Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice.

Stress exposure during the sensitive period of early development has been shown to program the brain and increases the risk to develop cognitive deficits later in life. We have shown earlier that early-life stress (ES) leads to cognitive decline at an adult age, associated with changes in adult hippocampal neurogenesis and neuroinflammation. In particular, ES has been shown to affect neurogenesis rate and the survival of newborn cells later in life as well as microglia, modulating their response to immune or metabolic challenges later in life. Both of these processes possibly contribute to the ES-induced cognitive deficits. Emerging evidence by us and others indicates that early nutritional interventions can protect against these ES-induced effects through nutritional programming. Based on human metabolomics studies, we identified various coffee-related metabolites to be part of a protective molecular signature against cognitive decline in humans. Caffeic and chlorogenic acids are coffee-polyphenols and have been described to have potent anti-oxidant and anti-inflammatory actions. Therefore, we here aimed to test whether supplementing caffeic and chlorogenic acids to the early diet could also protect against ES-induced cognitive deficits. We induced ES via the limited nesting and bedding paradigm in mice from postnatal(P) day 2-9. On P2, mice received a diet to which 0.02% chlorogenic acid (5-O-caffeoylquinic acid) + 0.02% caffeic acid (3',4'-dihydroxycinnamic acid) were added, or a control diet up until P42. At 4 months of age, all mice were subjected to a behavioral test battery and their brains were stained for markers for microglia and neurogenesis. We found that coffee polyphenols supplemented early in life protected against ES-induced cognitive deficits, potentially this is mediated by the survival of neurons or microglia, but possibly other mechanisms not studied here are mediating the effects. This study provides additional support for the potential of early nutritional interventions and highlights polyphenols as nutrients that can protect against cognitive decline, in particular for vulnerable populations exposed to ES.

Assessing the contribution of the chemical exposome to neurodegenerative disease.

Over the past few decades, numerous environmental chemicals from solvents to pesticides have been suggested to be involved in the development and progression of neurodegenerative diseases. Most of the evidence has accumulated from occupational or cohort studies in humans or laboratory research in animal models, with a range of chemicals being implicated. What has been missing is a systematic approach analogous to genome-wide association studies, which have identified dozens of genes involved in Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. Fortunately, it is now possible to study hundreds to thousands of chemical features under the exposome framework. This Perspective explores how advances in mass spectrometry make it possible to generate exposomic data to complement genomic data and thereby better understand neurodegenerative diseases.

Association of a MIND Diet with Brain Structure and Dementia in a French Population.

BACKGROUND: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines higher consumption of vegetables, berries, nuts, whole grains, olive oil, fish, beans and poultry, with lower consumption of meat, sugars and saturated fats, is a promising strategy to prevent dementia. However, evidence in populations with non-US food culture, especially from Europe, is limited. OBJECTIVES: To evaluate the association of a French-adapted MIND diet score with gray matter volumes, white matter microstructure and incident dementia. DESIGN AND SETTING: This longitudinal study included participants from the population-based Three-City Bordeaux cohort (≥65 years), with a follow-up from June 2001 to February 2018. PARTICIPANTS: Dementia-free participants at dietary assessment, in 2001-2002, who underwent systematic detection of incident dementia (over up to 7 visits). A subset of the cohort was included in an ancillary MRI study in 2010-2011. MEASUREMENTS: A French-adapted MIND diet score (range, 0-15) was computed from a 148-item Food Frequency Questionnaire and a 24-hour recall administered at home. Incident dementia and its subtypes were adjudicated by an expert committee; and gray matter volumes and white matter microstructure were assessed by 3D-T1 MRI and diffusion-MRI. RESULTS: Among 1,412 participants (mean age, 75.8 [SD, 4.8]; 63% women), followed for a median of 9.7 years (maximum 16.3 years), 356 (25.2%) developed incident dementia. In multivariable-adjusted Cox model, a higher French MIND diet score was associated with lower risks of dementia and AD (hazard ratios for 1-point of score = 0.89 [95% confidence interval, 0.83-0.95] and 0.88 [0.81-0.96], respectively). In Tract-Based Spatial Statistics analysis of 175 participants included in the MRI sub-study, a higher MIND diet score was associated with lower diffusivity values in the splenium of the corpus callosum (P < .05 after Family-Wise Error-correction). In contrast, there was no significant association of the adapted MIND diet score with gray matter volumes in Voxel-Based Morphometry analysis. CONCLUSION: In this cohort of French older adults, higher adherence to the French MIND diet was associated with a lower dementia risk and with preserved white matter microstructure. These results provide further evidence for a role of the MIND diet in the prevention of dementia.

