Urinary 5-hydroxyindoleacetic Acid Levels Research Articles

The Variability of Tryptophan Metabolism in Patients with Mixed Type of Irritable Bowel Syndrome.

Patients with a mixed type of irritable bowel syndrome (IBS-M) experience constipation and diarrhea, which alternate between weeks or months. The pathogenesis of this syndrome is still little understood. The aim of the study was mainly to evaluate the urinary excretion of selected tryptophan (TRP) metabolites during the constipation and diarrhea periods of this syndrome. In 36 patients with IBS-M and 36 healthy people, serum serotonin level was measured by ELISA and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN) and indican (3-IS) were determined using the LC-MS/MS method. The levels of all above metabolites were higher in the patient group, and increased significantly during the diarrheal period of IBS-M. In particular, the changes concerned 5-HIAA (3.67 ± 0.86 vs. 4.59 ± 0.95 mg/gCr, p < 0.001) and 3-IS (80.2 ± 17.4 vs. 93.7 ± 25.1 mg/g/Cr, p < 0.001). These changes coexisted with gut microbiome changes, assessed using hydrogen-methane and ammonia breath tests. In conclusion, the variability of TRP metabolism and the gut microbiome may cause the alternation of IBS-M symptoms.

Impact of Long-Rope Jumping on Monoamine and Attention in Young Adults.

Previous research has shown that rope jumping improves physical health; however, little is known about its impact on brain-derived monoamine neurotransmitters associated with cognitive regulation. To address these gaps in the literature, the present study compared outcomes between 15 healthy participants (mean age, 23.1 years) after a long-rope jumping exercise and a control condition. Long-rope jumping also requires co-operation between people, attention, spatial cognition, and rhythm sensation. Psychological questionnaires were administered to both conditions, and Stroop task performance and monoamine metabolite levels in the saliva and urine were evaluated. Participants performing the exercise exhibited lower anxiety levels than those in the control condition. Saliva analyses showed higher 3-methoxy-4-hydroxyphenylglycol (a norepinephrine metabolite) levels, and urine analyses revealed higher 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid (a serotonin metabolite) levels in the exercise condition than in the control. Importantly, urinary 5-hydroxyindoleacetic acid level correlated with salivary and urinary 3-methoxy-4-hydroxyphenylglycol levels in the exercise condition. Furthermore, cognitive results revealed higher Stroop performance in the exercise condition than in the control condition; this performance correlated with salivary 3-methoxy-4-hydroxyphenylglycol levels. These results indicate an association between increased 3-methoxy-4-hydroxyphenylglycol and attention in long-rope jumping. We suggest that long-rope jumping predicts central norepinephrinergic activation and related attention maintenance.

Treatment with Lanreotide Depot Following Octreotide Long-Acting Release Among Patients with Gastroenteropancreatic Neuroendocrine Tumors.

Objective: To examine patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who receive sequential treatment with somatostatin analogs.Materials and Methods: This retrospective chart review examined lanreotide depot/autogel tolerability and efficacy among GEP-NET patients who received lanreotide after octreotide long-acting release (LAR) at Tufts University Medical Center. Information obtained included background patient characteristics, dosing, adverse events (AEs), radiologic response, and biochemical markers.Results: Patients (n = 16; 43–81 years; mean age, 64.25 years; 11 female) with nonfunctional, low-grade GEP-NETs receiving octreotide LAR 30–60 mg were transitioned to lanreotide because of patient decision (n = 6), disease progression (n = 6), AEs (n = 2), poor tolerance (n = 1), and injection discomfort/pain (n = 1). Lanreotide doses started at 120 mg (n = 13), 90 mg (n = 1), or 60 mg (n = 2); 8 patients received concomitant therapies, mostly liver-directed (radiofrequency ablation/radioembolization). AEs associated with lanreotide experienced by ≥2 patients were fatigue, diarrhea, nausea, hypertension, pancreatic enzyme deficiency, and hyperglycemia. Radiologic treatment responses of the combination of lanreotide with other therapeutic modalities included complete response (n = 1), partial response (n = 5), and stable disease (n = 9). One patient had radiologic progression. Serum serotonin and chromogranin levels decreased, but urinary 5-hydroxyindoleacetic acid levels appeared relatively unchanged.Conclusion: Among post-octreotide GEP-NET patients, including those with disease progression or poor octreotide tolerance, lanreotide alone or with concomitant therapies was well tolerated and associated with radiologic responses.

