Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures.

Boron neutron capture therapy (BNCT) is a binary cancer treatment modality where two different agents (10B and thermal neutrons) have to be present to produce an effect. A dedicated trial design is necessary for early clinical trials. The concentration of 10B in tissues is an accepted surrogate to predict BNCT effects on tissues. Tissue, blood, and urines were sampled after infusion of two different boron carriers, namely BSH and BPA in the frame of the European Organisation for Research and Treatment of Cancer (EORTC) trial 11001. In this study, urine samples were used to identify protein profiles prior and after drug infusion during surgery. Here, an approach that is based on the mass spectrometry (MS)-based proteomic analysis of urine samples from head and neck squamous cell carcinoma (HNSCC) and thyroid cancer patients is presented. This method allowed the identification of several inflammation- and cancer-related proteins, which could serve as tumor biomarkers. In addition, changes in the urinary proteome during and after therapeutic interventions were detected. In particular, a reduction of three proteins that were involved in inflammation has been observed: Galectin-3 Binding Protein, CD44, and osteopontin. The present work represents a proof of principle to follow proteasome changes during complex treatments based on urine samples.

Modified Nucleosides - Molecular Markers Suitable for Small-volume Cancer?

BACKGROUND: Modified nucleosides (mNS) in urine are shown to be encouraging markers in cancer, mostly in patients presenting with high tumor mass such is breast and lung cancer. To our knowledge, mNS have not been investigated in head and neck squamous cell carcinoma (HNSCC). HNSCC is characterized by early metastasis into locoregional lymph nodes and slow infiltrating growth, but even in the advanced stage exhibits only a relatively low cancer volume. Therefore, reliable distinction between HNSCC and healthy controls by urinary mNS might pose substantial analytical problems and even more as patients with HNSCC mostly have an increased exposure to tobacco smoke and excessive alcohol consumption which affect the renal mNS pattern. MATERIALS AND METHODS: Urinary mNS in samples of 93 therapy-naive patients with HNSCC and 242 healthy controls were quantified by reversed-phase high-performance liquid chromatography. Considering that the circadian rhythm causes diuresis-induced variations in concentration, the mNS-to-creatinine ratio was chosen to compare patients and controls. For sensitivity and specificity in discriminating between patients and controls, the corresponding curve was plotted. Additionally, logistic regression was carried out and a multilayer perceptron neuronal network (NN) was created. RESULTS: Fifteen mNS were detectable in cases and controls; concentrations of 11 were found to be significantly different. The sensitivity and specificity depend on the total volume of the lesion; HNSCC with volume <20 ml was reliably detected, but those with a volume of 20 ml or greater produced amounts of mNS which led to the most accurate detection of HNSCC based on HNSCC-specific mNS patterns. CONCLUSION: Analysis of urinary mNS allows for detection of small-volume HNSCC, with acceptable specificity and sensitivity if the tumor volume exceeds 20 ml.

The volatilome - investigation of volatile organic metabolites (VOM) as potential tumor markers in patients with head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: Different organisms such as bacteria, molds and humans produce and release a relative unknown class of metabolites which are responsible for the individual olfactory pattern. These volatile organic metabolites (VOM) represent a kind of biosignature that reflects the sum of all multifactorial influences, including genetics, environmental factors, nutritional and disease status. As a result of pathological processes the individual body odor can be influenced by newly produced or altered compositions of the VOM. Until now, human VOM have been detected in various body media, such as on the skin, in the exhaled air as well as in body fluids such as saliva, mother's milk, sweat, blood and urine. METHODS: In this retrospective case-control study urinary VOM of 53 therapy-naive patients with head and neck squamous cell carcinoma (HNSCC) and 82 healthy controls were semi-quantified by headspace solid-phase micro extraction (SPME) gas chromatography (GC) mass spectrometry (MS). At first, the procedure was optimized in respect to the extraction parameters. By using Student's t-test significant differences in the VOM pattern with the corresponding p-values were obtained. For multivariate metabolite pattern recognition the hierarchical cluster analysis by Ward was applied, followed by the supervised partial least squares-discriminant analysis (PLS-DA). RESULTS: In total 81 VOMs could identified in the urine samples of all study participants, of which 25 were significantly increased and of which were 10 significantly reduced in HNSCC-patients compared to the controls. In addition, the multivariate statistics confirmed that on the basis of the renal excreted pattern of the volatile metabolites a high discrimination can be carried out between patients with a tumor in the head and neck region and controls. The substance group of the saturated, unbranched aldehydes makes a substantial contribution in this context. CONCLUSIONS: The systematic pattern analysis of urinary VOMs appears to have potential clinical application as a diagnostic tool for cancer, especially HNSCC.

