Urinary 5-HIAA Research Articles

460P - Elevated levels of 5-HIAA and CgA in patients with PanNETs from the CLARINET Study

Background: While carcinoids frequently synthesize, and secrete serotonin into the circulation, and 5-HIAA is a common biomarker in the carcinoids, measurement of 5-HIAA in non-carcinoid PanNET patients (i.e. no hormone-related symptoms or nonfunctional) is not routinely recommended by international guidelines. The incidence of serotonin-producing PanNETs may be underestimated, with potential impact on clinical outcome when serotonin levels remain elevated. We sought to characterize 5-HIAA and CgA levels in PanNET patients who participated in the large placebo-controlled phase III CLARINET Study. Methods: Evaluable data available for urinary 5-HIAA and serum CgA for patients with PanNET in CLARINET study were analyzed. Urinary 5-HIAA and Serum CgA were assessed at baseline and every 12 weeks thereafter through Week 96. Changes in urinary 5-HIAA and serum CgA levels were calculated using a non-parametric Wilcoxon 2-sample test. Biochemical response for urinary 5-HIAA or serum CgA was defined as baseline >upper limit of normal (ULN, 41.6 µmol/d 5-HIAA; 98.1 µg/L CgA) and ≥50% decrease from baseline or a decrease to a value ≤ULN on study. Results: 91/204 patients in CLARINET had PanNETs. Evaluable data for urinary 5-HIAA and serum CgA concentrations were available in 79 and 88 patients, respectively. A substantial number of patients with PanNET had elevated (>ULN) urinary 5-HIAA levels (21/79; 27%) and/or serum CgA (63/88; 72%). Among the 21 PNET patients with baseline 5-HIAA >ULN, biochemical response was achieved in 85% (11/13) lanreotide-treated patients compared with 63% (5/8) in patients on placebo at the last available value (p = 0.33). Among patients with baseline CgA >ULN, biochemical response was achieved in 66% (19/29) of lanreotide vs. 18% (6/34) of placebo-treated patients (p = 0.0002). Limited sample sizes precluded robust analysis for statistically significant differences in the lanreotide vs. the placebo group among patients with elevated biomarkers at baseline and biochemical response. Conclusions: The percentage of patients with elevated urinary 5-HIAA was unexpected. The concept of PanNET and secretion of serotonin may need to be redefined. The potential of 5-HIAA and CgA as biomarkers of response and follow-up in nonfunctioning PanNET is alluring, but requires further study. Data from additional prospective studies are needed to impact clinical practice guidelines. Clinical trial identification: NCT00353496 Legal entity responsible for the study: Ipsen Biopharmaceuticals Funding: Ipsen Biopharmaceuticals r A.T. Phan: Consultant/Advisor: Ipsen, Novartis; speakers’ bureau: Celgene, Genentech, Eli Lilly, Ipsen, Novartis; research support: Incyte, Ipsen, Lexicon, Novartis, Sanofi. E.M. Wolin: Consultant/Advisor: Celgene, Ipsen, Novartis, Pfizer; research support: Ipsen (Inst), Novartis (Inst), Pfizer (Inst). N. Liyanage: Employee of Ipsen. B. Mirakhur: Employee of Ipsen Biopharmaceuticals. S. Pitman Lowenthal: Employee of Ipsen Biopharmaceuticals. A. Vinik: Const/Advisor: Isis, Merck, Neurometrix, Pamlab, Pfizer; speakers bureau: Merck, Pamlab; research support: BMS, Celgene, Eli Lilly, Medivation, Newlink Genetics, Novartis, Pharmaceutical Research Associates, Polaris, PRA International, Tercica, XBiotech. G.A. Fisher, Jr: Consultant/Advisor: Genentech, Ipsen; research support: BMS, Celgene, Lilly, Ipsen, Medivation, Newlink Genetics, Novartis, Pharmaceutical Research Associates, Polaris, PRA International, Tercica, XBiotech; stock ownership: Seattle Genetics. M. Pavel: Consultant/Advisor: Ipsen, Lexicon, Novartis, Pfizer; research support: Novartis.

Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours.