Prognostic Utility of Total 68Ga-DOTATATE-Avid Tumor Volume in Patients With Neuroendocrine Tumors

Survival times vary among patients with neuroendocrine tumors (NETs) - even among those with the same site, stage, and grade of primary tumor. This makes it difficult to select treatment for patients with unresectable NETs because some patients can survive decades without treatment. 68Gallium-DOTATATE positron emission tomography with computed tomography (68Ga-DOTATATE PET/CT) is a sensitive imaging technique for detection of NETs. We investigated the prognostic accuracy of 68Ga-DOTATATE PET/CT-based analysis of tumor volume in patients with NETs. We performed a prospective study of 184 patients with NETs (128 [69.6%] with metastases and 11 patients [6.0%] with locally advanced disease) at the National Institutes of Health Clinical Center (Bethesda, MD) from 2013 through 2017. All patients underwent 68Ga-DOTATATE PET/CT image analysis and total 68Ga-DOTATATE-Avid tumor volume (68Ga-DOTATATE TV) was determined. We also measured fasting serum chromogranin A, neuron-specific enolase, gastrin, glucagon, vasoactive intestinal peptide, pancreatic polypeptide, and 24-hour urinary 5-hydroxyindoleacetic acid levels in all patients. Disease progression was defined as a new lesion or a growth of a known lesion during the interval between baseline 68Ga-DOTATATE PET/CT scan and follow-up imaging (14.0 ± 6.1 months; range, 1-35 months). The primary outcomes were progression-free survival (PFS) and disease-specific mortality during a median follow-up time of 18 months (range, 4-35 months). We found an inverse correlation between quartiles of 68Ga-DOTATATE TV and PFS (P= .001) and disease-specific survival (P= .002). A 68Ga-DOTATATE TV of 7.0 mL or more was associated with higher odds of disease progression (hazard ratio, 3.0; P= .04). A 68Ga-DOTATATE TV of 35.8 mL or more was associated with increased risk of disease-specific death (hazard ratio, 10.6) in multivariable analysis (P= .01), as well as in subgroup analysis of patients with pancreatic NETs. In a prospective study, we demonstrated the prognostic utility of 68Ga-DOTATATE TV in a large cohort of patients with NETs, in terms of PFS and disease-specific mortality.

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...

58-Year-Old Woman With Melena

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Rochester, MN (T.G.C., B.A.-B.); Advisor to residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (C.G.L.). A 58-year-old woman presented to the emergency department with a 3-day history of passing dark, tarry stools. Her medical history was notable for symptomatic hemophilia A carrier state, gastroesophageal reflux disease, internal hemorrhoids, papillary thyroid cancer treated with thyroidectomy and radioactive iodine for nodal metastasis with secondary hypothyroidism, and obesity with a recent intentional 22.5-kg weight loss. She reported a 3-day history of passing black, tarry stools, averaging 3 stools per day. She did not have light-headedness on standing, any previous episodes, abdominal pain, vomiting, hematochezia, hematemesis, or history of liver or renal disease or alcohol abuse. She was not taking nonsteroidal anti-inflammatory drugs, iron, bismuth subsalicylate, or antiplatelet or anticoagulant medications. Her family history was notable for adenomatous colonic polyposis (at age 17 years, her son was diagnosed as having adenomatous colonic polyps that necessitated a subtotal colectomy). The patient’s last colonoscopy was 4 years before the current presentation and was negative for masses or polyps. On presentation, she had sinus tachycardia at 110 beats/min with a blood pressure of 111/ 51 mmHg. Examination findings were remarkable for conjunctival pallor and positive results on a fecal occult blood test with melenic stool noted on rectal examination. Examination revealed no abdominal tenderness or stigmata of chronic liver disease. Laboratory testing revealed the following notable results (reference ranges provided parenthetically): hemoglobin, 5.5 g/dL (12.015.5 g/dL); platelets, 179 10/L (150450 10/L); international normalized ratio, 1.0 (0.8-1.2); activated partial thromboplastin time, 27 seconds (28-38 seconds); factor VIII activity, 86% (55%-200%); sodium, 139 mmol/L (135-145 mmol/L); potassium, 4.2 mmol/L (3.6-5.2 mmol/L); serum urea nitrogen, 28 mg/dL (6-21 mg/dL); and creatinine, 0.7 mg/dL (0.6-1.1 mg/dL).

