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Bhatt A, Mishra S, Glehen O. Histopathological Evaluation and Molecular Diagnostic Tests for Peritoneal Metastases with Unknown Primary Site-a Review. Indian J Surg Oncol 2023; 14:15-29. [PMID: 37359927 PMCID: PMC10284789 DOI: 10.1007/s13193-022-01612-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 07/26/2022] [Indexed: 11/25/2022] Open
Abstract
Cancer of unknown primary (CUP) is a well-studied entity with guidelines available for the management of patients with CUP. The peritoneum represents one of the metastatic sites in CUP, and peritoneal metastases (PM) could present as CUP. PM of unknown origin remains a poorly studied clinical entity. There is only one series of 15 cases, one population-based study, and few other case reports on this subject. Studies on CUP, in general, cover some common tumour histological types like adenocarcinomas and squamous carcinomas. Some of these tumours may have a good prognosis though majority have high-grade disease with a poor long-term outcome. Some of the histological tumour types commonly seen in the clinical scenario of PM like mucinous carcinoma have not been studied. In this review, we divide PM into five histological types-adenocarcinomas, serous carcinomas, mucinous carcinomas, sarcomas and other rare varieties. We provide algorithms to identify the primary tumour site using immunohistochemistry when imaging, and endoscopy fails to establish the primary tumour site. The role of molecular diagnostic tests for PM or unknown origin is also discussed. Current literature on site-specific systemic therapy based on gene expression profiling does not show a clear benefit of this approach over empirical systemic therapies.
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Affiliation(s)
- Aditi Bhatt
- Dept. of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad 380054 India
| | - Suniti Mishra
- Dept. of Pathology, Sparsh Hospital, Bangalore, India
| | - Olivier Glehen
- Dept. of Surgical Oncology, Centre Hospitalier Lyon-Sud, Lyon, France
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Konsek-Komorowska SJ, Pęczkowska M, Kolasińska-Ćwikła AD, Cichocki A, Konka M, Roszkowska-Purska K, Ćwikła JB. Analysis of Patients with NET G1/G2 Neuroendocrine Tumors of the Small Intestine in the Course of Carcinoid Heart Disease-A Retrospective Study. J Clin Med 2023; 12:jcm12030790. [PMID: 36769439 PMCID: PMC9918269 DOI: 10.3390/jcm12030790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Neuroendocrine neoplasms of the small intestine (SI-NENs) are one of the most commonly recognized gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Carcinoid heart disease (CHD) is the primary cause of death in patients with the carcinoid syndrome (CS). The aim of this retrospective study was to evaluate possible factors impacting upon overall survival (OS) in subjects with both neuroendocrine tumors (NETs) G1/G2 of the small intestine (SI-NET) and CHD. Enrolled in our study of 275 patients with confirmed G1/G2 SI-NET, were 28 (10%) individuals with CHD. Overall survival was assessed using the Kaplan-Meier method. The Cox-Mantel test was used to determine how OS varied between groups. A Cox proportional hazards model was used to conduct univariate analyses of predictive factors for OS and estimate hazard ratios (HRs). Of the 28 individuals with confirmed carcinoid heart disease, 12 (43%) were found to have NET G1 and 16 (57%) were found to have NET G2. Univariate analysis revealed that subjects with CHD and without resection of the primary tumor had a lower OS. Our retrospective study observed that patients who presented with CHD and without resection of primary tumor had worse prognosis of survival. These results suggest that primary tumors may need to be removed when feasible, but further research is needed. However, no solid recommendations can be issued on the basis of our single retrospective study.