Serotonin secretion occurs in approximately 1%-4% of patients with a pancreatic neuroendocrine tumour (PNET), but the incidence is not well defined. The aim of this study was to determine the incidence of serotonin secretion with and without carcinoid syndrome and the prognostic value for overall survival (OS). Data were collected from 255 patients with a PNET if 24-hours urinary 5-hydroxyindoleacetic acid excretion (5-HIAA) was assessed. Patients were diagnosed with serotonin secretion if 24-hours urinary 5-HIAA excretion was more than 3× the upper limit of normal (ULN) of 50μmol/24hours during follow-up. The effect of serotonin secretion on OS was estimated with uni- and multivariate analyses using a Cox regression. Two (0.8%) patients were diagnosed with carcinoid syndrome, and another 20 (7.8%) had a serotonin-secreting PNET without symptoms. These patients mostly had ENETS stage IV disease with high chromogranin A (CgA). Serotonin secretion was a negative prognostic factor in univariate analysis (HR 2.2, 95% CI: 1.27-3.81), but in multivariate analysis, only CgA>10× ULN (HR: 1.81, 95% CI: 1.10-2.98) and neuron-specific enolase (NSE) >ULN (HR: 3.51, 95% CI: 2.26-5.46) were predictors for OS. Immunohistochemical staining for serotonin was positive in 28.6% of serotonin-secreting PNETs (one with carcinoid syndrome) and negative in all controls. Carcinoid syndrome is rare in patients with a PNET, but serotonin secretion occurs often. This is a negative prognostic factor for OS, but after correction for CgA and NSE, it is no longer a predictor and probably only a "not-so innocent bystander" in patients with high tumour burden.

Clinical Response Profile of Metastatic/Advanced Pulmonary Neuroendocrine Tumors to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE.

The aims of this study were to perform multiparametric response assessment of metastatic/advanced pulmonary neuroendocrine tumors (NETs) to Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) (clinical, biochemical, molecular/structural imaging, and survival assessment) and to study the relationship between response, mortality, and overall survival with dual-tracer molecular imaging parameters. Twenty-two patients (6 women, 16 men; median age, 44 years; range, 16-72 years) of histopathologically proven pulmonary NETs with metastatic/advanced disease were included and analyzed retrospectively. Lu-DOTATATE PRRT was administered using standardized protocol (150 mCi [5.55 GBq] per cycle, cycles repeated at 12-16 weeks' intervals [range, 1-5 cycles; average, 4 cycles]) with amino acid-based renal protection. Assessment with Tc-HYNIC-TOC (in the initial years of PRRT development, n = 11)/Ga-DOTATATE PET/CT (presently, n = 11) and F-FDG PET/CT (n = 22), symptomatic and biochemical parameters (serum CgA and urinary 5-HIAA levels), and anatomical response using contrast-enhanced CT (after 3 cycles) was part of routine pretreatment and response evaluation. The patients were designated as responders and nonresponders based on predefined response assessment criteria. Kaplan-Meier product-limit method was calculated for overall survival (OS) curve after the first PRRT, and corresponding 95% confidence intervals (95% CIs) were estimated for annual survival at 1, 2, 3, and 4 years. The various prognostic variables were also investigated for association with mortality, OS, and treatment response following PRRT. Of 22 patients, 6 had undergone surgical resection of primary tumors. All patients were symptomatic before start of PRRT. Two patients did not qualify for PRRT, and 1 received single cycle with follow-up less than 3 months, hence excluded from the present analysis. Thus, a total 19 patients were analyzed in our study. Symptomatic response following PRRT was observed in 15 (79%) of 19 patients. Based on predefined 3-scale response evaluation criteria, of 19 patients, 12 patients (63%) were finally characterized as responders, and 7 patients (37%) were overall nonresponder to PRRT. All 7 nonresponders had moderate to intense FDG-avid primary lung lesion (SUVmax >5 in 4 of 7 patients), and 5 had FDG-avid metastatic liver disease (SUVmax >5). Peptide receptor radionuclide therapy was well tolerated in all with no major hematologic and renal toxicity (except for 2 patients showing mild grade I renal and hematologic toxicity in the initial cycles and recovery in subsequent follow-up). Seven (37%) of 19 died at the time of analysis. The observed annual OS rates were as follows: 1 year: 94.7% (95% CI, 68.1%-99.2%), 2 years: 66% (95% CI, 35.5%-84.5%), 3 years: 57.7% (95% CI, 28-78.9%), and 4 years: 38.5% (95% CI, 8.1%-69.5%); median OS was 40 months with 39% (95% CI, 13.1%-64.8%). In conclusion, Lu-DOTATATE PRRT was found safe and well tolerated in receptor-positive pulmonary NET. FDG positivity appeared to forecast aggressive tumor behavior.