High Level of Tobacco Carcinogen-Derived DNA Damage in Oral Cells Is an Independent Predictor of Oral/Head and Neck Cancer Risk in Smokers.

Exposure to tobacco-specific nitrosamines (TSNA) and polycyclic aromatic hydrocarbons (PAH) is recognized to play an important role in the development of oral/head and neck squamous cell cancer (HNSCC). We recently reported higher levels of TSNA-associated DNA adducts in the oral cells of smokers with HNSCC as compared with cancer-free smokers. In this study, we further investigated the tobacco constituent exposures in the same smokers to better understand the potential causes for the elevated oral DNA damage in smokers with HNSCC. Subjects included cigarette smokers with HNSCC (cases, n = 30) and cancer-free smokers (controls, n = 35). At recruitment, tobacco/alcohol use questionnaires were completed, and urine and oral cell samples were obtained. Analysis of urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and N'-Nitrosonornicotine (NNN; TSNA biomarkers), 1-hydroxypyrene (1-HOP, a PAH), cotinine, 3'-hydroxycotinine, and the nicotine metabolite ratio (NMR) were performed. Cases and controls differed in mean age, male preponderance, and frequency of alcohol consumption (but not total alcoholic drinks). Univariate analysis revealed similar levels of NNN, 1-HOP, and cotinine between groups but, as reported previously, significantly higher DNA adduct formation in the cases. Multiple regression adjusting for potential confounders showed persistent significant difference in DNA adduct levels between cases and controls [ratio of geometric means, 20.0; 95% CI, 2.7-148.6). Our cohort of smokers with HNSCC demonstrates higher levels of TSNA-derived oral DNA damage in the setting of similar exposure to nicotine and tobacco carcinogens. Among smokers, DNA adduct formation may act as a predictor of eventual development of HNSCC that is independent of carcinogen exposure indicators. Cancer Prev Res; 10(9); 507-13. ©2017 AACRSee related editorial by Johnson and Bauman, p. 489.

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients.

Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) plays a role in the development and progression of epithelial malignancies. Measurements of urinary PGE-M, a stable metabolite of PGE2, reflect systemic PGE2 levels. Here, we investigated whether urinary PGE-M levels were elevated in healthy tobacco users and in patients with oral squamous cell carcinoma (OSCC). Median urinary PGE-M levels were increased in healthy tobacco quid chewers [21.3 ng/mg creatinine (Cr); n = 33; P = 0.03] and smokers (32.1 ng/mg Cr; n = 31; P < 0.001) compared with never tobacco quid chewers-never smokers (18.8 ng/mg Cr; n = 30). Urinary PGE-M levels were also compared in OSCC patients versus healthy tobacco users. An approximately 1-fold increase in median urinary PGE-M level was found in OSCC patients (48.7 ng/mg Cr, n = 78) versus healthy controls (24.5 ng/mg Cr, n = 64; P < 0.001). We further determined whether baseline urinary PGE-M levels were prognostic in OSCC patients who underwent treatment with curative intent. A nearly 1-fold increase in baseline urinary PGE-M levels (64.7 vs. 33.8 ng/mg Cr, P < 0.001) was found in the group of OSCC patients who progressed (n = 37) compared with the group that remained progression free (n = 41). Patients with high baseline levels of urinary PGE-M had both worse disease-specific survival [HR, 1.01 per unit increase; 95% confidence interval (CI), 1.01-1.02; P < 0.001] and overall survival (HR, 1.01 per unit increase; 95% CI, 1.00-1.02; P = 0.03). Taken together, our findings raise the possibility that NSAIDs, prototypic inhibitors of PGE2 synthesis, may be beneficial for reducing the risk of tobacco-related aerodigestive malignancies or treating OSCC patients with high urinary PGE-M levels. Cancer Prev Res; 9(6); 428-36. ©2016 AACR.