Changes in breast cancer biomarkers in the IGF1R/PI3K pathway in recurrent breast cancer after tamoxifen treatment.

Development of resistance to the antioestrogen tamoxifen occurs in a large proportion of patients with oestrogen receptor-positive (ER+) breast cancer and is an important clinical challenge. While loss of ER occurs in c.20% of tamoxifen-resistant tumours, this cannot be the sole explanation for tamoxifen treatment failure. PI3K pathway activation, including by insulin-like growth factor receptor 1 (IGF1R), has been implicated in some resistance models. The primary aim was to determine whether evidence exists in clinical breast cancer for a role of IGF1R and/or the PI3K pathway, in acquisition of resistance to tamoxifen. Invasive primary and recurrent tamoxifen-resistant tumours from the same patient (n=77) were assessed for changes in ER, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), IGF1R, stathmin, PTEN expression and PIK3CA mutations where possible. ER and PgR levels were significantly reduced at recurrence with 22 and 45%, respectively, showing negative status at this time. Acquisition of HER2 overexpression occurred in 6% of cases. IGF1R expression was significantly reduced in both ER+ and ER- recurrences and stathmin levels increased. A positive association between stathmin and IGF1R emerged in recurrent samples, despite their opposing relationships with ER, suggesting some coalescence of their activities may be acquired. The data confirm loss of ER and PgR and gain of HER2 in some tamoxifen-resistant tumours. There is no evidence for IGF1R gain in tamoxifen resistance; increases in stathmin levels suggest that activation of the PI3K pathway may have contributed, but PTEN loss and PIK3CA hotspot mutations were relatively rare.

EGFR fluorescence in situ hybridisation assay: guidelines for application to non-small-cell lung cancer.

There is a need for predictive biomarkers that identify non-small-cell lung cancer (NSCLC) patients most likely to respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There are numerous potential candidates, although none has been proven in prospective clinical trials. The EGFR gene copy number evaluated by fluorescence in situ hybridisation (FISH) has been highlighted as one of the most effective markers for sensitivity to EGFR TKIs in large phase III, randomised placebo-controlled trials and has been used in clinical settings to assist physicians in defining the therapeutic regimen. The EGFR FISH assay has technical challenges and it is critical that detailed guidelines are provided to help clinical laboratories in performing and interpreting the test. Excellent assay reproducibility and portability rates among laboratories are crucial to guarantee that accurate clinical decisions can be made for patients with NSCLC. This article discusses the consensus outcomes of a global workshop convened to discuss key technical issues and standardise reading strategies for the EGFR FISH assay of NSCLC tumour tissue.

[Schwannoma of the nasal cavity: a case report]. / Schwannom der Nasenhaupthöhle: Eine Falldarstellung.

Schwannomas of the nasal cavity and paranasal sinuses are quite rare, with 4% occurring in this location. Most of them are benign and do not recur when totally removed by surgery. It is very important to distinguish between schwannoma and primary benign neurofibroma. Neurofibromas are lesions having the possibility for malignant transformation and recurrence. A case of schwannoma in the nasal cavity is reported, and the diagnostic and therapeutic procedures, as well as recommendations from the literature, are described. The histological and immunohistochemical features are discussed in detail to draw a distinction between schwannoma and neurofibroma. In cases of intranasal and paranasal lesions, the existence of a schwannoma must be considered. Differentiating between schwannoma and neurofibroma is important for estimating the risk of malignant transformation and recurrence.