Effect of lanreotide depot (LAN) on 5-hydroxyindoleacetic acid (5HIAA) and chromogranin A (CgA) in gastroenteropancreatic neuroendocrine (GEP NET) tumors: Correlation with tumor response and progression-free survival (PFS) from the phase III CLARINET study.

4095 Background: 5HIAA or CgA are biomarkers in some GEP NETs. We present posthoc analyses using prospectively collected urinary 5HIAA and serum CgA data from CLARINET. Methods: Adults with moderately or well differentiated, nonfunctioning (no symptoms of carcinoid syndrome), locally advanced or metastatic GEP NETs were randomized to LAN 120mg or placebo (PBO) every 4 weeks (wks) for 96 wks. Tumor response evaluated centrally (RECIST 1.0) and PFS were assessed by treatment. Biochemical response was defined as baseline > upper limit of normal (ULN, 41.6µmol/d 5HIAA; 98.1µg/L CgA) and ≥50% decrease from baseline to ≤ULN value on study. CgA analyses excluded gastrinoma patients (pts). Results: 48% (82/171) (45LAN; 37PBO) and 66% (129/195) (65LAN, 64PBO) of pts had > ULN baseline 5HIAA and CgA. In those pts with no radiologic progression, significantly greater reductions in 5HIAA (Table) and CgA were observed in LAN vs PBO pts at all assessments (all P< 0.05). PFS was significantly prolonged in LAN 5HIAA responders vs nonresponders (median not reached vs 22.1 months, P= 0.0076) but was not significantly different in PBO 5HIAA responders vs nonresponders. There were no significant differences in PFS by CgA response (responders vs nonresponders) in either LAN or PBO pts. Conclusions: These data suggest that serotonin is secreted by nonfunctioning tumors, but does not reach the threshold required for clinical carcinoid symptoms. Monitoring 5HIAA and CgA may be useful during LAN treatment of nonfunctional GEP NETs. Clinical trial information: NCT00353496. [Table: see text]

Posterior Reversible Encephalopathy Syndrome Due To Carcinoid Crisis Complicating Transarterial Chemoembolization for Metastatic Carcinoid Tumour

Posterior Reversible Encephalopathy Syndrome Due To Carcinoid Crisis Complicating Transarterial Chemoembolization for Metastatic Carcinoid Tumour

Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total 68Ga-DOTATATE-Avid tumor volume measurements.

To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by 68Ga DOTATATE PET/CT imaging. A retrospective analysis of a prospective database of patients with NETs. Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total 68Ga-DOTATATE-avid tumor volume (TV) was analyzed. The analysis included 232 patients. In patients with pancreatic NETs (n = 112), 68Ga-DOTATATE TV correlated with CgA (r = 0.6, P = 0.001, Spearman). In patients with multiple endocrine neoplasia type 1 (n = 39), 68Ga-DOTATATE TV correlated with glucagon (r = 0.5, P = 0.01) and PP levels (r = 0.5, P = 0.049). In patients with von Hippel-Lindau (n = 24), plasma VIP (r = 0.5, P = 0.02) and PP levels (r = 0.7, P < 0.001) correlated with 68Ga-DOTATATE TV. In patients with small intestine NET (SINET, n = 74), 68Ga-DOTATATE TV correlated with CgA (r = 0.5, P = 0.02) and 5-HIAA levels (r = 0.7, P < 0.001), with 5-HIAA ≥8.1 mg/24 h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values (P = 0.001). 68Ga-DOTATATE TV in patients with NET of unknown primary (n = 16) and those with NET of other primary location (n = 30) correlated with 5-HIAA levels (r = 0.8, P = 0.002 and r = 0.7, P = 0.02 respectively). Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.