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Affiliation(s)
- Sonia J. Konsek-Komorowska
- Department of Cardiology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
- Correspondence:
| | - Mariola Pęczkowska
- The Cardinal Stefan Wyszyński National Institute of Cardiology, 04-628 Warsaw, Poland
| | | | - Andrzej Cichocki
- The Maria Sklodowska-Curie National Research Institute of Oncology, 02-034 Warsaw, Poland
| | - Marek Konka
- The Cardinal Stefan Wyszyński National Institute of Cardiology, 04-628 Warsaw, Poland
| | | | - Jarosław B. Ćwikła
- Department of Cardiology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
- Diagnostic and Therapeutic Center–Gammed, 02-351 Warsaw, Poland
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Abstract
Carcinoid syndrome, a paraneoplastic condition linked with the release of multiple humoral factors, affects around 30-40% of patients with well-differentiated neuroendocrine tumours. Carcinoid syndrome has a major and unfavourable impact on patients' quality of life; it raises costs when compared to non-functioning neuroendocrine tumours; and it causes patients' lifestyles to alter, such as food, job, physical activity, and social life. Somatostatin analogues have been the first-line therapy for individuals with neuroendocrine tumours and carcinoid disease for decades. While these drugs give considerable relief from carcinoid syndrome symptoms, clinical progression is unavoidable, necessitating further research into newer treatment measures. Carcinoid tumours are sometimes difficult to diagnose because of their vague or nonspecific symptoms. There have been several advancements in all aspects of carcinoid syndrome, as well as novel therapeutics, in the previous few years. New epidemiological studies show that it is becoming more common; increasing insights into the pathogenesis of its various clinical manifestations and its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history, and management of the disease. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till November 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Recent advances", "Carcinoid syndrome", "Neuroendocrine Neoplasms" and "Carcinoid heart disease". We comprehensively reviewed the literature on the pathogenesis, clinical features, and newer treatment modalities for Carcinoid Syndrome. Recent advancements in research and management have resulted from advances in our understanding of the aetiology of carcinoid syndrome. The development of molecular indicators of aggressiveness improved serum tumour markers, and the molecular aetiology of carcinoid heart disease are all possible because of advances in molecular biology. We conducted a comprehensive review to update knowledge regarding the pathophysiology, diagnostic protocols, and current and newer treatments for carcinoid syndrome, which presently requires a multidisciplinary approach, due to the complexity of the illness's aetiology, diagnosis, and therapy.
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Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome. JOURNAL OF ONCOLOGY 2020; 2020:8341426. [PMID: 32322270 PMCID: PMC7160731 DOI: 10.1155/2020/8341426] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 12/07/2019] [Accepted: 12/26/2019] [Indexed: 12/23/2022]
Abstract
Carcinoid syndrome (CS) develops in patients with hormone-producing neuroendocrine neoplasms (NENs) when hormones reach a significant level in the systemic circulation. The classical symptoms of carcinoid syndrome are flushing, diarrhoea, abdominal pain, and wheezing. Neuroendocrine neoplasms can produce multiple hormones: 5-hydroxytryptamine (serotonin) is the most well-known one, but histamine, catecholamines, and brady/tachykinins are also released. Serotonin overproduction can lead to symptoms and also stimulates fibrosis formation which can result in development of carcinoid syndrome-associated complications such as carcinoid heart disease (CaHD) and mesenteric fibrosis. Transforming growth factor beta (TGF-β) is one of the main factors in developing fibrosis, but platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF2), and connective tissue growth factor (CTGF or CCN2) are also related to fibrosis development. Treatment of CS focuses on reducing serotonin levels with somatostatin analogues (SSA's). Telotristat ethyl and peptide receptor radionuclide therapy (PRRT) have recently become available for patients with symptoms despite being established on SSA's. Screening for CaHD is advised, and early intervention prolongs survival. Mesenteric fibrosis is often present and associated with poorer survival, but the role for prophylactic surgery of this is unclear. Depression, anxiety, and cognitive impairment are frequently present symptoms in patients with CS but not always part of their care plan. The role of antidepressants, mainly SSRIs, is debatable, but recent retrospective studies show evidence for safe use in patients with CS. Carcinoid crisis is a life-threatening complication of CS which can appear spontaneously but mostly described during surgery, anaesthesia, chemotherapy, PRRT, and radiological procedures and may be prevented by octreotide administration.
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Agha AM, Lopez-Mattei J, Donisan T, Balanescu D, Iliescu CA, Banchs J, Kim PY, Palaskas NL, Yusuf S, Gladish G, Hassan S. Multimodality imaging in carcinoid heart disease. Open Heart 2019; 6:e001060. [PMID: 31245014 PMCID: PMC6560671 DOI: 10.1136/openhrt-2019-001060] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 04/08/2019] [Accepted: 04/14/2019] [Indexed: 01/05/2023] Open
Abstract
Neuroendocrine neoplasms arise from the gastrointestinal tract and can lead to carcinoid syndrome. Carcinoid heart disease affects more than half of these patients and is the initial presentation of carcinoid syndrome in up to 20 % of patients. Carcinoid heart disease typically leads to valve dysfunction, but in rare instances, carcinoid tumours can also metastasise to the endocardium and myocardium. Cardiovascular imaging plays an integral role in the diagnosis and prognosis of carcinoid heart disease. The use of multimodality imaging techniques including echocardiography, cardiac MRI, cardiovascular CT and positron emission tomography have allowed for a more comprehensive assessment of carcinoid heart disease. In this review, we discuss the features of carcinoid heart disease observed on multimodality imaging, indications for obtaining imaging studies and their role in carcinoid heart disease management.