Outcome after resection and radiofrequency ablation of liver metastases from small intestinal neuroendocrine tumours

In patients with small intestinal neuroendocrine tumour (SI-NET), liver resection or radiofrequency ablation (RFA) of liver metastases is performed for palliation of carcinoid syndrome, and in an effort to improve survival. Data are generally reported from case series, and no randomized trials have studied these treatments. The aim was to compare outcome after liver resection and/or RFA with that of non-surgical treatment in patients with liver metastases from SI-NET. The study included patients with liver metastases from SI-NET who underwent liver RFA/resection or were treated non-surgically. A propensity score match was performed to reduce bias between groups, using baseline variables such as the Charlson co-morbidity index, age, symptoms, carcinoid heart disease, extent of metastases and proliferation index. Some 103 patients who had RFA and/or liver resection were compared with 273 controls. Propensity score matching resulted in two matched groups, each of 72 patients, with no significant differences in baseline variables. The matched resection/RFA and control groups showed no difference in overall survival (both 74 per cent at 5 years; P = 0·869) or disease-specific survival (74 versus 78 per cent respectively at 5 years; P = 1·000). However, urinary 5-hydroxyindoleacetic acid levels were lower (median 77 versus 120 µmol per 24 h; P = 0·005) and the proportion of patients with progressive disease within the liver was smaller (2 of 18 versus 8 of 18; P < 0·001) in the resection/RFA group after 5 years. These data do not support the use of liver resection and/or RFA in an effort to prolong survival in patients with liver metastases from SI-NET.

Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration.

The management of overweight may include the use of dietary supplements targeted to counter the feeling of hunger. A randomized, double-blind, placebo-controlled trial has been performed in 20 overweight females. These subjects were randomly assigned to supplement their diet with either an extract from Griffonia Simplicifolia (10 subjects) or a placebo (10 matched subjects) for 4-weeks, in conjunction with a personalised reduced calorie diet. The main aim of this study was to evaluate the efficacy, by the assessment of 24-h urinary 5-hydroxyindoleacetic acid levels (5-HIAA), of 1-month administration of a dietary supplement containing 5-hydroxytryptophan (5-HTP) from botanical extracts in healthy, overweight females. Secondary endpoints were the assessment of sensation of appetite (by Haber score), body composition, and severity of binge eating. The supplemented group had a significant increase of 24-h urinary 5-HIAA levels (p<0.001), and a decrease in Haber score (p<0.001) while the placebo group did not show significant changes. With regard to changes in body composition, statistically significant differences between the treatment groups were found for the mean change in BMI, suprailiac skinfold thicknesses, arm circumference and hip circumference. Other parameters were found to be similar in the treated and in the placebo groups. In conclusion, this study shows that the 5-hydroxytryptophan present in the Griffonia extract, administered via spray to the oral cavity, is adequately absorbed, as confirmed by the increase in 24-h urinary 5-HIAA, and that the supplementation of the diet of overweight women with 5-hydroxytryptophan increases the feeling of satiety associated with a decrease in BMI.

The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers

BackgroundSerotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters.MethodsHuman ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining.ResultsOur results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate.ConclusionsIn the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects.

Activin A in Carcinoid Heart Disease: A Possible Role in Diagnosis and Pathogenesis