Prognostic and predictive biomarkers in neuroendocrine tumours.

Neuroendocrine tumours are extremely heterogeneous malignancies. Despite marked heterogeneity in clinical course and prognosis, few biomarkers exist to help predict prognosis and guide treatment. Many tumour-based biomarkers (Ki-67, mitotic count, genetic/epigenetic changes and microRNAs) exist, but only Ki-67 and mitotic count have strong evidence to support their routine use. Blood-based markers are easily repeatable, but currently established biomarkers (chromogranin A and urinary 5-HIAA) are difficult to measure accurately in practice. Structural imaging is used routinely via the TNM system. Functional imaging such as 68Ga-based and FDG PET may become valuable biomarkers with their increasing availability, aided by ongoing quantitative research. Multiple nomograms have been proposed to integrate the above factors, but most have not been prospectively validated and are difficult to use in practice. Further research should aim to establish robust new biomarkers and integrate existing ones to help optimise NET treatment.

Pediatric neuroendocrine carcinoid tumors: Management, pathology, and imaging findings in a pediatric referral center.

While neuroendocrine (carcinoid) tumors are increasingly recognized in the adult population, they are often not suspected in children. Retrospective review of all well-differentiated neuroendocrine (carcinoid) tumors was performed based on pathology reports from a quaternary pediatric medical center between January 2003 and June 2016. Clinical presentations, treatment approaches, imaging findings, and outcomes were reviewed and analyzed. A total of 45 cases of pathology-proven carcinoid tumor were reported with an average age of 14.1 years (range: 7-21 years, SD: 2.8 years). Of these cases, 80% (36) were appendiceal, 11% (5) bronchial, 2% (1) colonic, 2% (1) gastric, 2% (1) enteric, and 2% (1) testicular. Metastases were observed in one (3%) appendiceal, one (100%) enteric, and two (40%) bronchial cases. No recurrence was demonstrated in any appendiceal carcinoid cases. Recurrence was seen in one of three extra-appendiceal gastrointestinal tumors. Tumor site and size significantly correlated with metastases and recurrence. Contrary to recent epidemiological investigations in adults, appendiceal carcinoid tumors remain the most common site for pediatric carcinoid tumors. Appendiceal carcinoid tumors exhibited benign clinical courses without recurrence during short-term follow-up. Extra-appendiceal gastrointestinal carcinoid tumors exhibited much more aggressive behavior with greater metastases and recurrence. Bronchial carcinoid tumors demonstrated good clinical response to resection even in cases with mediastinal lymph node involvement. While increased use of urine 5-HIAA levels and somatostatin receptor-specific imaging might improve detection and guide management of extra-appendiceal carcinoid tumors, longer-term follow-up is needed.

Practical LC-MS/MS Method for 5-Hydroxyindoleacetic Acid in Urine.

Serotonin, an endogenous biogenic amine found in enterochromaffin cells of the gastrointestinal tract, is produced in excess by carcinoid tumors. The primary urinary metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), is used in the diagnosis and management of carcinoid disease. This study describes the development and validation of a dilute-and-shoot LC-MS/MS method for the measurement of 5-HIAA in urine. Samples were prepared by dilution in a 96-well format using an automated liquid handler. Chromatographic isolation of the analyte was achieved using a reversed-phase analytical column. A triple quadrupole mass spectrometer with electrospray ionization in positive mode was used for detection and quantification. Data were acquired by multiple reaction monitoring. Two transitions, quantifier (192.1/146.1) and qualifier (192.1/118.1), were monitored for the analyte and its stable isotope-labeled internal standard [5-hydroxyindole-4,6,7-d3-3-acetic-2,2-d2 acid (5-HIAA-d5)]. Chromatography was designed to elute the analyte outside of major suppression zones. Injection-to-injection time was 4 min. The method was validated for linearity, limit of quantification, accuracy, and imprecision. The analytical measurement range was 0.5-100 mg/L. Coefficients of variation for within-run, between-day, and total imprecision ranged from 0.8% to 5.4%. The method produced accurate 5-HIAA concentrations and correlated well (R = 0.9876) with a comparison HPLC method. Matrix effects were evaluated by post-column infusion of urine samples. An analytical specificity study of endogenous compounds, vitamins, medications, and drugs showed minimal interference. A simple, inexpensive LC-MS/MS method was developed for measurement of 5-HIAA in urine. Results from the assay can be used clinically to assess carcinoid tumors.

