was detected through the gastroscope with an image-intensifying camera. RESULTS: All malignant lesions exhibited red or bluish fluorescence during photodynamic diagnosis. Fluorescence-negative mucosal areas proved to be histologically benign. CONCLUSION: Fluorescence induced with 5-aminolevulinic acid might be useful for the endoscopic detection of dysplasia and early carcinoma in the upper GI tract. Further investigations are needed to evaluate the sensitivity and specificity of photodynamic diagnosis for different tumor entities.

Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene.

After the story of success of hormone blockers for catecholamines, aldosterone and angiotensin II and their successful implementation into clinical practice another endocrine cardiovascular system has come into focus. It has long been known, that the hormone vasopressin plays an important role in peripheral vasoconstriction, hypertension and in several disease conditions with dilutional hyponatremia in edematous disorders, like congestive heart failure, liver cirrhosis, SIADH and nephrotic syndrome. A series of orally active nonpeptide antagonists against the vasopressin receptor subtypes has recently been synthesized and is now under intensive examination. Nonpeptide V1a-receptor specific antagonists, OPC 21268 and SR 49059, nonpeptide V2-receptor specific antagonists, SR 121463 A and VPA 985, and combined V1a-/V2-receptor antagonists, OPC 31260 and YM 087, have become available for clinical research. AVP-V2-receptor antagonists lead to a dose-dependent diabetes insipidus in animals and man. The term aquaretic drugs (aquaretics) has been coined for these drugs to highlight their different mechanism compared to the saluretic diuretic furosemide. V1a-receptor antagonists might offer new therapeutic advantages in the treatment of vasoconstriction and hypertension. Combined V1a-/V2-receptor antagonists might be beneficial in the treatment of congestive heart failure. Early results are promising and now need to be confirmed in large clinical studies.

[Monosymptomatic hyperthyroidism and TSH-producing adenoma: successful therapy with octreotide]. / Monosymptomatische Hyperthyreose und TSH-produzierendes Adenom: Erfolgreiche Therapie mit Octreotid.

HISTORY AND FINDINGS: Magnetic resonance imaging (MRI) of the central nervous system was performed on a 72-year-old woman who was hyperthyroid without suppression of the thyroid-stimulating hormone (TSH) and had complained of a recent onset of headaches. MRI demonstrated a space-occupying lesion, 1 cm in diameter, in the anterior pituitary. The clinical symptoms were marked by a long-standing monosymptomatic illness of rapidly changing mood swings with depressive and manic phases. INVESTIGATIONS: Endocrinological-biochemical tests showed hyperthyroidism (fT3 10.55 pmol/l and fT4 39 pmol/l) but no TSH suppression (TSH: 2.9 microU/ml). Octreotide scintigraphy documented an activity-rich area in the anterior pituitary and the upper anterior mediastinum. Mediastinal MRI revealed a 5 cm space-occupying mass lying on the right atrium. 131I scintigraphy identified the mass as a retrosternal goitre. TREATMENT AND COURSE: As an operation on the anterior pituitary would have carried a high risk for the patient who was in a poor general condition and she had refused to be operated, treatment with octreotide, a long-acting somatostatin analogue, was initiated. This achieved a euthyroid state with partly suppressed TSH, and the patient's emotional swings ceased. CONCLUSION: If hyperthyroidism coexists with non-suppressed TSH levels, a TSH-producing hypophyseal adenoma should be considered in the differential diagnosis despite its rarity. Octreotide administration is an effective and safe treatment and is the method of choice, especially when there are contraindications to surgical resection of the anterior pituitary.

[Disposable protection for flexible gastroenterologic endoscopy: prospective comparative evaluation of a new gastroscopy system (Endosheath) compared to the standard fiberglass gastroscope]. / Einmalschutzhülle für die flexible gastroenterologische Endoskopie: prospektiv vergleichende Evaluation eines neuen Gastroskopsystems (= Endosheath) im Vergleich zum Standard-Glasfasergastroskop.

The reprocessing of flexible gastrointestinal endoscopes is time-consuming and expensive. Endoscopically transmitted infections due to insufficient disinfection are already of clinical importance. A new developed prototype of a flexible, fiberoptic gastroscope was tested in a prospective open randomized trial to evaluate the function. reprocessing and hygienical safety of this disposable, sheathed endoscopic system and was compared with a standard gastroscope. This new endoscopical system utilizes a disposable sheath to cover and protect all working surfaces of the endoscope from contamination. A prospective, randomized trial was performed in our unit to compare the disposable gastroscope (G-F100) with a standard-gastroscope of the newest Generation (GIF-Q 30). Visual analog rating scales were used to record evaluations of endoscope performance and reprocessing by endoscopists and reprocessing personnel. We recorded the time of reprocessing, the time to perform the procedures, depth of insertion, total instrument downtime and any problems which occurred during the procedure. Microbiological swabs were taken from each endoscope. 40 procedures (20 standard, 20 sheathed) were performed. The sheathed gastroscope 8.9 min versus 7.1 min. The overall instrument downtime was significantly shortened by the endosheath (9.8 min versus 47.5 min with the standard gastroscope). The disposable gastroscope-system permits an increase of procedure-frequency up to a factor of 2.9. The standard gastroscope was preferred by the endoscopists and the reprocessing personnel. No microbiological contaminations of the sheathed or the standard gastroscopes could be demonstrated, and no leak of the sheaths was recorded after gastroscopy. The disposable gastroscope has important advantages of decreased instrument turn-around time and potentially increased staff and patient safety.