Background/Aims: Carcinoid heart disease (CHD), a complication of neuroendocrine tumors (NETs), is characterized by right heart fibrotic lesions. Though serotonin is likely involved, the pathogenesis of CHD remains unclear. Cytokines and growth factors with fibrogenic properties may play a role. We sought to examine the relationship between plasma levels of fibrogenic cytokines and growth factors and CHD, both to provide further insight into possible biomarkers of CHD as well as into the possible pathogenesis of CHD. Methods: Plasma samples obtained from 71 patients with NETs and 18 controls were analyzed using enzyme immunoassays. All patients underwent echocardiography. Results: 15 patients (21%) had CHD, all of whom had carcinoid syndrome compared to 82% of those without CHD. CHD patients were older (p = 0.01), had larger (p = 0.007) and more numerous liver metastases (p = 0.04), and had elevated 24-hour urinary 5-hydroxyindoleacetic acid (U-5HIAA) (p = 0.03) and serum chromogranin A levels (p = 0.02). CHD patients had higher plasma levels of C-reactive protein (p = 0.03), osteoprotegerin (p = 0.005), and activin A (p = 0.005) than patients without CHD. A significant direct correlation between activin A and U-5HIAA levels was observed in the total patient group (r = 0.30, p = 0.02). Activin A ≧0.34 ng/ml (odds ratio (OR) 5.35 [1.01; 28.17], p = 0.048) and age ≧69.5 (OR 6.10 [1.60; 23.24], p = 0.008) were independent predictors of CHD. Activin A levels were elevated to the same degree in both early and advanced CHD. Activin A ≧0.34 ng/ml had 87% sensitivity and 57% specificity for detecting CHD (p = 0.006). Conclusion: Elevated plasma activin A levels are associated with the presence of CHD.

Gastroenteropancreatic Neuroendocrine Tumors in Patients With HIV Infection: A Trans-Atlantic Series

BackgroundNon-AIDS–defining cancers are an important problem in HIV-infected patients. The occurrence of neuroendocrine (NE) tumors in sites other than the lung and skin has not been well characterized in the setting of concurrent HIV infection. MethodsHIV-positive patients with biopsy-confirmed NE tumors localized to the gastrointestinal tract were identified based on the personal archives of the authors. A retrospective chart review was performed, and data regarding demographics, HIV status, presenting symptoms and signs, diagnostic work-up, therapeutic interventions, and outcome were extracted. ResultsWe identified 4 adult patients, mean age 42 years (range: 37–47) infected with HIV, who developed NE tumors originating in their gastrointestinal tact. They had only moderate immunosuppression with a median CD4+ count of 497 cells/mm3 (range: 182–1100) and chronic HIV infection (2–15 years duration). Symptoms at presentation were nonspecific, including abdominal pain, diarrhea, weight loss, and rectal bleeding. A specialized diagnostic work-up was required, including serum chromogranin and urinary 5-hydroxyindoleacetic acid levels, colonoscopy, radioactive isotope scans, and the demonstration of NE differentiation in procured pathologic material. The spectrum of tumors ranged from benign (typical carcinoid) to highly aggressive neoplasms (NE carcinoma). Treatment with octreotide, surgical resection, or systemic chemotherapy provided effective symptomatic relief and was associated with a favorable outcome, despite metastases in 2 patients. ConclusionsThese cases serve to broaden the spectrum of neoplasms that may be encountered in the current HIV era, and illustrate the difficulty in establishing the diagnosis of NE tumors in the context of HIV infection.

A prospective clinical trial evaluating urinary 5-hydroxyindoleacetic acid levels in the diagnosis of acute appendicitis

Background To improve the diagnostic accuracy of identifying acute appendicitis, imaging modalities, such as ultrasound and the computed tomography scan, are used in combination with the history and physical examination. There is no reliable single laboratory marker to assist with this diagnosis. During inflammation, enterochromaffin cells in the appendix secrete serotonin, and 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite excreted in urine, has been found to be elevated in patients presenting with acute appendicitis. Objective The aim of this study was to measure the urinary 5-HIAA concentrations of patients presenting with symptoms of acute appendicitis to determine the sensitivity and specificity of urinary 5-HIAA levels for diagnosing acute appendicitis. Methods 5-HIAA was quantitatively measured by high-performance liquid chromatography in the spot urine of 100 healthy individuals, aged 18 to 70 years, who presented to the emergency medicine department with a clinical picture of acute appendicitis. Urine concentration results were correlated to the gold standard of histopathologic reports of removed appendices. The sensitivity, specificity, and their 95% confidence intervals were derived. Results Of the 100 patients presenting with symptoms consistent with acute appendicitis, 72 had appendectomies and 2 had cholecystectomies. The remaining 26 patients were discharged after hospital observation. A total of 64 patients were found to have appendicitis: 52 had acute appendicitis, whereas 12 had perforated and/or gangrenous (nonacute) appendices. The acute appendicitis group had a mean urinary 5-HIAA level of 19.31 μmol/L, slightly lower than the 23.10 μmol/L of the patients with gangrenous/perforated appendicitis. The group without appendicitis had a urinary 5-HIAA value of 17.27 μmol/L. Using the lowest of previously reported cutoffs, we calculated the sensitivity and specificity of this test for acute appendicitis as 63% and 33%, respectively. Conclusion Urinary 5-HIAA level is not a good diagnostic tool for determining acute appendicitis.