Chronic ataxic neuropathy mimicking dorsal midbrain syndrome.

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies.

[Myxoma and myxoid chondrosarcoma of the nasal septum: two case reports]. / Myxomatöse Neoplasien des Nasenseptums: 2 Fallberichte.

Myxoid neoplasms are histopathologically divided into true myxomas and other tumors of myxomatous character. In the region of the nasal septum, this tumor entity is extremely rare. In the following two case reports, the unusual findings of a myxoma and a myxoid chondrosarcoma of the nasal septum are presented and discussed. At first visit, both patients reported a slowly progressing, bilateral nasal obstruction. In nasal endoscopy, both showed a smoothly surfaced, spheroid, soft tissue mass in the dorsal nasal septum. On CT-scans, a displacing growth was described for the first patient; in the second patient, a bony arrosion of the floor of the sphenoid sinus was suspected. Both lesions were surgically completely removed. The histopathological diagnosis was myxoma in the first and myxoid chondrosarcoma in the second patient. An early, locally recurrent tumor in the second patient could also be surgically removed. Both patients have been in full remission for more than a year. In spite of the similar symptoms and clinical findings, histopathologically different myxoid neoplasms of the nasal septum show marked variations in growth and recurrence.

MR-imaging changes of musculoskeletal soft-tissue sarcomas associated with neoadjuvant chemotherapy and hyperthermia.

PURPOSE: To evaluate early changes in musculoskeletal soft-tissue sarcomas under neoadjuvant chemotherapy combined with regional hyperthermia (RHT). PATIENTS AND METHODS: Nineteen consecutive patients with high-grade soft-tissue sarcomas of the musculoskeletal system were treated with neoadjuvant chemotherapy combined with RHT. Patients were imaged, using a high field MR-scanner, before onset of therapy, immediately after one and after four cycles of therapy. The images were evaluated for volume reduction and development of tumour necrosis. In addition, side effects such as surrounding soft-tissue oedema, bleeding and muscle or bone marrow necrosis were analysed. RESULTS: Tumour volume reduction was significant after the completion of neoadjuvant therapy (mean 49%, range 5-91%; (p < 0.001). Extent of tumour necrosis was also significantly different before (mean 22%) and after therapy (mean 58%, p < 0.001). Three patients showed strong tumour necrosis already after one cycle of treatment. Tumour volume reduction was not associated with the extent of pre-existing necrosis or necrosis development. The extent of tumour volume before start of therapy did not affect volume reduction or necrosis induction after therapy. Reduction of tumour oedema was significant after therapy (p < 0.001). No side effects were observed during thermochemotherapy. CONCLUSION: Neoadjuvant chemotherapy combined with RHT resulted in significant tumour volume reduction and induction of tumour necrosis, which can be detected early and monitored closely with MRI.

Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors.

The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are only partially known. Up to now, mainly numerical chromosomal aberrations have been described. Therefore we performed a comprehensive study on paraffin-embedded material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y) combining comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X; DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67). By DNA cytometry, 16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in 5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%). The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6 cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%), mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from 0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic analysis, provided statistically significant prognostic information. In summary, our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our observations confirm earlier reports that trisomy 12 and 14 are frequent aberrations; however, monosomy 22 seemingly is even more prevalent.

Interindividual variability of surface EMG changes during cycling exercise in healthy humans.

We studied surface electromyogram (SEMG) changes during 1-h endurance cycling in 12 healthy subjects of whom five were involved in mountain bike training programme. The work load was set at 50% of the predicted maximal heart rate. The surface EMG and the compound evoked muscle action potential (M-wave) from the vastus lateralis muscle were recorded at rest, during the 1-h cycling period, and the 20-min recovery period. The root mean square (RMS) and the median frequency (MF) of SEMG power spectrum were computed. In all subjects, there was no shift in the median frequency throughout the cycling period and the increase in RMS remained stable. In subjects untrained to endurance cyclism, the M-wave duration increased at the end of the cycling period and these changes persisted for a consecutive 15-min period during recovery of exercise. By contrast, in trained mountain bikers the M-wave duration decreased after 2 min of exercise--the effect persisting for 2 min during recovery. These data suggest that the interpretation of M-wave changes during cycling must take into consideration the sport practices of the subjects and also that SEMG power spectrum and M-wave explore different electrophysiological events.

