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Deng YZ, Song B. Connection between heart rate variability alterations and cancer in tumor patients. World J Cardiol 2025; 17:102999. [DOI: 10.4330/wjc.v17.i3.102999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/18/2024] [Accepted: 03/05/2025] [Indexed: 03/21/2025] Open
Abstract
BACKGROUND A significant proportion of cancer patients experience autonomic dysfunction, and cancer treatments such as chemotherapy and radiation therapy can exacerbate impairments in the cardiac autonomic nervous system. This study sought to investigate the characteristics of heart rate variability (HRV) in individuals with cancer.
AIM To evaluate the relationship between HRV and cancer patients, providing insights and references for cancer treatment.
METHODS The study included 127 cancer patients with available 24-hour dynamic electrocardiogram data. HRV differences were analyzed using both time domain and frequency domain methods. These findings were then compared to HRV data from reference individuals, sourced from literature that utilized the same HRV computing algorithm.
RESULTS Our findings revealed that cancer patients generally exhibited abnormal HRV compared to the reference group. HRV was found to be correlated with age and clinical type (P < 0.05), but no significant correlation was observed with tumor site or gender (P > 0.05).
CONCLUSION This study indicates that cancer patients have significantly abnormal HRV compared to reference individuals, suggesting the presence of a certain level of cardiac autonomic dysfunction in this patient population.
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Affiliation(s)
- Yu-Zhu Deng
- Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
- Department of Electrocardiogram, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230000, Anhui Province, China
| | - Bing Song
- Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
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Spada GE, Masiero M, Pizzoli SFM, Pravettoni G. Heart Rate Variability Biofeedback in Cancer Patients: A Scoping Review. Behav Sci (Basel) 2022; 12:389. [PMID: 36285958 PMCID: PMC9598295 DOI: 10.3390/bs12100389] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 10/01/2022] [Accepted: 10/04/2022] [Indexed: 12/04/2022] Open
Abstract
Heart Rate Variability (HRV) Biofeedback (BFB) has been shown to improve autonomic balance and wellbeing in chronic diseases. As cardiac variability represents an index of cognitive and emotional regulation, HRV-BFB has been shown to lead to improvements in physiological and psychological adaptability and quality of life. However, knowledge of HRV-BFB in cancer patients is lacking, and available results are diversified according to methods and outcomes. The present paper undertakes a scoping review, exploring the use of HRV-BFB to modulate autonomic balance, cancer symptom management, and quality of life in cancer. This scoping review analyzes empirical evidence considering study designs, BFB methods, and psychophysiological outcomes. Research that focused on HRV-BFB effects in cancer patients was selected (79%). In addition, a systematic review and meta-analysis (31%) focusing on HRV, or BFB in chronic conditions, including cancer, were considered. The studies examined BFB treatment for thyroid, lung, brain or colon cancer, hematologic cancer, and survivors or terminal cancer patients. Retrieved studies reported physiological and psychological indices as primary outcomes: they included HRV values, sleep, pain, fatigue, depression, anxiety, and quality of life. Although the heterogeneity of publications makes it difficult to generalize the effectiveness of HRV-BFB, the training has been proven to improve cancer symptoms and well-being.
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Affiliation(s)
- Gea Elena Spada
- Applied Research Division for Cognitive and Psychological Science, European Institute of Oncology, IRCCS, 20132 Milan, Italy
| | - Marianna Masiero
- Applied Research Division for Cognitive and Psychological Science, European Institute of Oncology, IRCCS, 20132 Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
| | | | - Gabriella Pravettoni
- Applied Research Division for Cognitive and Psychological Science, European Institute of Oncology, IRCCS, 20132 Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
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Buchanan-Hughes A, Pashley A, Feuilly M, Marteau F, Pritchard DM, Singh S. Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review. Neuroendocrinology 2021; 111:1-15. [PMID: 32097914 DOI: 10.1159/000506744] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 02/23/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality. METHODS MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. RESULTS Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3-65% and 3-42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266-1,381 versus 67.5-575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791-2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). CONCLUSIONS Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients.