Validation Trial of a Novel Marker of Delayed Chemotherapy-induced Emesis

Post hoc analyses of study data suggested that the ratio of substance P to 5-HIAA/creatinine was a novel marker associated with risk of developing delayed chemotherapy-induced emesis. In order to verify this finding, a new clinical trial was conducted to prospectively evaluate the marker in patients receiving chemotherapy of high emetic risk level. Treatment in this study was restricted to two doxorubicin and cyclophosphamide-containing regimens. Prior to chemotherapy, blood and urine samples were collected. Serum substance P and urine 5-HIAA and creatinine (Cr) were measured to calculate patient-specific ratios. The attending oncologist had the option to follow current antiemetic guidelines or the investigators’ recommendation based on the subject’s pretreatment marker ratio.Delayed chemotherapy-induced emesis was the primary symptom monitored.Calculated ratios were ranked highest to lowest using the previously identified value of >70 as the cutoff. Of the 36 patients enrolled in the study, 11 had ratios associated with increased risk of delayed emesis. Mean pretreatment ratios for patients with (+) and without (-) emesis were 74.2 and 48.8, respectively. Although non-parametric analysis indicated the between-emesis group variance was not significantly different, p=0.154, a clear trend was observed with a higher percentage of subjects exhibiting delayed symptoms with ratios >70.

ASAM HIDROKSIINDOLASETIK 5 (5-HIAA) AIR KEMIH DI KANKER KOLOREKTAL

Colorectal cancer, in fact is one of the three most malignant tumour types found in the world. Early detection is recommended to find out the problem and will affect better life expectancy. Various study have been conducted looking for a test that can be easily, non invasive, inexpensive, no special equipment and skills required such as by detecting 5-hidroxyindolacetic acid that can be found in the urine. The aim of this study was to analyze 5-HIAA in the urine of colorectal cancer patients. The study was conducted at the Clinic and Surgical Ward, and Clinical Pathology Laboratory, at Dr. Wahidin Sudirohusodo Hospital in Makassar during the period May–August 2011. The study was conducted on 42 patients and 45 controls ranging from 35−74 years old and 20−52 years old, respectively. The diagnosis is based on the histopathological and most were in stage III of adenocarcinoma profile. Rated of 5-HIAA colorectal cancer the highest is in the value of 4–6 and all normal control had value of 1–3. There is a significant association between 5-HIAA and colorectal cancer, that shown the highest stadium of colorectal cancer, and the highest value of urine 5-HIAA. The ideal cut-off point for screening is two (2) with its sensitivity and specificity values are 100% and 88. 9%, respectively. 5-HIAA urine test can be used as a tumor marker for colorectal cancer in conjunction with other supporting tests. Further study is needed to determine the cut-off point with a various clinical stage.

Clinical Vignettes/Case Reports - Colon.

Case: An 84 year old woman with a history of hypertension presented to an outpatient gastroenterology clinic for work up of watery diarrhea. Her diarrhea started one year prior, described as 5-6 loose daily non-bloody bowel movements with associated cramping. Overtime, it increased in frequency and was associated with fecal incontinence and 25 lb weight loss. Physical exam and basic laboratory testing was unremarkable. Negative work up included: EGD and colonoscopies with biopsies, MR enterography, lactulose breath test, infectious work up including stool cultures and O&P, TSH, urine 5-HIAA, VIP, calcitonin, serum gastrin and fecal elastase. Trials of various medications including rifaximin, loperamide, probiotics as well as dietary changes were ineffective. During a later admission for pneumonia, a CT chest demonstrated an incidental 5x3 cm anterior mediastinal mass suspicious for a thymoma. This prompted further laboratory testing showing undetectable levels of IgA and IgM, and decreased IgG. Given concurrent hypogammaglobulinemia and incidental finding of a suspected thymoma, her symptoms were thought to be from Good's syndrome. IVIG therapy was initiated ultimately leading to resolution of her GI symptoms; however patient refused more definitive therapy with biopsy or resection of her mass. Discussion: Good's Syndrome (GS) is a rare disease process characterized by thymoma with associated hypogammaglobulinemia first described by R.A Good in 1954. The typical presentation is characterized by recurrent infections such as bronchitis, sinusitis or GI tract infections such as giardiasis, CMV colitis or cryptosporidiosis. To our knowledge, there are a limited number of cases of chronic non-infectious diarrhea as a manifestation of GS. Although the mechanism has been debated, chronic diarrhea has been associated with hypogammaglobulinemia in diseases such as common variable immune deficiency as well as X-linked agammglobulinemia. When the initial evaluation of chronic diarrhea is unrevealing, Good's Syndrome may warrant consideration. Testing for hypogammaglobulinemia should be considered first and if present, then imaging studies can be done to evaluate for a thymoma. Early diagnosis and recognition of Good's Syndrome is important since outcomes are often poor due to risk of malnutrition, severe recurrent infections as well as hematologic complications.