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Affiliation(s)
- Ali M Agha
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Juan Lopez-Mattei
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.,Department of Diagnostic Radiology, Division of Diagnostic Imaging, he University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Teodora Donisan
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Dinu Balanescu
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Cezar A Iliescu
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jose Banchs
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Peter Y Kim
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Nicolas L Palaskas
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Syed Yusuf
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Greg Gladish
- Department of Diagnostic Radiology, Division of Diagnostic Imaging, he University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Saamir Hassan
- Department of Cardiology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Clement DSVM, Tesselaar MET, van Leerdam ME, Srirajaskanthan R, Ramage JK. Nutritional and vitamin status in patients with neuroendocrine neoplasms. World J Gastroenterol 2019; 25:1171-1184. [PMID: 30886501 PMCID: PMC6421241 DOI: 10.3748/wjg.v25.i10.1171] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/13/2019] [Accepted: 02/22/2019] [Indexed: 02/06/2023] Open
Abstract
Symptoms of gastroenteropancreatic located neuroendocrine neoplasms (GEP-NENs) are often related to food intake and manifest as abdominal pain or diarrhoea which can influence patients nutritional status. Malnutrition is common in cancer patients and influences quality of life, treatment options and survival but is also present in up to 40% of patients with GEP-NENs. As part of malnutrition there are often deficiencies in fat-soluble vitamins, mainly vitamin D. Little knowledge exists on trace elements. Several factors influence the development of malnutrition such as size and localisation of the primary tumour as well as metastases, side effects from treatment but also hormone production of the tumour itself. One of the main influencing factors leading to malnutrition is diarrhoea which leads to dehydration and electrolyte disturbances. Treatment of diarrhoea should be guided by its cause. Screening for malnutrition should be part of routine care in every GEP-NEN patient. Multidisciplinary treatment including dietician support is necessary for all malnourished patients with GEP-NENs.
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Affiliation(s)
- Dominique SVM Clement
- Neuroendocrine Tumour Unit, King’s College Hospital ENETS Centre of Excellence, London SE5 9RS, United Kingdom
| | - Margot ET Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute ENETS Centre of Excellence, Amsterdam 1066 CX, Netherlands
| | - Monique E van Leerdam
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Rajaventhan Srirajaskanthan
- Neuroendocrine Tumour Unit, King’s College Hospital ENETS Centre of Excellence, London SE5 9RS, United Kingdom
- Department of Gastroenterology, King’s College Hospital, London SE5 9RS, United Kingdom
| | - John K Ramage
- Neuroendocrine Tumour Unit, King’s College Hospital ENETS Centre of Excellence, London SE5 9RS, United Kingdom
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Bhatt A, Seshadri RA. Rare Indications for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. MANAGEMENT OF PERITONEAL METASTASES- CYTOREDUCTIVE SURGERY, HIPEC AND BEYOND 2018:369-432. [DOI: 10.1007/978-981-10-7053-2_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Alawneh A, Tuqan W, Innabi A, Abu-Sheikha A, Al-Arja G, Shehadeh I. Successful Palliation of Octreotide-Resistant Diarrhea Using Glycopyrrolate in a Patient With Medullary Thyroid Cancer: A Case Report. J Pain Symptom Manage 2015; 50:e4-6. [PMID: 26100046 DOI: 10.1016/j.jpainsymman.2015.04.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Accepted: 04/05/2015] [Indexed: 11/20/2022]
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Wang YH, Lin Y, Xue L, Wang JH, Chen MH, Chen J. Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995-2012) in South China. BMC Endocr Disord 2012. [PMID: 23194346 DOI: 10.1186/1472 -6823-12-30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
UNLABELLED BACKGROUND Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65-75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. METHODS Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. RESULTS Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. CONCLUSIONS Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.
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Affiliation(s)
- Yu-Hong Wang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People's Republic of China.
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Wang YH, Lin Y, Xue L, Wang JH, Chen MH, Chen J. Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995-2012) in South China. BMC Endocr Disord 2012; 12:30. [PMID: 23194346 PMCID: PMC3526557 DOI: 10.1186/1472-6823-12-30] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Accepted: 11/26/2012] [Indexed: 02/08/2023] Open
Abstract
UNLABELLED BACKGROUND Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65-75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. METHODS Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. RESULTS Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. CONCLUSIONS Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.