Tobacco use and surgical outcomes in patients with head and neck cancer.

BACKGROUND: Tobacco use is a risk factor for head and neck cancer, but effects on postoperative outcomes are unclear. METHODS: Patients with head and neck cancer (n = 89) were recruited before surgery. We assessed self-reported tobacco use status (never, former, or current) at study entry and recent tobacco exposure via urinary cotinine on surgery day. Outcomes included hospital length of stay (LOS) and complications. RESULTS: Most participants reported current (32.6%) or former (52.8%) tobacco use; 43.2% were cotinine-positive on surgery day. Complications occurred in 41.6% and mean LOS was 4.0 and 8.8 days in patients who received low and high acuity procedures, respectively. Current and former smokers were over 6 times more likely to have complications than never smokers (p = .03). For high acuity procedures, LOS was increased in current (by 4.4 days) and former smokers (by 2.3 days; p = .02). CONCLUSION: Tobacco use status is associated with postoperative complications and may distinguish at-risk patients.

Catecholamine-Synthesizing Enzymes Are Expressed in Parasympathetic Head and Neck Paraganglioma Tissue.

BACKGROUND/AIM: Increased dopamine production may be a feature of head and neck paraganglioma (HNPGL). 18F-fluorodihydroxyphenylalanine positron emission tomography scintigraphy has a high sensitivity for detecting HNPGLs. These observations strongly suggest that HNPGLs have the capacity for L-3,4-dihydroxyphenylalanine uptake and conversion towards dopamine. Therefore, our aim was to demonstrate the presence of catecholamine-synthesizing enzymes, i.e. tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC) and dopamine ß-hydroxylase (DBH) in HNPGL tissue. METHODS: A single-center study was performed among patients who underwent surgery for HNPGL at a single university referral center between 1994 and 2012. HNPGL tissue was immunohistochemically stained for TH, AADC and DBH. Data on paraganglioma-associated germline mutations, preoperative biochemical phenotype and imaging studies were retrieved. Catecholamine excess was defined as preoperative plasma and/or urinary levels of metanephrine, normetanephrine or 3-methoxytyramine above the upper reference limit. RESULTS: Nineteen HNPGLs from 18 patients were evaluated. All tumor tissues (100%) stained positive for AADC, 6 (32%) for TH and 2 (11%) for DBH. Of 3 HNPGLs staining positive for DBH, 2 were also positive for AADC and TH. Catecholamine excess was only present in 1 patient (5%). The HNPGLs of this single patient only showed positive staining for AADC. CONCLUSIONS: Catecholamine-synthesizing enzymes, in particular AADC, are expressed in the majority of HNPGL tissues.

Evaluation of the cisplatin nephrotoxicity using the urinary neutrophil gelatinase-associated lipocalin (NGAL) in patients with head and neck cancer.

INTRODUCTION: Acute kidney injury (AKI) in patients receiving cisplatin is common, therefore the evaluation of renal function in patients on use of nephrotoxic drugs is fundamental. OBJECTIVE: To evaluate the incidence of AKI and the role of lipocalin associated to neutrophil gelatinase (NGAL) in the monitoring of renal function in patients with head and neck cancer (HNC) who received cisplatin. METHODS: We prospectively studied 50 patients with HNC treated with three sessions of cisplatin. Blood and urine were collected 24 hours before cisplatin, 24 hours after infusion, 48 hours after each application and 35 days after the end of treatment (urine NGAL, C-reactive protein, creatinine, glomerular filtration rate, plasma lactate dehydrogenase and magnesium). RESULTS: AKI was observed in 78% of patients. There was increase in creatinine, and decrease in GFR after each cycle of cisplatin, and increased urine NGAL. Positive association was observed between the levels of NGAL, creatinine and C-reactive protein. It was observed an increase in creatinine, NGAL, C-reactive protein and decreased GFR in AKI patients compared to patients without AKI. CONCLUSION: AKI was noted in 78% of patients with HNC treated with cisplatin and showed the correlation of NGAL with creatinine and GFR in demonstrating renal injury. NGAL levels may be elevated compared to baseline levels, even before the use of cisplatin.