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Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer? PLoS One 2020; 15:e0237244. [PMID: 32817663 PMCID: PMC7440652 DOI: 10.1371/journal.pone.0237244] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 07/22/2020] [Indexed: 12/24/2022] Open
Abstract
Background Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer. Methods Retrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ≥20ms or RMSSD ≥19ms). Primary endpoints were overall and cancer free survival. Results A total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ≥20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607–1.493), p = 0.829; RMSSD <19ms vs RMSSD ≥19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802–2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ≥20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599–1.592), p = 0.924; RMSSD <19ms vs ≥19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706–2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications. Conclusions Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.
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Shi B, Wang L, Yan C, Chen D, Liu M, Li P. Nonlinear heart rate variability biomarkers for gastric cancer severity: A pilot study. Sci Rep 2019; 9:13833. [PMID: 31554856 PMCID: PMC6761171 DOI: 10.1038/s41598-019-50358-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 09/11/2019] [Indexed: 12/24/2022] Open
Abstract
Identifying prognostic factors by affordable tools is crucial for guiding gastric cancer (GC) treatments especially at earlier stages for timing interventions. The autonomic function that is clinically assessed by heart rate variability (HRV) is involved in tumorigenesis. This pilot study was aimed to examine whether nonlinear indices of HRV can be biomarkers of GC severity. Sixty-one newly-diagnosed GC patients were enrolled. Presurgical serum fibrinogen (FIB), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA199) were examined. Resting electrocardiogram (ECG) of 5-min was collected prior to surgical treatments to enable the HRV analysis. Twelve nonlinear HRV indices covering the irregularity, complexity, asymmetry, and temporal correlation of heartbeat fluctuations were obtained. Increased short-range temporal correlations, decreased asymmetry, and increased irregularity of heartbeat fluctuations were associated with higher FIB level. Increased irregularity and decreased complexity were also associated with higher CEA level. These associations were independent of age, sex, BMI, alcohol consumption, history of diabetes, left ventricular ejection fraction, and anemia. The results support the hypothesis that perturbations in nonlinear dynamical patterns of HRV predict increased GC severity. Replication in larger samples as well as the examination of longitudinal associations of HRV nonlinear features with cancer prognosis/survival are warranted.
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Affiliation(s)
- Bo Shi
- School of Medical Imaging, Bengbu Medical College, Bengbu, Anhui, 233030, China
| | - Lili Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, China
| | - Chang Yan
- School of Control Science and Engineering, Shandong University, Jinan, Shandong, 250061, China
| | - Deli Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, China
| | - Mulin Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, China
| | - Peng Li
- School of Control Science and Engineering, Shandong University, Jinan, Shandong, 250061, China.
- Division of Sleep and Circadian Disorders, Brigham & Women's Hospital, Harvard Medical School, Boston, 02115, MA, USA.
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The Role of the Vagus Nerve in Cancer Prognosis: A Systematic and a Comprehensive Review. JOURNAL OF ONCOLOGY 2018; 2018:1236787. [PMID: 30057605 PMCID: PMC6051067 DOI: 10.1155/2018/1236787] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 06/10/2018] [Indexed: 12/11/2022]
Abstract
This article reviews the role of the vagus nerve in tumor modulation and cancer prognosis. We present a systematic review of 12 epidemiological studies examining the relationship between heart rate variability, the main vagus nerve index, and prognosis in cancer patients (survival and tumor markers). These studies show that initially high vagal nerve activity predicts better cancer prognosis, and, in some studies, independent of confounders such as cancer stage and treatments. Since the design of the epidemiological studies is correlational, any causal relationship between heart rate variability and cancer prognosis cannot be inferred. However, various semi-experimental cohort studies in humans and experimental studies in animals have examined this causal relationship. The second part of this paper presents a comprehensive review including human and animal cohort and experimental studies showing that vagotomy accelerates tumor growth, while vagal nerve activation improves cancer prognosis. Based on all reviewed studies, it is concluded that the evidence supports a protective role of the vagus nerve in cancer and specifically in the metastatic stage.