Fluorescence staining of oral cancer using a topical application of 5-aminolevulinic acid: fluorescence microscopic studies.

INTRODUCTION: Topical application of 5-aminolevulinic acid (5-ALA) by means of a rinsing solution has been shown to be a promising new procedure in the diagnosis of oral malignancies. However, for assessing the reliability of this method regarding fluorescence-guided tumor resections and photodynamic therapy, further information on the distribution and penetration depth of 5-ALA-induced protoporphyrin IX (PPIX) in the tissue is needed. METHODS: 24 patients suffering from oral cancer were included in this investigation. Biopsies were taken immediately after fluorescence examination and either used as native sections for immediate fluorescence microscopic examination (n = 3) or shock frozen in liquid nitrogen and prepared as frozen sections (n = 46). Fluorescence imaging and digital image processing were utilized in order to determine the presence of PPIX in regions of various histologies as well as the penetration depth of PPIX into solid tumor. RESULTS: PPIX fluorescence in the tissue was limited to the epithelium. Both normal and dysplastic epithelium showed PPIX fluorescence. In the stroma, no PPIX fluorescence was found. In some cases (n = 3/4) invasive carcinomas did not show PPIX fluorescence, while the adjacent or overlying normal epithelium was strongly fluorescent. The penetration depth of PPIX after topical application of 5-ALA was found to be limited to less than 1 mm. CONCLUSION: PPIX fluorescence induced by topical application of 5-ALA can be very useful in the determination of superficial tumor margins. However, due to the limited penetration depth there is a risk of not accurately recognizing the infiltration depth of solid tumors. The aim of further investigations will be to assess the tissue distribution and depth of penetration of PPIX following systemic application of 5-ALA.

Diffusion-weighted imaging of tumor recurrencies and posttherapeutical soft-tissue changes in humans.

The aim of this study was to examine soft tissue tumor recurrences and posttherapeutic soft tissue changes in humans with a diffusion-weighted steady-state free precession (SSFP) sequence. Twenty-four patients with 29 pathologies of the pelvis or the extremities were examined. The lesions were classified as follows: group 1, recurrent viable tumors (n = 10); group 2, postoperative hygromas (n = 7); and group 3, posttherapeutic reactive inflammatory muscle changes (n = 12). The sequence protocol in these patients consisted of short tau inversion recovery images, T2-weighted spin-echo (SE), pre- and postcontrast T1-weighted SE images and the diffusion-weighted SSFP sequence. The signal loss on diffusion-weighting was evaluated visually on a four-grade scale and quantitatively. The signal intensities were measured in regions of interest and a regression analysis was performed. Statistical analyses was performed utilizing the Student's t-test. The signal loss was significantly higher for hygromas and edematous muscle changes than for recurrent tumors (p < 0.001) indicating higher diffusion of water protons. The regression coefficient was -0.11 (mean) for tumors. Hygromas had a significantly higher signal loss than inflammatory edematous muscle changes (p < 0.01). The regression coefficients were -0.29 (mean) for hygromas and -0.22 (mean) for edematous muscle changes. The SSFP sequence seems to be a suitable method for diffusion-weighted imaging of the musculoskeletal system in humans. These preliminary results suggest that the signal loss and the regression coefficients can be used to characterize different types of tissue.

Effects of endogenous nitric oxide in activation of group IV muscle afferents.