Intraoperative Management of Patients with Carcinoid Heart Disease Having Valvular Surgery: A Review of One Hundred Consecutive Cases

Cardiac surgery for carcinoid heart disease is complicated by hemodynamic instability secondary to carcinoid crises, cardiovascular dysfunction, and blood loss. The safety of vasopressors and the benefit of aprotinin during concomitant octreotide administration are uncertain. We reviewed the effects of vasopressors and aprotinin on octreotide administration and mortality by univariate analysis in 100 consecutive cases of cardiac surgery for carcinoid heart disease from 1985 to 2003. Because mortality declines were temporally related to the introduction of aprotinin, bivariate analyses were performed to identify other factors associated with mortality. Carcinoid symptoms and hypotension were treated with octreotide (n = 89) and/or vasopressors (n = 93). Vasopressors were not associated with increased octreotide administration. Patients requiring epinephrine had higher mortality but also had worse preoperative New York Heart Association class, higher urinary 5-hydroxyindoleacetic acid levels, and increased blood transfusion requirements. Aprotinin (n = 54) was associated with decreased blood transfusion requirements, increased octreotide administration, but not mortality. Overall mortality was 13%, declining from 28% between 1985 and 1994 to 6% between 1995 and 2003. Mortality was associated with greater blood transfusion requirements and longer duration of cardiopulmonary bypass. Vasopressors may be used in conjunction with octreotide in carcinoid patients. The increased mortality associated with epinephrine likely reflects selection bias rather than a primary adverse effect. The improved survival over time in carcinoid patients is multifactorial and unrelated to aprotinin administration, suggesting further inhibition of the kallikrein-kinin system has little added benefit for this outcome in the presence of octreotide.

Isolated severe tricuspid regurgitation: The importance of identifying underlying mechanism

An 88-year-old woman presented with right heart failure, history of diarrhoea, abdominal pain, weight lost, dyspnoea over several weeks and a new pan-systolic murmur. Echocardiography showed retracted tricuspid leaflets with incomplete coaptation resulting in severe regurgitation. Subcostal view showed an adjacent hepatic cyst leading to biopsy, which revealed neoplastic neuroendocrine cells. Her 24-hour urinary 5-hydroxyindoleacetic acid level was elevated. The unifying diagnosis was carcinoid syndrome for which she was treated. Echocardiography is an important tool for diagnosis, management and prognosis of carcinoid heart disease.

Primary carcinoid tumor of the testis with teratoma metastatic to the para‐aortic lymph node

A primary testicular carcinoid tumor with teratoma metastasized to the para-aortic lymph node. After inguinal orchiectomy, serum and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) were found to be elevated. Chemotherapy consisting of cisplatin, etoposide and bleomycin was not effective on the metastatic lesions. Retroperitoneal lymphadenectomy normalized the levels of 5-HIAA. The patient is alive without recurrence 25 months after the retroperitoneal lymphadenectomy.