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Affiliation(s)
- Yu-hong Wang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People’s Republic of China
| | - Yuan Lin
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People’s Republic of China
| | - Ling Xue
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People’s Republic of China
| | - Jin-hui Wang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People’s Republic of China
| | - Min-hu Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People’s Republic of China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, People’s Republic of China
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Combining anatomic and molecularly targeted imaging in the diagnosis and surveillance of embryonal tumors of the nervous and endocrine systems in children. Cancer Metastasis Rev 2008; 27:665-77. [PMID: 18581060 DOI: 10.1007/s10555-008-9153-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Combining anatomical and functional imaging can improve sensitivity and accuracy of tumor diagnosis and surveillance of pediatric malignancies. MRI is the state-of-the-art modality for demonstrating the anatomical location of brain tumors with contrast enhancement adding additional information regarding whether the tumor is neuronal or glial. Addition of SPECT imaging using a peptide that targets the somatostatin receptor (Octreoscan) can now differentiate medulloblastoma from a cerebellar pilocytic astrocytoma. Combined MRI and Octreoscan is now the most sensitive and accurate imaging modality for differentiating recurrent medulloblastoma from scar tissue. CT is the most common imaging modality for demonstrating the anatomical location of tumors in the chest and abdomen. Addition of SPECT imaging with either MIBG or Octreoscan has been shown to add important diagnostic information on the nature of tumors in chest and abdomen and is often more sensitive than CT for identification of metastatic lesions in bone or liver. Combined anatomical and functional imaging is particularly helpful in neuroblastoma and in neuroendocrine tumors such as gastrinoma and carcinoid. Functional imaging with MIBG and Octreoscan is predictive of response to molecularly targeted therapy with 131I-MIBG and 90Y-DOTA-tyr3-Octreotide. Dosimetry using combined anatomical and functional imaging is being developed for patient-specific dosing of targeted radiotherapy and as an extremely sensitive monitor of response to therapy. Both MIBG and Octreotide are now being adapted to PET imaging which will greatly improve the utility of PET in medulloblastoma as well as increase the sensitivity for detection of metastatic lesions in neuroblastoma and neuroendocrine tumors.
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Abstract
Midgut carcinoids developing in the small intestine represent the most common cause of the carcinoid syndrome, with severe symptoms of flush, diarrhoea, and fibrotic valvular heart disease. The tumours may be histologically identified with specific chromogranin A or synaptophysine immunostainings, and by serotonin reactivity, which supports a midgut origin. Urinary 5-HIAA excretion and serum chromogranin A measurements are used as biochemical tumour markers for clinical diagnosis, and as important monitors of treatment effects and prognostic predictors. The midgut carcinoids have typically slow proliferation and extended disease course, and surgical treatment has become increasingly important for their management. Surgery should aim to remove primary tumours and mesenteric metastases, which may cause long-term abdominal complications, by typical fibrotic intestinal entrapment and small bowel ischaemia due to encasement of mesenteric vessels. Attempts should also be made to surgically remove or ablate liver metastases, since this may significantly contribute to palliation of the carcinoid syndrome. In patients with this syndrome surgery is combined with continuous biotherapy with long-acting somatostatin analogues and interferon, which may alleviate symptoms and cause stable disease with slow progression. Favourable survival and life-quality can be expected with this treatment also in patients with advanced midgut carcinoids.
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Affiliation(s)
- Göran Akerström
- Department of Surgery, University Hospital, Uppsala, Sweden.
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Marisavljevic D, Petrovic N, Milinic N, Cemerikic V, Krstic M, Markovic O, Bilanovic D. An unusual presentation of “silent” disseminated pancreatic neuroendocrine tumor. World J Gastroenterol 2004; 10:2919-21. [PMID: 15334702 PMCID: PMC4572134 DOI: 10.3748/wjg.v10.i19.2919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
To present a patient diagnosed with pancreatic carcinoid that was extremely rare and produced an atypical carcinoid syndrome. We reported a 58-year old male patient who presented with long standing, prominent cervical lymphadenopathy and occasional watery diarrhea. Pathohistological and immunohistochemical examination of lymph node biopsy showed a metastatic neuroendocrine tumor, which was histological type A of carcinoid (EMA+, cytokeratin+, CEA-, NSE+, chromogranin A+, synaptophysin+, insulin-). Bone marrow biopsy showed identical findings. Primary site of the tumor was pancreas and diagnosis was made according to cytological and immunocytochemical analysis of the tumor cells obtained with aspiration biopsy of pancreatic mass (12 mm in diameter) under endoscopic ultrasound guidance. However, serotonin levels in blood and urine samples were normal. It is difficulty to establish the precise diagnosis of a “functionally inactive” pancreatic carcinoid and aspiration biopsy of pancreatic tumor under endoscopic ultrasound guidance can be used as a new potent diagnostic tool.