Based on previous observations that acute hypoxemia, which enhances nitric oxide (NO) production, depresses the activation of group IV afferents after repetitive low-frequency muscle stimulation (MS), we hypothesized that endogenous NO modulates the response of these nerve endings to their specific stimuli. The present study in rabbits examined the effects of a blocker of NO synthase (NG-nitro-L-arginine methyl ester L, L-NAME) and an exogenous NO donor (3-morpholinosydnonimine, SIN-1) on the group IV afferents of tibialis anterior. The efficacy of the two test agents was judged by their effects on systemic blood pressure. L-NAME markedly elevated (+46%) the resting discharge rate of group IV afferents but abolished their activation after repetitive MS. After SIN-1 injection, there was a transient decrease in blood pressure, which correlated well with a lowered resting discharge rate of group IV afferents. SIN-1 infusion caused a stable reduction of blood pressure; the resting afferent nerve discharge rate began first to decrease but then recovered control mean values. SIN-1 infusion abolished the activation of group IV afferents after MS. This study indicates that endogenous NO production in a resting or contracting muscle attenuates the baseline activity of group IV muscle afferents and their activation after repetitive muscle contractions.

Diagnostic value of increased diffusion weighting of a steady-state free precession sequence for differentiating acute benign osteoporotic fractures from pathologic vertebral compression fractures.

BACKGROUND AND PURPOSE: Differentiating acute benign from neoplastic vertebral compression fractures can pose a problem in differential diagnosis on routine MR sequences, as signal changes can be quite similar. Our purpose was to assess the value of increasing the diffusion weighting of a diffusion-weighted steady-state free precession (SSFP) sequence for differentiating these two types of vertebral compression fractures. METHODS: Twenty-nine patients with 32 acute vertebral compression fractures caused by osteoporosis (n = 15) or malignancy (n = 17) were examined with a diffusion-weighted SSFP sequence, a T1-weighted spin-echo sequence, and a short-inversion-time inversion recovery sequence. The SSFP sequence was performed with increased diffusion weighting (delta = 0.6, 3.0, 6.0, and 9.0 ms). The signal intensities of the fractured vertebral bodies were rated on a five-point scale from markedly hypointense to markedly hyperintense relative to normal adjacent vertebral bodies. Quantitative analysis was performed by region-of-interest measurements and by calculating the bone marrow contrast ratio. Statistical analysis was performed with the Mann Whitney U test and Student's t test. RESULTS: At delta = 3 ms, the osteoporotic fractures yielded hypointense signal in seven cases, isointense signal in six, and hyperintense signal in two. The fractures showed a progressive signal loss with increased diffusion weighting, so that hypointensity was reached in all but one case. All metastatic fractures had hyperintense signal with delta = 3 and 6.0 ms. With delta = 9.0 ms, four fractures became isointense. CONCLUSION: Increasing diffusion weighting can reduce false-positive hyperintense osteoporotic fractures or make hypointensity more obvious in cases of osteoporotic fractures.

Influence of oxygen supply on activation of group IV muscle afferents after low-frequency muscle stimulation.

Anaerobic muscle metabolism and local release of inflammatory mediators play key roles in the mechanism of postfatigue-induced activation of group IV muscle afferents. The present study focused on activation of these muscle afferents after a 3-min period of low-frequency muscle stimulation (LFMS) in different conditions of muscle oxygenation, such as occur in patients with respiratory insufficiency and subjects living at high altitude. In anesthetized rabbits, spontaneous activity of group IV afferents (conduction velocity = 1.52 +/- 0.13 m.s(-1)) from the tibialis anterior muscle was recorded at rest (baseline) and then after LFMS under normoxic (PaO(2) = 113 mmHg), hyperoxic (PaO(2) = 186 mmHg), or hypoxic (PaO(2) = 35 mmHg) conditions. The maximal force decay at the end of LFMS did not differ significantly with respect to conditions of muscle oxygenation. Compared with normoxia, hypoxia significantly increased the baseline activity of group IV muscle afferents, whereas no effect was noted when hypoxia followed a period of hyperoxia. LFMS-induced activation of group IV afferents occurred in all circumstances, except when hypoxia was first tested. The activation of group IV muscle afferents after LFMS was markedly reduced when hypoxia followed normoxia (+14% versus +27%) or hyperoxia (+55% versus +144%), whereas it was accentuated when hyperoxia followed hypoxia (+25% versus +8%). We concluded that the sensorimotor control of skeletal muscles may be altered during acute hypoxia but facilitated after reoxygenation.