Biomarkers of acute appendicitis: systematic review and cost\u2013benefit trade-off analysis

BackgroundAcute appendicitis is the most common surgical emergency and can represent a challenging diagnosis, with a negative appendectomy rate as high as 20 %. This review aimed to evaluate the clinical utility of individual biomarkers in the diagnosis of appendicitis and appraise the quality of these studies.MethodsA systematic review of the literature between January 2000 and September 2015 using of PubMed, OvidMedline, EMBASE and Google Scholar was conducted. Studies in which the diagnostic accuracy, statistical heterogeneity and predictive ability for severity of several biomarkers could be elicited were included. Information regarding costs and process times was retrieved from the regional laboratory. European surgeons blinded to these reviews were independently asked to rank which characteristics of biomarkers were most important in acute appendicitis to inform a cost–benefit trade-off. Sensitivity testing and the QUADAS-2 tool were used to assess the robustness of the analysis and study quality, respectively.ResultsSixty-two studies met the inclusion criteria and were assessed. Traditional biomarkers (such as white cell count) were found to have a moderate diagnostic accuracy (0.75) but lower costs in the diagnosis of acute appendicitis. Conversely, novel markers (pro-calcitonin, IL 6 and urinary 5-HIAA) were found to have high process-related costs including analytical times, but improved diagnostic accuracy. QUADAS-2 analysis revealed significant potential biases in the literature.ConclusionWhen assessing biomarkers, an appreciation of the trade-offs between the costs and benefits of individual biomarkers is needed. Further studies should seek to investigate new biomarkers and address concerns over bias, in order to improve the diagnosis of acute appendicitis.

Limited value for urinary 5-HIAA excretion as prognostic marker in gastrointestinal neuroendocrine tumours.

To determine if urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion is of prognostic value for overall survival (OS) in patients with a gastrointestinal neuroendocrine tumour (NET) and to compare the prognostic value with patient characteristics, ENETS/WHO grading, ENETS TNM staging and biomarkers. Data was collected from patients with a gastrointestinal NET or a NET with gastrointestinal metastases and available 5-HIAA excretion in 24-h urine samples. Laboratory results were stratified for urinary 5-HIAA and chromogranin A (CgA): <2× upper limit of normal (ULN), 2-10× ULN, or >10× ULN. For neuron-specific enolase (NSE), this was the reference range or >1× ULN. OS was compared using Kaplan-Meier and log-rank tests, and hazard ratios were calculated using Cox regression for univariate and multivariate analyses. A total of 371 patients were included, 46.6% female with a mean age of 59.9 years. OS was shortest in patients with urinary 5-HIAA excretion >10× ULN vs reference range (median 83 months vs 141 months, P = 0.002). In univariate analysis, urinary 5-HIAA excretion >10× ULN was a negative predictor (HR 1.62, 95% CI: 1.09-2.39). However, in multivariate analysis, only age (HR 1.04, 95% CI: 1.01-1.08), grade 3 disease (HR 5.09, 95% CI: 2.20-11.79), NSE >1× ULN (HR 2.36, 95% CI: 1.34-4.14) and CgA >10× ULN (HR 3.61, 95% CI: 1.56-8.34) remained as the predictors. Urinary 5-HIAA excretion >10× ULN is a negative predictor for OS. However, when added to other biomarkers and grading, it is no longer a predictor for OS. Therefore, it should only be determined to assess carcinoid syndrome and not for prognostic value.