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Abstract
Carcinoid tumors originate from the neuroendocrine cells throughout the body and are capable of producing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. We examined all aspects of carcinoid tumors including the molecular biology oncogenesis, role of angiogenesis, recent advances in imaging, and therapy. The Medline and Cancerlit databases were searched using carcinoid as the keyword. English language manuscripts were reviewed and relevant references from a total of 7741 were found. All titles were screened and all the relevant manuscripts were analyzed; we found 307 references pertinent to the history, epidemiology, clinical behavior, pathology, pathophysiology, molecular biology, radiologic imaging, supportive care of carcinoid syndrome, and results of therapeutic clinical trials. Management of patients with carcinoid tumors requires an understanding of the disease process and a multimodality approach. Introduction of long-acting somatostatin analogues has resulted in significant advances in the palliative care of patients with carcinoid syndrome. However, advanced carcinoid tumor remains incurable. Existing therapies for advanced disease have low biologic activity, high toxicity, or both. Clearly, more research is necessary in the areas of molecular biology, targeted therapy, and development of new drugs Future advances in this field need to focus on clinical and biological predictors of outcome. Early works in the area of tumor biology such as the role of p53, bcl-2, bax, MEN1, FGF TGF PDGF and VEGF expression are of interest and need to be explored further.
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Affiliation(s)
- Isac I Schnirer
- Department of Gastrointestinal Oncology and Digestive Diseases, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77005-4341, USA
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Abstract
A 30-year-old woman presented to the Emergency Department with complaints of shortness of breath, orthopnea, and a severe reduction in exercise tolerance. The symptoms were the result of severe valvular heart disease that resulted from a bronchopulmonary carcinoid tumor. The carcinoid syndrome is a distinctive clinical syndrome seen in patients with carcinoid tumors. Cardiac valvular lesions are seen in the majority of patients with the carcinoid syndrome and represent the most clinically significant consequence of the carcinoid syndrome. This case report discusses carcinoid tumors, the carcinoid syndrome induced by these tumors, and the therapeutic options in the management of carcinoid tumors.
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Affiliation(s)
- D Godshall
- Department of Emergency Medicine, Christiana Care Health System, Christiana Hospital, 4755 Ogletown-Staton Road, Newark, DE 19718, USA
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18
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Onaitis MW, Kirshbom PM, Hayward TZ, Quayle FJ, Feldman JM, Seigler HF, Tyler DS. Gastrointestinal carcinoids: characterization by site of origin and hormone production. Ann Surg 2000; 232:549-56. [PMID: 10998653 PMCID: PMC1421187 DOI: 10.1097/00000658-200010000-00010] [Citation(s) in RCA: 86] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To describe a large series of patients with carcinoid tumors in terms of presenting symptoms, hormonal data, stage at diagnosis, pathologic features, and survival. SUMMARY BACKGROUND DATA Published series have described significant prognostic features of carcinoid tumors as site of origin, age, sex, stage at diagnosis, presence of high hormone levels, and increased T stage. Of these, stage at diagnosis and T stage seem to emerge most often as independent predictors of survival in multivariate analyses. Of carcinoid tumors, those arising from a midgut location have higher levels of serotonin and serotonin breakdown products, as well as more frequent metastatic disease at presentation, than those arising from either foregut or hindgut locations. METHODS A prospective database of carcinoid patients seen at Duke University Medical Center was kept from 1970 to the present. Retrospective medical record review was performed on this database to record presenting symptoms, hormonal data, pathologic features, and survival. Statistical methods included analysis of variance, Kaplan-Meier analysis, and Mantel-Cox proportional hazard survival analysis, with P <.05 considered significant for all tests. RESULTS Carcinoids arising in different locations had different presentations: rectal carcinoids presented significantly more often with gastrointestinal bleeding, and midgut carcinoids presented significantly more often with flushing, diarrhea, and the carcinoid syndrome. Patients with midgut tumors had significantly higher levels of serotonin and serotonin breakdown products, corresponding to higher metastatic tumor burdens. Although age, stage, region of origin, and urinary level of 5-hydroxyindoleacetic acid predicted survival by univariate analysis, only the latter three were independent predictors of survival by multivariate analysis. Of the patients with metastatic disease at diagnosis, those with midgut tumors had better survival than those with foregut or hindgut tumors. CONCLUSIONS Although region of origin is certainly an important factor in determination of prognosis, stage of disease at presentation is more predictive of survival. Pancreatic and midgut carcinoids are metastatic at diagnosis more often than those arising in other locations, leading to a worse overall prognosis. Among patients with distant metastases, patients with midgut primary tumors have improved survival despite increased hormone production compared with patients with tumors arising in other primary sites.