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Kloter E, Barrueto K, Klein SD, Scholkmann F, Wolf U. Heart Rate Variability as a Prognostic Factor for Cancer Survival - A Systematic Review. Front Physiol 2018; 9:623. [PMID: 29896113 PMCID: PMC5986915 DOI: 10.3389/fphys.2018.00623] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 05/08/2018] [Indexed: 12/11/2022] Open
Abstract
An increasing cancer incidence affecting any age and social class is putting serious strain on populations and health care systems around the world. This systematic literature search aims (i) to examine the correlation of heart rate variability (HRV) and cancer patients' prognosis, (ii) to examine the relationship of HRV and clinicopathological features, and (iii) to compare HRV between different patient groups, and between patient and control groups. We conducted a systematic literature review following the PRISMA Statement. We searched the PubMed and EMBASE databases for publications released by December 2017. The search terms were: "cancer" AND "heart rate variability" AND "human" NOT "animal" NOT "review." A total of 19 studies were finally included in this review. Most publications were high-quality observational studies. The studies showed that higher HRV correlated positively with patients' progression of disease and outcome. Thus, we conclude that individuals with higher HRV and advanced coping mechanisms seem to have a better prognosis in cancer progression. HRV appears to be a useful aspect to access the general health status of cancer patients.
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Affiliation(s)
- Evelyne Kloter
- Institute of Complementary Medicine, University of Bern, Bern, Switzerland
| | - Katja Barrueto
- Institute of Complementary Medicine, University of Bern, Bern, Switzerland
| | - Sabine D Klein
- Institute of Complementary Medicine, University of Bern, Bern, Switzerland
| | - Felix Scholkmann
- Institute of Complementary Medicine, University of Bern, Bern, Switzerland
| | - Ursula Wolf
- Institute of Complementary Medicine, University of Bern, Bern, Switzerland
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Pecceu E, Stebbing B, Martinez Pereira Y, Handel I, Culshaw G, Hodgkiss-Geere H, Lawrence J. Vasovagal tonus index (VVTI) as an indirect assessment of remission status in canine multicentric lymphoma undergoing multi-drug chemotherapy. Vet Res Commun 2017; 41:249-256. [PMID: 28791606 PMCID: PMC5694533 DOI: 10.1007/s11259-017-9695-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Accepted: 07/21/2017] [Indexed: 12/19/2022]
Abstract
Vasovagal tonus index (VVTI) is an indirect measure of heart rate variability and may serve as a marker of disease severity. Higher heart rate variability has predicted lower tumour burden and improved survival in humans with various tumour types. The purpose of this pilot study was to evaluate VVTI as a biomarker of remission status in canine lymphoma. The primary hypothesis was that VVTI would be increased in dogs in remission compared to dogs out of remission. Twenty-seven dogs were prospectively enrolled if they had a diagnosis of intermediate to high-grade lymphoma and underwent multidrug chemotherapy. Serial electrocardiogram data were collected under standard conditions and relationships between VVTI, remission status and other clinical variables were evaluated. VVTI from dogs in remission (partial or complete) did not differ from dogs with fulminant lymphoma (naive or at time of relapse). Dogs in partial remission had higher VVTI than dogs in complete remission (p = 0.021). Higher baseline VVTI was associated with higher subsequent scores (p < 0.001). VVTI also correlated with anxiety level (p = 0.03). Based on this pilot study, VVTI did not hold any obvious promise as a useful clinical biomarker of remission status. Further investigation may better elucidate the clinical and prognostic utility of VVTI in dogs with lymphoma.