Dermatomyositis and duodenal carcinoid

A 70-year-old female presented with erythematous macular rash over arms, shoulders, trunk and face for 4 months, proximal muscle weakness and dysphagia to liquids for 2 months and ulcers over knuckles and back of thighs for 1 month duration. She had history of recurrent oral ulcers and photosensitivity for 1 year. Examination showed pallor, pedal oedema, blood pressure 160/98 mmHg, heliotrope rash, Gottron’s rash, nail fold infarcts, erythema over the shoulders, arms, neck and back, ulcers over the back of thighs, oral ulcers, left axillary lymphadenopathy, grade II muscle power (inability to lift against gravity) at the shoulder and pelvic girdle muscles and poor gag reflex. Neck holding was poor. The rest of the examination was unremarkable. Investigations revealed hemoglobin 8.4 g/dl, erythrocyte sedimentation rate (ESR) 68 mm, normal platelets, total and differential leucocyte counts, renal functions, skiagram chest and urine examination. Her serum glutamate oxaloacetate transaminase (SGOT), aspartate transaminase (SGPT) and creatine phosphokinase (CPK) (MM), serum protein, albumin, bilirubin, alkaline phosphatase were 131 IU/ml (normal 15–40), 66 IU/ml (normal 13–35) and 174 U/ml (normal 24– 170), 4.7 g/dl, 1.9 g/dl, 0.8 mg/dl and 375 IU/ml (normal 65–306), respectively. Test for antinuclear antibody was negative. Electromyogram showed increased insertional activity, spontaneous high frequency discharges, and polyphasic potentials with low amplitude and short duration in quadriceps and deltoid muscles. Ultrasound of the abdomen showed fatty hepatomegaly. Upper gastrointestinal endoscopy (UGIE) was normal. A diagnosis of dermatomyositis (DM) was made and the patient was started on prednisolone 1 mg/kg per day along with hydroxychloroquine. Over the next 6 months her muscle power normalized, oral ulcers and skin rash disappeared completely and laboratory tests for muscle enzymes (SGOT, SGPT, CPK MM) normalized. Sixteen months after initial presentation she presented to the emergency room in hypotension with recurrent bilious vomiting of 7 days duration. Her muscle power was normal and there were no skin rash and oral ulcers. An UGIE study revealed obstruction in the third part of the duodenum. Contrast-enhanced computerised tomogram revealed a mass in the region of the third part of the duodenum with multiple space-occupying lesions (SOLs) in liver (Fig. 1) and lungs. Fine needle aspiration of the hepatic SOLs revealed malignant tumor of neuroendocrine origin. Excretion of urinary 5-hydroxyindoleacetic acid level was elevated (70 mg/dl). Tests for muscle enzymes (SGOT, SGPT, CPKMM), renal functions and liver functions were normal. During the gastrojejunostomy procedure a mesenteric lymph node was excised which confirmed carcinoid tumor on histopathology. On the 5th postoperative day the patient succumbed to massive upper gastrointestinal bleeding.

Treatment of metastatic carcinoid tumours with octreotide

It was previously reported that treatment of metastatic carcinoid tumours with octreotide resulted in complete histological regression of such tumours in women.1 Previous cases of octreotide-related regression in carcinoid tumour masses were also reported.2-4 Our recent observation of a patient with hepatic metastases and carcinoid syndrome revealed that even though no discernible regression in tumour mass was found, octreotide treatment led to rapid improvement in hepatic function. A 79-year-old man was admitted to our hospital in November 2000, with a one-month history of facial flushing, headache and pressure in his ears. These attacks lasted 1–2 minutes and occurred several times a day. On examination, a purplish-red facial appearance, conjunctival hyperaemia and an enlarged liver were noted. Cardiac auscultation was within normal limits. Laboratory tests indicated hepatocellular damage and hepatic dysfunction (Table 1). He had no history of heavy alcohol consumption. Serological tests were negative for hepatitis A, B and C viruses. MRI of the abdomen revealed multiple metastases in the liver and multiple lymph nodes up to 2 cm in diameter in the para-aortic area. A liver biopsy was not attempted because of the prolonged partial thromboplastin time. His urinary 5-hydroxyindoleacetic acid level was elevated at 1326 μmol/24 h (normal range: 10.4–31.2). Imaging studies with CT and MR showed no evidence of a primary tumour. Because of the severity of the carcinoid symptoms and signs indicating hepatic dysfunction, we decided to treat this patient with a somatostatin analogue. Octreotide 50 μg three times daily was begun. During a two-week follow-up, the carcinoid symptoms markedly improved. In addition, hepatic function tests noticeably improved. A repeat MRI three weeks after the start of treatment showed no evidence of mass regression. This patient is on follow-up and octreotide treatment is continuing at the same dose for 12 months. The urinary 5-hydroxyindoleacetic acid level decreased to 271 μmol/24 h at month 4 of treatment. Abdominal MRI at 6 and 12 months of treatment showed no evidence of regression in hepatic and intra-abdominal lymph node metastases. He remains well and is still free of symptoms. Serial biochemical evaluation showed no evidence of deterioration in liver function. It is well known that somatostatin analogues have antiproliferative and antimitotic actions. The effect on liver function tests in our patient may not be explained by the decrease in tumour bulk, although we cannot exclude radiographically undetectable tumour regression. Somatostatin and analogues may have direct and indirect effects on hepatocytes and non-parenchymal liver cells.5, 6 Growth factors are able to modify hepatocyte proliferation in vivo, i.e. transforming growth factor β-1 produced by non-parenchymal liver cells is able to inhibit hepatocyte proliferation.7 Inhibitory effects of octreotide on the release of paracrine/growth factors from tumour cells might explain the recovery of liver function in the short term. Whatever the cause, octreotide led to symptomatic and functional recovery of metastatic carcinoid syndrome in our patient.