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Affiliation(s)
- M W Onaitis
- Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
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19
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Shebani KO, Souba WW, Finkelstein DM, Stark PC, Elgadi KM, Tanabe KK, Ott MJ. Prognosis and survival in patients with gastrointestinal tract carcinoid tumors. Ann Surg 1999; 229:815-21; discussion 822-3. [PMID: 10363895 PMCID: PMC1420828 DOI: 10.1097/00000658-199906000-00008] [Citation(s) in RCA: 174] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To determine the impact of clinical presentation variables on the management and survival of patients with gastrointestinal (GI) tract carcinoid tumors. METHODS A 20-year (1975-1995) retrospective analysis of 150 patients with GI tract carcinoid tumors at the Massachusetts General Hospital was conducted. Median follow-up was 66 months (range 1-378). Survival estimates for prognostic factors were calculated using Kaplan-Meier product limit estimators, with death from carcinoid as the outcome. Univariate analyses for each factor were obtained using a log-rank test, and multivariate survival analysis was performed. RESULTS All but two patients underwent surgical intervention with the intent to cure (90%) or debulk the tumor (9%). Mean age at presentation was 55 +/- 18 years (range 11-90). There was a slight female/male predominance (80:70). Symptoms were nonspecific; the most common were abdominal pain (40%), nausea and vomiting (29%), weight loss (19%), and GI blood loss (15%). Incidental carcinoids, discovered at the time of another procedure, occurred in 40% of patients and were noted at multiple sites throughout the GI tract. The distribution of tumors was ileojejunum (37%), appendix (31 %), colon (13%), rectum (12%), stomach (4%), duodenum (1.3%), and Meckel's diverticulum (1.3%). Of the 27 patients with documented liver metastases, carcinoid syndrome developed in only 13 patients (48%), manifested by watery diarrhea (100%), upper body flushing (70%), asthma (38%), and tricuspid regurgitation (23%). All 13 patients with carcinoid syndrome had elevated levels of 5-HIAA, but the absolute levels did not correlate with the severity of symptoms. An additional 11 patients, 3 without liver metastases, had elevated levels of 5-HIAA without any evidence of carcinoid syndrome. Multicentric carcinoid tumors occurred in 15 patients (10%), and all but one of these tumors were centered around the ileocecal valve. There was no difference in the incidence of liver metastases between solitary (18%) and multicentric carcinoids (20%). Synchronous noncarcinoid tumors were present in 33 patients (22%), and metachronous tumors developed in an additional 14 patients (10%) in follow-up. Age and tumor size, depth, and location were significant predictors of metastases. By multivariate analysis, age > or = 50 years, metastases, and male gender were statistically significant predictors of death. CONCLUSIONS Gastrointestinal tract carcinoid tumors have a nonspecific clinical presentation, except in the case of the carcinoid syndrome. Surgical resection is the treatment of choice for improving survival. Surgically treated patients with carcinoid tumor have an overall favorable 83% 5-year survival rate.
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Affiliation(s)
- K O Shebani
- Department of Surgery, Massachusetts General Hospital, Boston 02114, USA
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20
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Sadler GP, Jones DL, Morgan JM, Neonakis E, Woodhead JS, Wheeler MH. Role of octreotide on release of intact 1-84 parathyroid hormone from human parathyroid cells. Br J Surg 1998; 85:1133-7. [PMID: 9718014 DOI: 10.1046/j.1365-2168.1998.00788.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Octreotide has been shown to lower urinary calcium in primary hyperparathyroidism although the mechanism remains unclear. This study examined the effect of octreotide on parathyroid hormone (PTH) secretion from human parathyroid cells in culture and as isolated cells. Additionally in situ hybridization was performed for somatostatin receptor messenger RNA (mRNA) and immunocytochemistry for somatostatin in eight parathyroid adenomas. METHODS Tissue from three hyperplastic glands and three adenomas was studied as dispersed cell suspensions. Incubation was in buffers containing high (2.0 mmol/l) and low (0.5 mmol/l) calcium concentrations, with or without octreotide 200 ng/ml. Cells were also seeded into tissue culture wells for 24 h to allow receptors to regenerate. Supernatant was removed at regular intervals and PTH levels were estimated using a two-site chemiluminescent assay. RESULTS Mean(s.e.m.) PTH secretion at 90 min in hyperplastic cells was 445(75) pmol/l in low calcium and 160(42) pmol/l in high calcium (P< 0.02), and in adenoma cells was 170(21) pmol/l in low calcium and 137(27) pmol/l in high calcium (P=0.37). There was no significant difference in secretion of PTH from cells incubated with octreotide either in culture or as dispersed cells. In situ hybridization failed to demonstrate any mRNA for the somatostatin receptors and no somatostatin was detected in any cells with immunocytochemistry. CONCLUSION Somatostatin has no direct action on PTH production and release from human parathyroid cells and is unlikely to be of any therapeutic value in the treatment of hyperparathyroidism.