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Affiliation(s)
- Evi Pecceu
- Royal (Dick) School of Veterinary Studies & Roslin Institute, University of Edinburgh, Roslin, EH25 9RG, UK.
| | - Brittainy Stebbing
- Royal (Dick) School of Veterinary Studies & Roslin Institute, University of Edinburgh, Roslin, EH25 9RG, UK
| | - Yolanda Martinez Pereira
- Royal (Dick) School of Veterinary Studies & Roslin Institute, University of Edinburgh, Roslin, EH25 9RG, UK
| | - Ian Handel
- Royal (Dick) School of Veterinary Studies & Roslin Institute, University of Edinburgh, Roslin, EH25 9RG, UK
| | - Geoff Culshaw
- Royal (Dick) School of Veterinary Studies & Roslin Institute, University of Edinburgh, Roslin, EH25 9RG, UK
| | - Hannah Hodgkiss-Geere
- Royal (Dick) School of Veterinary Studies & Roslin Institute, University of Edinburgh, Roslin, EH25 9RG, UK.,Small Animal Teaching Hospital, University of Liverpool, Liverpool, CH64 7TE, UK
| | - Jessica Lawrence
- Royal (Dick) School of Veterinary Studies & Roslin Institute, University of Edinburgh, Roslin, EH25 9RG, UK.,College of Veterinary Medicine, University of Minnesota, St Paul, MN, 55108, USA
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Abstract
INTRODUCTION Previous studies have shown that autonomic dysfunction is associated with shorter survival in patients with advanced cancer. We examined the association between heart rate variability, a measure of autonomic function, and survival in a large cohort of patients with cancer. METHODS We retrospectively examined the records of 651 patients with cancer who had undergone ambulatory electrocardiogram monitoring for 20 to 24 hours. Time domain heart rate variability (SD of normal-to-normal beat interval [SDNN]) was calculated using power spectral analysis. Survival data were compared between patients with SDNN ≥ 70 milliseconds (Group 1, n = 520) and SDNN < 70 milliseconds (Group 2, n = 131). RESULTS Two groups were similar in most variables, except that patients in group 2 had a significantly higher percentage of male patients (P = 0.03), hematological malignancies (P = 0.04), and use of non-selective serotonin reuptake inhibitor antidepressants (P = 0.04). Patients in group 2 had a significantly shorter survival rate (25% of patients in group 2 died by 18.7 weeks vs. 78.9 weeks in group 1 patients; P < 0.0001). Multivariate analysis showed that SDNN < 70 milliseconds remained significant for survival (hazard ratio 1.9 [95% confidence interval: 1.4-2.5]) independent of age, cancer stage, and performance status. CONCLUSION The presence of cancer in combination with decreased heart rate variability (SDNN < 70 milliseconds) is associated with shorter survival time.
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De Couck M, Gidron Y. Norms of vagal nerve activity, indexed by Heart Rate Variability, in cancer patients. Cancer Epidemiol 2013; 37:737-41. [DOI: 10.1016/j.canep.2013.04.016] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Revised: 04/25/2013] [Accepted: 04/29/2013] [Indexed: 01/22/2023]
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DE COUCK MARIJKE, VAN BRUMMELEN DAVID, SCHALLIER DENIS, DE GRÈVE JACQUES, GIDRON YORI. The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients. Oncol Rep 2013; 30:2435-41. [DOI: 10.3892/or.2013.2725] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 01/07/2013] [Indexed: 11/06/2022] Open
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Mouton C, Ronson A, Razavi D, Delhaye F, Kupper N, Paesmans M, Moreau M, Nogaret JM, Hendlisz A, Gidron Y. The relationship between heart rate variability and time-course of carcinoembryonic antigen in colorectal cancer. Auton Neurosci 2012; 166:96-9. [DOI: 10.1016/j.autneu.2011.10.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2011] [Revised: 09/12/2011] [Accepted: 10/11/2011] [Indexed: 01/17/2023]
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Langer C, Piper C, Vogt J, Heintze J, Butz T, Lindner O, Burchert W, Kersting C, Horstkotte D. Atrial fibrillation in carcinoid heart disease: The role of serotonin. A review of the literature. Clin Res Cardiol 2006; 96:114-8. [PMID: 17115326 DOI: 10.1007/s00392-006-0463-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2005] [Accepted: 09/29/2006] [Indexed: 11/25/2022]
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de Herder WW. Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome). Best Pract Res Clin Gastroenterol 2005; 19:705-15. [PMID: 16253895 DOI: 10.1016/j.bpg.2005.05.007] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
(Neuro-)endocrine tumours of the gastrointestinal tract are also called 'carcinoids'. (Neuro-)endocrine midgut tumours can be categorized according to their clinical behaviour. Most tumours are non-functioning. Functioning tumours are responsible for the carcinoid syndrome. The carcinoid syndrome is almost uniquely associated with midgut carcinoids. Symptoms of the carcinoid syndrome are caused by an excess of biogenic amines, peptides and other factors in the circulation. The typical symptoms of the carcinoid syndrome are diarrhoea, flushing, and carcinoid heart disease. Carcinoid heart disease involves the tricuspid and pulmonary valves and the endocardium. Serum chromogranin A and urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) are biochemical markers. Carcinoid tumours express large numbers of high-affinity somatostatin receptors. These can bind the currently available octapeptide somatostatin analogues. In inoperable patients, biotherapy with somatostatin analogues and interferon-alpha is the treatment of choice. Somatostatin analogues and interferon-alpha significantly improve symptoms.