Papel da lipocalina associada à gelatinase neutrofílica (NGAL) urinária na nefrotoxicidade da cisplatina em pacientes com câncer de cabeça e pescoço / Evaluation of the cisplatin nephrotoxicity using the urinary neutrophil gelatinase-associated lipocalin (NGAL) in patients with head and neck cancer

Introdução: A injúria renal aguda (IRA) em pacientes que recebem a cisplatina é comum, portanto, a avaliação da função renal em pacientes utilizando drogas nefrotóxicas é fundamental. Objetivo: Avaliar a incidência da IRA e o papel da lipocalina associada à gelatinase neutrofílica (NGAL) na avaliação da função renal em pacientes com câncer de cabeça e pescoço (CCP) que receberam a cisplatina. Métodos: Foram avaliados prospectivamente 50 pacientes com CCP, tratados com três sessões de cisplatina. Foram coletados sangue e urina 24 horas antes da cisplatina, 24 horas após a infusão, 48 horas após cada aplicação e 35 dias após o término do tratamento (NGAL urinária, proteína C reativa, creatinina e taxa de filtração glomerular, desidrogenase lática e magnésio plasmáticos). Resultados: A IRA foi observada em 78% dos pacientes. Houve aumento na creatinina, ureia e queda na TFG após cada ciclo de cisplatina, e aumento da NGAL urinária. Foi observada associação positiva entre os níveis de NGAL e a creatinina e PCR. Evidenciou-se um aumento dos níveis de creatinina, NGAL, PCR e diminuição da TFG nos pacientes com IRA em relação aos pacientes sem IRA. Conclusão: Observamos IRA em 78% dos pacientes avaliados com CCP tratados com a cisplatina e correlação da NGAL com a creatinina e a TFG em demonstrar lesão renal. Os níveis de NGAL podem estar elevados em relação aos níveis basais, mesmo antes da utilização da cisplatina. .

Introduction: Acute kidney injury (AKI) in patients receiving cisplatin is common, therefore the evaluation of renal function in patients on use of nephrotoxic drugs is fundamental. Objective: To evaluate the incidence of AKI and the role of lipocalin associated to neutrophil gelatinase (NGAL) in the monitoring of renal function in patients with head and neck cancer (HNC) who received cisplatin. Methods: We prospectively studied 50 patients with HNC treated with three sessions of cisplatin. Blood and urine were collected 24 hours before cisplatin, 24 hours after infusion, 48 hours after each application and 35 days after the end of treatment (urine NGAL, C-reactive protein, creatinine, glomerular filtration rate, plasma lactate dehydrogenase and magnesium). Results: AKI was observed in 78% of patients. There was increase in creatinine, and decrease in GFR after each cycle of cisplatin, and increased urine NGAL. Positive association was observed between the levels of NGAL, creatinine and C-reactive protein. It was observed an increase in creatinine, NGAL, C-reactive protein and decreased GFR in AKI patients compared to patients without AKI. Conclusion: AKI was noted in 78% of patients with HNC treated with cisplatin and showed the correlation of NGAL with creatinine and GFR in demonstrating renal injury. NGAL levels may be elevated compared to baseline levels, even before the use of cisplatin. .

Urinary neopterin concentration and toxicity of radiotherapy in patients with head and neck carcinoma during external beam radiation.

AIM: Increased serum or urinary concentrations of neopterin are predictive of poor prognosis in patients with tumors across a spectrum of primary locations. Less information is available about the significance of changes of urinary neopterin concentrations during therapy. The aim of the present study was to examine the association between urinary neopterin and toxicity of radiotherapy. PATIENTS AND METHODS: We analyzed changes of urinary neopterin and toxicity of therapy in 12 patients with head and neck carcinoma during external-beam radiation. Urinary neopterin was determined daily by high-performance liquid chromatography. RESULTS: In addition to a trend for increased neopterin concentrations during radiation therapy, a significant association between changes of neopterin and toxicity and vice versa was observed with a rise of neopterin predicting a later manifestation of toxicity as well as manifestion of toxicity predicting a later rise of neopterin. CONCLUSION: Urinary neopterin is predictive of toxicity in patients with head and neck carcinoma. An association between toxicity and subsequent rise of urinary neopterin concentrations was also observed.