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Affiliation(s)
- G P Sadler
- Department of Surgery, University Hospital of Wales, Heath Park, Cardiff, UK
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Abstract
BACKGROUND: Carcinoid tumors are the most frequently encountered endocrine tumors of the gastrointestinal tract. They are most often found in the appendix, although they can arise in any location of the gut. Carcinoid tumors may secrete a variety of bioactive substances, which can cause the complex of symptoms associated with the carcinoid syndrome. METHODS: The authors reviewed the pathology, clinical presentation, and management of carcinoid tumors with an emphasis on the surgical management. RESULTS: The primary treatment for a carcinoid tumor located anywhere in the gut is surgical. Those who have widely metastatic disease or who are anatomically unresectable may undergo cytoreductive surgical debulking and/or hepatic arterial embolization followed by palliation of symptoms with octreotide, the long-acting somatostatin analog. CONCLUSIONS: The prognosis for patients with carcinoid tumors that are fully resected is excellent. Those with hepatic metastases and the carcinoid syndrome have a less favorable prognosis.
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Affiliation(s)
- JF Sweeney
- Department of Surgery, University of Michigan, Ann Arbor 48105, USA
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Vasseur B, Cadiot G, Zins M, Fléjou JF, Belghiti J, Marmuse JP, Vilgrain V, Bernades P, Mignon M, Ruszniewski P. Peritoneal carcinomatosis in patients with digestive endocrine tumors. Cancer 1996. [DOI: 10.1002/(sici)1097-0142(19961015)78:8<1686::aid-cncr8>3.0.co;2-c] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Faiss S, Scherübl H, Riecken EO, Wiedenmann B. Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system. Recent Results Cancer Res 1996; 142:193-207. [PMID: 8893342 DOI: 10.1007/978-3-642-80035-1_12] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
Successful treatment of neuroendocrine tumor disease of the gastroenteropancreatic system requires a multimodal approach. Radical tumor surgery is required before other therapies are initiated. So far, only surgery has proven to be curative. If surgical intervention is not possible or a tumor-free state cannot be achieved, biotherapy with the somatostatin analogues octreotide or lanreotide should then be preferably carried out in patients with functional tumors. Interferon-alpha can alternatively be given. In patients with gastrinoma, therapy with proton pump inhibitors (e.g., omeprazol) is the initial treatment of choice. In patients with nonfunctional tumors, indication for treatment is only given in cases of documented tumor progress. In case of progressive tumor disease or functionality under the above-mentioned therapies, treatment with somatostatin analogues can be intensified by dose escalation or alternatively by a combination therapy with interferon-alpha and a somatostatin analogue. On the basis of the less favorable response of neuroendocrine foregut tumors to biotherapy, chemotherapy should be initiated after failure of biotherapy in documented tumor progression. A combination of streptozotocin and 5-fluorouracil, possibly combined with D,L-folinic acid, is the treatment of choice, considering the response and side effect rates. In case of predominantly anaplastic neuroendocrine tumors in advanced stages, good tumor response rates with a chemotherapeutic scheme consisting of cisplatin and etoposide can be achieved. Since the chemotherapy scheme is less effective in patients with midgut or hindgut tumors, chemoembolization of liver metastases should follow biotherapy. The response to chemoembolization may be increased by simultaneous systemic chemotherapy. Attention should always be paid to an adequate analgesic drug administration.