Carcinoid syndrome in the absence of hepatic metastases: correlation of CT and In-111 octreotide imaging

A 49-year-old man was hospitalized for investigation of a 2-year history of flushing and diarrhea. His urinary 5-hydroxyindoleacetic acid level was elevated. CT scanning showed no evidence of hepatic metastases and equivocal masses in the mesentery and right pelvis. In-111 octreotide imaging confirmed focal increased uptake in the midabdomen, right iliac fossa, and lower right pelvis at 24 and 48 hours. At laparotomy, soft tissue masses were resected from the mesentery, lower right pelvis, and small bowel in the right iliac fossa. One of the tumor masses was contained within a Meckel’s diverticulum in the terminal ileum. No liver abnormality was found. All resected masses showed classical carcinoid histologic signs. Symptoms resolved immediately after surgery. FIGURE 1Fig. 1: A CT image at the level of the umbilicus shows an equivocal soft tissue mass within the mesentery. This could easily be mistaken for an unopacified loop of the small bowel.FIGURE 2Fig. 2: A CT image of the pelvis shows a possible soft tissue mass (arrowhead) just medial to the opacified distal right ureter.FIGURE 3Fig. 3: An In-111 octreotide scan at 24 hours shows normal uptake in the liver and spleen. Abnormal uptake is present in the midabdomen, corresponding to the mesenteric soft tissue mass on seen on the CT.FIGURE 4Fig. 4: (A) An In-111 octreotide scan at 24 hours shows additional foci in the right iliac fossa and adjacent to the right superolateral wall of the bladder. (B) A CT scan shows no abnormality of the terminal ileum.

Serotonin-Independent Model of Cisplatin-Induced Emesis in the Ferret

para-Chlorophenylalanine (PCPA, 100–200 mg/kg) was used as a pharmacological tool to characterize the 5-hydroxytryptamine (5-HT) involvement in the emesis occurring 24 hr after the administration of cisplatin (10 mg/kg) in the ferret. PCPA was effective to antagonize the initial 8 hr period of retching and vomiting, but potentiated the emesis that occurred during the remaining 8- to 24-hr observation period. Tissue samples removed from the brainstem at 24 hr post injection of cisplatin alone revealed an elevation of 5-HT, dopamine and homovanillic acid that was antagonized by the injection of PCPA. Cisplatin also induced increases in the urinary levels of 5-hydroxyindoleacetic acid that was similarly antagonized by PCPA. Results are discussed in terms of the relevance of 5-HT to the model of cisplatin (10 mg/kg)-induced emesis in the ferret compared to the problem of acute and delayed emesis in man. The residual or delayed phase of cisplatin-induced emesis may involve a 5-HT-independent mechanism.

Carcinoid tumors: Analysis of prognostic factors and survival in 301 patients from a referral center

Little is known about factors related to prognosis in patients with carcinoid disease. In this study we have tried to identify such factors. We have evaluated 301 consecutive carcinoid patients (256 midgut, 39 foregut and six hindgut) referred during 15 years for medical treatment with respect to tumor distribution, hormone production, prognostic factors and survival. Survival was significantly shorter in midgut carcinoid patients with > or = 5 liver metastases or with high levels of urinary 5-hydroxyindoleacetic acid, plasma chromogranin A or neuropeptide K. By univariate analysis, these variables together with the presence of carcinoid syndrome were related to a higher risk of dying. In multivariate analyses, performed in the 71 patients with full information on all variables, advanced age and plasma chromogranin A > 5000 micrograms/l were independent predictors of overall survival. Poor prognostic factors for midgut carcinoid patients were multiple liver metastases, presence of carcinoid syndrome and high levels of the tumor markers studied. In this study the only independent predictors of bad prognosis in midgut, carcinoid patients were advanced age, which however is inherently related to overall survival, and plasma chromogranin A > 5000 micrograms/l. Thus, chromogranin A may prove to be an important prognostic marker for patients with carcinoid tumors.