Does elevated urinary 5-hydroxyindole acetic acid level predict acute appendicitis in children?

BackgroundAcute appendicitis is the most common abdominal surgical emergency in children, and appendectomy is the most frequent acute abdominal operation. Prompt diagnosis and surgical treatment are required to reduce the...

Neuroendocrine Tumor of the Appendix in Children.

Neuroendocrine tumor (NET) of the appendix is the most common gastrointestinal epithelial tumor in children. The utility of serum markers or the indication for hemicolectomy has not been established in children. In 45 children diagnosed with appendiceal NET, 89% NETs were incidentally found following appendectomy performed for suspected acute appendicitis. The median age was 12 years, and 56% patients were female. Postoperative somatostatin scan (n=5), serum chromogranin A (n=4), and urine 5-HIAA (n=9) were all within normal limits. Pathology slides of 35 patients showed mesoappendiceal invasion in 29% patients, and vascular invasion in 6% patients. Seven patients (16%) underwent hemicolectomy for invasion of mesoappendix (n=5), tumor near the resection margin (n=1), and tumor size 1.5 cm with vascular invasion (n=1). Only 2 hemicolectomy specimens showed disease: one in the appendiceal stump and the other as a micrometastasis in a mesenteric lymph node. There were no recurrences and all patients were alive and without evidence of disease at last follow-up. Pediatric appendiceal NET tends to have a benign clinical course with excellent prognosis. In the absence of carcinoid syndrome, postoperative scans and serum biomarkers do not seem to be useful. With completely resected tumors, the indication for hemicolectomy is unclear.

Serotonin and melatonin secretion in postmenopausal women with eating disorders.

Postmenopausal women manifest emotional disorders associated with an increase in appetite. The aim of the study was to assess the serotonin and melatonin secretion and metabolism in postmenopausal women in relation to eating disorders. Sixty postmenopausal women and 30 women without hormonal disturbances were enrolled into the study and divided into three groups: group I (control) - women without menstrual disorders, group II - postmenopausal women without appetite disorders and change in body weight, and group III - postmenopausal women with increased appetite and weight gain. Serum melatonin, serotonin, urinary 6-sulfatoxymelatonin (aMT6s), and 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured. Serum serotonin and melatonin levels in groups II and III were lower compared to group I. Urinary 5-HIAA and aMT6s excretion was lower in overweight women. In group III the correlation between the serum level of serotonin, melatonin, and BMI was negative; a high statistical significance was found between BMI and urinary aMT6s excretion. Melatonin supplementation and use of drugs modulating the serotonin homeostasis together with female hormones have a beneficial effect in complex treatment of disorders of eating in postmenopausal women. (Endokrynol Pol 2016; 67 (3): 299-304).

Spot urinary 5-hydroxyindoleacetic acid is not an ideal diagnostic test for acute appendicitis

Background and purpose of the studyThere is growing evidence to suggest the use of urinary 5-hydroxyindoleacetic acid (5-HIAA) test to help with the diagnosis of appendicitis. The aim of our study was to establish whether urinary 5-HIAA could be used as an effective diagnostic test for acute appendicitis. Design and methodsA prospective double-blinded study was carried out from December 2014 to October 2015. Patients admitted to the emergency surgical ward of a teaching hospital with suspected appendicitis were included in the study. The diagnostic accuracy of the test was measured by receiver operating characteristic curve. ResultsNinety-seven patients were divided into 2 groups: acute appendicitis (n=38) and other diagnosis (n=59). The median value of urinary 5-HIAA was 24.19μmol/L (range, 5.39-138.27) for acute appendicitis vs 18.87μmol/L (range, 2.27-120.59) for other diagnosis group (P=.038). The sensitivity and specificity of urinary 5-HIAA at a cutoff value of 19μmol/L were 71% and 50%, respectively. Receiver operating characteristic analysis showed that the area under curve was 0.64 (confidence interval [CI], 0.513-0.737) for urinary 5-HIAA, which was lower than white blood cell count (0.69; CI, 0.574-0.797), neutrophil count (0.68; CI, 0.565-0.792), and C-reactive protein (0.76; CI, 0.657-0.857). There was no significant difference in the median values of 5-HIAA between different grades of severity of appendicitis (P=.704). ConclusionUrinary 5-HIAA is not an ideal test for the diagnosis of acute appendicitis.