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Affiliation(s)
- W W de Herder
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
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van der Horst-Schrivers ANA, Wymenga ANM, Links TP, Willemse PHB, Kema IP, de Vries EGE. Complications of midgut carcinoid tumors and carcinoid syndrome. Neuroendocrinology 2004; 80 Suppl 1:28-32. [PMID: 15477713 DOI: 10.1159/000080737] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The carcinoid syndrome, associated with carcinoid tumors of the midgut, consists of symptoms such as diarrhea, flushing, wheezing and cardiovascular symptoms. This review focuses on these symptoms and discusses therapeutic options. The symptoms are caused by the secretion of biogenic amines, polypeptides and other factors of which serotonin is the most prominent. However, diarrhea is also due to factors such as malabsorption. Besides antitumor therapy, more specific interventions such as serotonin receptor blockers can be useful. The carcinoid heart disease involves the tricuspid and pulmonary valve. In the pathogenesis, serotonin plays a central role. The therapeutic approach is mostly symptomatic. Other cardiovascular complications include bowel ischemia and hypertension. Pellagra and psychiatric symptoms are due to a depletion of tryptophan, which is consumed by the carcinoid tumor for serotonin synthesis. Finally, follow-up and clinical practice of patients with carcinoid tumors are discussed.
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Meijer WG, Copray SCVM, Hollema H, Kema IP, Zwart N, Mantingh-Otter I, Links TP, Willemse PHB, de Vries EGE. Catecholamine-synthesizing enzymes in carcinoid tumors and pheochromocytomas. Clin Chem 2003; 49:586-93. [PMID: 12651811 DOI: 10.1373/49.4.586] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Serotonin is the principal endocrine product of carcinoid tumors, but simultaneously increased production of catecholamines has been described in these tumors. As it is not clear whether these tumors contain specific enzymes for catecholamine synthesis, we aimed to detect catecholamine-synthesizing enzymes [tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT)] in midgut carcinoid tumors and pheochromocytoma and to correlate enzyme expression to serotonin production as well as catecholamines and metabolites excreted in urine. METHODS Paraffin-embedded tumor specimens from 21 midgut carcinoid patients and 20 pheochromocytoma patients (10 sporadic and 10 MEN type IIa-related tumors) were stained for TH, DBH, and PNMT, using a three-step biotin-avidin-peroxidase method. RESULTS TH was demonstrated in 9 (43%) of 21 carcinoids and in all (100%) of 20 pheochromocytomas, DBH in 8 (38%) carcinoids and in 15 (75%) pheochromocytomas, and PNMT in 7 (33%) carcinoids and in 13 (65%) pheochromocytomas. Increased urinary excretion of catecholamines and metabolites was observed in 10 (48%) carcinoid patients and in all pheochromocytoma patients. No clinically relevant association between enzyme expression and urinary excretion of catecholamines and metabolites was found. CONCLUSIONS Catecholamine-synthesizing enzymes are present in many carcinoid tumors. This finding possibly indicates the existence of a catecholamine-synthesizing pathway in carcinoids similar to that found in pheochromocytoma.
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Affiliation(s)
- Wim G Meijer
- Department of Medical Oncology, University Hospital Groningen, The Netherlands
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