Plasma levels of free metanephrines and 3-methoxytyramine indicate a higher number of biochemically active HNPGL than 24-h urinary excretion rates of catecholamines and metabolites.

CONTEXT: A substantial number of patients with head and neck paragangliomas (HNPGLs) have biochemically active tumors, evidenced by increased urinary excretion of catecholamines and metabolites, including 3-methoxytyramine (3MT). It is unclear whether plasma levels of these parameters are more sensitive to detect biochemical activity in HNPGL patients than urinary excretion rates. OBJECTIVE: To compare plasma free levels vs urinary excretion rates of deconjugated 3MT and combined metanephrines (MNs) in patients with HNPGL. PATIENTS AND METHODS: We included 124 consecutive patients with HNPGL for screening of catecholamine excess by measurement of 24-h urinary excretion rates of deconjugated (nor)metanephrine, (nor)epinephrine, dopamine, vanillylmandelic acid, 3MT, and plasma free levels of (nor)metanephrine and 3MT. RESULTS: Plasma free 3MT levels were increased in 35 of the 124 patients (28%), whereas 24-h urinary excretion of deconjugated 3MT was increased in 30 patients (24%) (P=0.13). Plasma free MN levels were increased in seven patients (6%) and urinary deconjugated MN levels in six patients (5%) (P=1.00). Plasma free normetanephrine (NMN) levels were increased in seven patients (6%), and five patients had increased urinary excretion of deconjugated NMN (4%) (P=0.69). Plasma free combined MN levels (NMN, MN, and 3MT) were increased in 41 patients (33%), whereas 24-h urinary excretion rates of deconjugated combined MNs were increased in 33 patients (27%, P<0.05). CONCLUSIONS: The combined levels of free MNs and free 3MT in plasma indicate a higher number of biochemically active HNPGLs than the 24-h urinary excretion rates of these markers.

Characterization and diagnosis of cancer by native fluorescence spectroscopy of human urine.

Urine is one of the diagnostically important bio fluids, as it has different metabolites in it, where many of them are native fluorophores. Native fluorescence characteristics of human urine samples were studied using excitation-emission matrices (EEMs) over a range of excitation and emission wavelengths, and emission spectra at 405 nm excitation, to discriminate patients with cancer from the normal subjects. The fluorescence spectra of urine samples of cancer patients exhibit considerable spectral differences in both EEMs and emission spectra with respect to normal subjects. Different ratios were calculated using the fluorescence intensity values of the emission spectra and they were used as input variables for a multiple linear discriminant analysis across different groups. The discriminant analysis classifies 94.7% of the original grouped cases and 94.1% of the cross-validated grouped cases correctly. Based on the fluorescence emission characteristics of urine and statistical analysis, it may be concluded that the fluorophores nicotinamide adenine dinucleotide (NADH) and flavins may be considered as metabolomic markers of cancer.

Elevated levels of 1-hydroxypyrene and N'-nitrosonornicotine in smokers with head and neck cancer: A matched control study.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is associated with tobacco use. Still, most smokers do not develop HNSCC. The mechanisms of varying susceptibility to HNSCC are poorly studied to date. Tobacco metabolite research provides insight regarding the innate metabolism and excretion of carcinogens. METHODS: Smokers with HNSCC (cases) were compared with smokers without HNSCC (controls) in a matched cohort. The tobacco metabolites studied were: 1-hydroxypyrene (1-HOP), N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). RESULTS: In 33 subjects, mean 1-HOP was 1.82 pmol/mg creatinine versus 1.08 pmol/mg creatinine (p = .004) and mean NNN was 0.10 pmol/mg creatinine versus 0.04 pmol/mg creatinine (p = .01) in cases and controls, respectively. NNAL did not differ between groups. CONCLUSIONS: Smokers with HNSCC have elevated urinary levels of 1-HOP and total NNN compared with matched controls, suggesting an increased effective exposure to these carcinogens. Tobacco constituent metabolites may be useful in understanding tobacco-related carcinogenesis in HNSCC.

Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine.

AIMS: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. RESULTS: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (rp 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). INNOVATION: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. CONCLUSION: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.