Simultaneous electrochemical determination of dopamine and 5-hydroxyindoleacetic acid in urine using a screen-printed graphite electrode modified with gold nanoparticles.

The authors describe a disposable screen-printed graphite electrode (SPGE) modified with gold nanoparticles (AuNPs). The electrode, designated as AuNPs-SPGE, was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. The AuNPs-SPGE combines the electrochemical features of graphite and the disposability of screen-printed electrodes. It displays excellent electrocatalytic activity towards dopamine (DA) and 5-hydroxyindoleacetic acid (5-HIAA). Two well-defined, sharp, and fully resolved voltammetric peaks (at 525mV for DA and at 415mV for 5-HIAA, both vs. Ag/AgCl) were found. Square wave voltammetry was used to simultaneously determine DA and 5-HIAA in mixtures and in urine. The linear working range extends from 0.1 to 120.0μM for both DA and 5-HIAA, and the limits of detection (based on 3× the baseline noise) are 14.0 and 5.7nM, respectively. The fabrication method for the AuNPs-SPGE is highly reproducible. The performance of the AuNPs-SPGE was evaluated by analyzing spiked human urine, and the recoveries were found to be well over 94.0% for both compounds. These results indicate that the AuNPs-SPGE represents a highly selective and sensitive sensor for simultaneous determination of DA and 5-HIAA in urine. Graphical Abstract Fabrication, characterization and electrochemical behavior of gold nanoparticles modified screen-printed graphite electrode towards dopamine and 5-hydroxyindoleacetic acid in human urine.

Treatment patterns and clinical outcomes of patients with metastatic gastroenteropancreatic neuroendocrine tumors (mGEP-NETs).

331 Background: mGEP-NETs are rare and heterogeneous tumors. Limited data has been published on real world clinical management of these tumors. This study was conducted to understand the treatment patterns and clinical outcomes of patients with mGEP-NETs treated in the community oncology setting. Methods: A retrospective study was conducted using US Oncology’s (USON) iKnowMed electronic health record (EHR) database with supplemental chart review. The first diagnostic record of mGEP-NET in the EHR system was defined as the date of diagnosis of mGEP-NET. Inclusion criteria: ≥ 18 years of age at diagnosis; diagnosis of mGEP-NET between 1/1/2008 to 12/31/2012. Patients in clinical trials or with poorly differentiated tumors were excluded. Results: 229 patients were included with a median age of 64.0 years. Primary tumor site included small bowel (47.6%), pancreas (31.4%), and other (21.0%). Tumor grade was available for 134/229 (58.5%) patients, and the majority was reported as well-differentiated (52.8%). Chromogranin A (CgA) and urinary 5-HIAA were reported for 34.9%, and 32.8% of patients respectively. 37 (16.2%) of patients were under observation only. For those receiving systemic treatment, median time to first systemic treatment after diagnosis was 2.7 weeks, with 75% of patients starting therapy by 9.4 weeks. 120 (52.4%) patients received only somatostatin analogs (SSAs) during the study period, and 72 (31.4%) patients received chemotherapy, and/or targeted therapy. In the 1st line setting (n = 192), 148 (77%) patients received SSAs, 23 (12%) chemotherapy, and 21 (10.9%) targeted therapy. The most common AEs for SSAs were diarrhea (18.2%), abdominal pain (16.9%), and fatigue (13.5%). The median OS from diagnosis was 84.2 months [95%CI 70.9, 108.0 months] for the overall cohort. OS was longer in small bowel NETs than in pancreatic or other NETs (median OS 108.0 vs 69.9 vs 84.2 months, p = 0.017). Conclusions: Most of the patients with mGEP-NETs received systemic treatment soon after diagnosis and referral to USON. The OS and AEs were consistent with other studies. Low reporting of CgA, 5-HIAA, and tumor grade reflected variability of clinical practice in the community setting.