Response of the rabbit diaphragm to tendon vibration.

To evaluate the potential role of diaphragmatic muscle spindles in the act of breathing, we have recorded the electromyograms of the diaphragm and the external intercostal muscle in the third interspace during high-frequency mechanical vibration (50 Hz) of the central tendon in eight anesthetized, spontaneously breathing rabbits. Vibration induced a consistent, clear-cut increase in the inspiratory activity recorded from the external intercostal, thus indicating that the mechanical stimulus applied to the diaphragm was strong enough to trigger muscle spindles at distant sites. However, vibration did not elicit any alteration in costal or crural diaphragmatic activity in any animal. Similarly, when vibration was applied during hyperventilation-induced apnea, activity was recorded in the external intercostal but not in the diaphragm. These observations support the traditional view that the diaphragm is poorly endowed with muscle spindles and that these play little or no significant role in the act of breathing.

Detection of squamous cell carcinoma of the oral cavity by imaging 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.

OBJECTIVES: Early cancer detection is the best way to improve the prognosis of patients with oral cancer. Therefore this study presents quantitative fluorescence measurements and results in the visualization of cancerous oral mucosa with 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX). METHODS: Time progression and type of porphyrin accumulation were analyzed in neoplastic and surrounding healthy tissue of 58 patients with a suspected cancer of the oral cavity by measuring emission spectra of 5-ALA-induced PPIX fluorescence. Fluorescence images in the red and green spectral range from the tumor tissue were recorded with a charge-coupled device camera. RESULTS: After topical application of 0.4% 5-ALA and incubation for 1 to 2.5 hours, all patients revealed higher intensities of red fluorescence in neoplastic tissue compared with the surrounding normal tissue. Maximum contrast was reached after 1.5 hours of incubation. In 13.8% (n = 8) of the patients, additional findings like dysplasia, carcinoma in situ, primary tumor, secondary carcinomas, and tumor branches were found by means of fluorescence marking in contrast to white light examination. An evaluation of the biopsy specimens resulted in a specificity of 60% and a sensitivity of 99%. CONCLUSIONS: As a fluorescent marker, PPIX could represent a possible new diagnostic tool to detect early malignant and secondary lesions in the oral cavity. In addition, 5-ALA-induced PPIX fluorescence is promising as a useful intraoperative tool for determining adequate surgical margins of resection. Further investigations aim to assess this diagnostic procedure as a sensitive and clinically reliable method for patients with oral cancer.

Fluorescence staining of laryngeal neoplasms after topical application of 5-aminolevulinic acid: preliminary results.

BACKGROUND AND OBJECTIVE: The prognosis of patients suffering from laryngeal carcinomas can be improved by early diagnosis. Exact demarcation of tumor margins could contribute to an optimum preservation of the larynx. Therefore, the aim of the present study was the evaluation of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence as a new diagnostic procedure for the detection of laryngeal cancer. STUDY DESIGN/MATERIALS AND METHODS: Sixteen patients with suspected malignancies of the larynx received 0.6 wt% 5-ALA-NaCl solution by means of a medical nebulizer. After a period of 1-2 hours, the patients underwent microlaryngoscopy under white light and fluorescence illumination (lambda(ex) = 375-440 nm). A quantitative analysis of the fluorescence contrast between neoplastic and surrounding tissue was performed using an optical multichannel analyzer. RESULTS: Carcinoma, carcinoma in situ, and dysplasia showed red fluorescence that could be attributed to the 5-ALA-induced formation of PPIX. The surrounding normal tissue exhibited autofluorescence in the green spectral range, which was greatly reduced within the tumor. The results of macroscopic red fluorescence staining were correlated with the histologic diagnosis. CONCLUSION: According to these preliminary results, the presented method seems to be a promising adjunct diagnostic procedure for the early identification of malignant neoplasms in the larynx. The aim of further investigations is the assessment of sensitivity and specificity and an evaluation of fluorescence-guided laser resections of laryngeal cancer. Lasers Med. Surg. 25:414-420, 1999.