Prognostic significance of serum retinol, serum alpha-tocopherol, and urinary neopterin in patients with head and neck carcinoma treated with external beam radiation.

High serum or urinary neopterin concentrations are associated with poor prognosis in patients with tumors of different primary locations, but reports on neopterin in patients with head and neck carcinoma are relatively less numerous. It has been established that decreased circulating concentrations of retinol and alpha-tocopherol are common in this population. We have evaluated the prognostic significance of urinary neopterin, serum retinol, and alpha-tocopherol in 44 patients with head and neck carcinoma. Urinary neopterin, serum retinol, and alpha-tocopherol were determined with high-performance liquid chromatography. High urinary neopterin and low serum retinol were predictive of poor prognosis, while the prognostic significance of low alpha-tocopherol was of borderline significance. Serum retinol significantly decreased during external beam radiation, but a less marked decrease of alpha-tocopherol during therapy did not reach statistical significance. An increase of urinary neopterin was evident late during the course of treatment. In conclusion, high urinary neopterin and low serum retinol are predictive of poor prognosis in patients with head and neck carcinoma.

Urinary 5-HIAA excretion is not increased in patients with head and neck paragangliomas.

BACKGROUND: Case reports have documented carcinoid-like features in head and neck paragangliomas (HNPGLs), which, in addition to catecholamine storing granules, may also contain granules with serotonin. Serotonin is metabolized to 5-hydroxyindoleacetic acid (5-HIAA). 
 AIM: To assess the urinary excretion rates of 5-HIAA and catecholamines in HNPGL patients.
 METHODS: In 114 consecutive HNPGL patients, normetanephrine, metanephrine, norepinephrine, epinephrine, VMA, dopamine, 3-methoxytyramine and 5-HIAA excretion rates were measured in two 24-hour urinary samples. Increased excretion rates were defined as an increase of the average hormone excretion rate of 2 urine samples above the reference range. In all patients with catecholamine excess, intrathoracic and abdominal paragangliomas were excluded by 123I-MIBG scintigraphy, MRI and/or CT. Genetic screening for mutations in genes of the succinate dehydrogenase (SDH) family was performed. 
 RESULTS: Mean urinary 5-HIAA excretion rate was 14±9 µmol/24 hours (reference range 10-44 µmol/24 hours). Urinary 5-HIAA excretion was slightly increased in only 1 patient (48 µmol/24 hours). None of the 50 patients (44%) with increased urinary excretion rates of catecholamines and/or their metabolites had elevated 5-HIAA excretion.
 CONCLUSION: Urinary 5-HIAA excretion is within the normal reference range in almost all HNPGL patients. Therefore, this parameter has no clinical relevance in the routine clinical assessment of HNPGL patients.

Factors associated with smoking abstinence among smokers and recent-quitters with lung and head and neck cancer.

INTRODUCTION: Smoking cessation among cancer patients is critical for improving outcomes. Understanding factors associated with smoking abstinence after the diagnosis of cancer can provide direction to develop and test interventions to enhance cessation rates. The purpose of this study was to identify determinants of smoking outcomes among cancer patients. METHODS: Standardized questionnaires were used to collect data from 163 smokers or recent-quitters (quit≤6 months) at study entry of which 132 and 121 had data collected at 3 and 6 months. Biochemical verification was conducted with urinary cotinine and carbon monoxide. Descriptive statistics, Cronbach alpha coefficients, Pearson correlations, Fisher's exact test, and multivariable logistic regression were used for analyses. RESULTS: Seven-day-point-prevalence-abstinence (PPA) rates were 90/132 (68%) at 3 months; 46/71 (65%) among lung and 44/61 (72%) among head and neck cancer patients, whereas 7-day-PPA rates were 74/121 (61%) at 6 months; 31/58 (53%) among lung and 43/63 (68%) among head and neck cancer patients. Continuous abstinence rates were 63/89 (71%) at 3 months; 32/45 (71%) among lung and 31/44 (70%) among head and neck cancer patients, whereas continuous abstinence rates were 46/89 (52%) at 6 months; 18/45 (40%) among lung and 28/44 (64%) among head and neck cancer patients. Lower cancer-related, psychological and nicotine withdrawal symptoms were associated with increased 7-D-PPA abstinence rates at 3 and 6 months in univariate models. In multivariable models, however, decreased craving was significantly related with 7-day-PPA at 3 months and decreased craving and increased self-efficacy were associated with 7-D-PPA at 6 months. Decreased craving was the only factor associated with continuous abstinence at 6 months. CONCLUSIONS: Smoking outcomes among lung and head and neck cancer patients appear to have remained the same over the last two decades despite the availability of an increased number of pharmacotherapy options to treat tobacco dependence. Decreased craving and increased self-efficacy were the most consistent factors associated with improved smoking outcomes but symptom control may also play a role in optimal management. Use of combined, and/or higher doses of pharmacotherapy along with behavioral interventions that increase self-efficacy and manage symptoms may promote enhanced cessation rates.

Dopamine excess in patients with head and neck paragangliomas.

AIM: This study aimed to determine the prevalence of excess dopamine in relation to clinical symptoms and nuclear imaging in head and neck paraganglioma (PGL) patients. PATIENTS AND METHODS: Thirty-six consecutive patients with head and neck PGLs, evaluated between 1993 and 2009, were included. Clinical symptoms, dopamine excess (urinary 3-methoxytyramine (3-MT) or dopamine and/or plasma dopamine or 3-MT) and (nor)epinephrine excess (urinary (nor)metanephrine) as well as (111)In-octreotide and (123)I-metaiodobenzylguanide (MIBG) scintigraphy were documented. RESULTS: Dopamine excess was found in seven patients (19.4%), but was unrelated to clinical signs and symptoms. Excretion of other catecholamines was unremarkable, except in one patient with adrenal pheochromocytoma. (123)I-MIBG uptake (present in 36.1% of patients) was associated with dopamine excess (p = 0.03). CONCLUSION: Dopamine excess is present in a considerable percentage of patients with head and neck PGL, and its measurement may be useful in follow-up. Measurement of other catecholamines is necessary to rule out co-existent pheochromocytoma.

Increased urinary excretion of 3-methoxytyramine in patients with head and neck paragangliomas.

CONTEXT: Patients with head-and-neck paragangliomas (HNPGL) are regularly screened for catecholamine excess. The clinical relevance of increased urinary secretion of 3-methoxytyramine is unclear in HNPGL. OBJECTIVE: The aim of the study was to assess the prevalence and the clinical, biochemical, and radiological presentation of patients with HNPGL with increased urinary excretion of 3-methoxytyramine. PATIENTS AND METHODS: A total of 136 consecutive patients with HNPGL were included and screened for catecholamine excess by measurement of 24-h urinary excretion of (nor)metanephrine, (nor)epinephrine, vanillylic mandelic acid, dopamine, and 3-methoxytyramine. In patients with catecholamine excess, abdominal/intrathoracic paragangliomas were excluded by (123)I-metaiodobenzylguanidine scintigraphy, magnetic resonance imaging, and/or computed tomography. RESULTS: Urinary 3-methoxytyramine excretion was increased in 31 of the 136 patients (23%). In 18 of these 31 patients, this was the only sign of biochemical activity of HNPGL. Dopamine excretion was higher in subjects with increased 3-methoxytyramine excretion (1.62 +/- 0.1 micromol/24 h vs. 2.5 +/- 0.3 micromol/24 h; P < 0.01). Of the 136 HNPGL patients, 21 (15%) had excessive excretion of at least one catecholamine and/or their metabolites when 3-methoxytyramine excretion was not taken into account. With the inclusion of patients with excessive 3-methoxytyramine excretion, 39 (29%) had excessive catecholamine excretion. Patients with 3-methoxytyramine excess had significantly more complaints of palpitations (P < 0.01), diaphoresis (P = 0.03), collapse (P < 0.05), and a higher pulse rate (P < 0.01). Increased excretion of 3-methoxytyramine was not associated with particular types of HNPGL or genotypes. CONCLUSIONS: A substantial number of HNPGL patients have biochemically active tumors, reflected in increased excretion of 3-methoxytyramine, associated with increased dopamine excretion. Some patients only display increased excretion of 3-methoxytyramine, but not of other catecholamines or their metabolites.