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Affiliation(s)
- S Faiss
- Department of Internal Medicine and Gastroenterology, Universitätsklinikum Benjamin Franklin, Free Universität Berlin, Germany
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Hauser H, Wolf G, Uranüs S, Klimpfinger M. Neuroendocrine tumours in various organ systems in a ten-year period. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 1995; 21:297-300. [PMID: 7781801 DOI: 10.1016/s0748-7983(95)91624-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Neuroendocrine cells are present in various organ systems. These widely distributed cells as well as their histogenetically related tumours can produce various peptides and peptide hormones. From 1984 to 1993, 349 neuroendocrine tumours were found among 511,382 histological diagnoses at the Institute of Pathology of the Medical School of the Karl Franzens University in Graz. In 30% carcinoid of the appendix was diagnosed, in 16% carcinoid of the colorectum, in 9% carcinoid of the small intestine and in 2% duodenal carcinoid. Carcinoid of the stomach was detected in 14%. Seven of these cases showed microcarcinoidosis and five of them were combined with an adenocarcinoma. Carcinoid of the oesophagus was present in 1%, neuroendocrine pancreatic tumours in 6%. Neuroendocrine tumours of the bronchial system were found in 12%, medullary thyroid cancer in 5%. In 1% a Merkel-cell tumour was diagnosed. Other more rare localizations of neuroendocrine tumours were the uterus, ovary, breast, testes, epididymis, anal region and the upper respiratory tract.
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Affiliation(s)
- H Hauser
- Department of Surgery, Medical School, Karl Franzens University, Graz, Austria
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25
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Ramage JK, Catnach SM, Williams R. Overview: the management of metastatic carcinoid tumors. LIVER TRANSPLANTATION AND SURGERY : OFFICIAL PUBLICATION OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES AND THE INTERNATIONAL LIVER TRANSPLANTATION SOCIETY 1995; 1:107-10. [PMID: 9346550 DOI: 10.1002/lt.500010207] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Chemotherapy, IFN, octreotide, and hepatic artery embolization can be useful for palliation, both of local symptoms and of the carcinoid syndrome, but they have little effect on tumor progression, MIBG therapy is still experimental but may have a future role. OLT should be considered as a palliative procedure in those patients with severe symptoms and no evidence of extrahepatic disease.
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Affiliation(s)
- J K Ramage
- Institute of Liver Studies, King's College Hospital, London, UK
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26
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Affiliation(s)
- S Cascinu
- Servizio di Oncologia, Ospedali Riunitii-Pesaro, Italy
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27
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Hussain A, Young ET, Greaves JD, Hammond PJ, Hughes JM, Wallis SC, Bloom SR. Intrapulmonary shunting causing hypoxaemia in a case of carcinoid syndrome. Clin Endocrinol (Oxf) 1994; 41:535-7. [PMID: 7955464 DOI: 10.1111/j.1365-2265.1994.tb02587.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
A case of metastatic carcinoid syndrome with hypoxaemia is described. The hypoxaemia appeared to be due to intrapulmonary shunting. There was improvement in resting and exercise arterial oxygen saturations following chemotherapy with streptozotocin and 5-fluorouracil. This was followed by a decrease in the tumour bulk which may have led to a reduction in the secretion of the vasodilator products responsible for shunting. Some features of this case suggest that the hypoxaemia might have been due to dilatation of precapillary and capillary vessels of the pulmonary micro-circulation. These features are part of the so-called 'hepatopulmonary syndrome', of which this case appears to represent a less severe form.
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Affiliation(s)
- A Hussain
- Department of Medicine, Wansbeck General Hospital, Northumberland, UK
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Oberg K. Expression of growth factors and their receptors in neuroendocrine gut and pancreatic tumors, and prognostic factors for survival. Ann N Y Acad Sci 1994; 733:46-55. [PMID: 7978895 DOI: 10.1111/j.1749-6632.1994.tb17255.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- K Oberg
- Department of Internal Medicine, University Hospital, Uppsala, Sweden
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Abstract
The follow up of a case of the carcinoid syndrome complicated by scleroderma is reported, in which progress of the disease may have been halted by treatment with a combination of cyproheptadine, parachlorophenylalanine and prednisolone. Impairment of tryptophan and 5-hydroxytryptamine (serotonin) metabolism appears central to the development of skin fibrosis in the carcinoid syndrome and may be indicative of important mechanisms in the pathogenesis of idiopathic scleroderma.
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Affiliation(s)
- R C Ratnavel
- Department of Dermatology, Addenbrooke's Hosital, Cambridge, UK
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Biesma B, Willemse PH, Mulder NH, Verschueren RC, Kema IP, de Bruijn HW, Postmus PE, Sleijfer DT, de Vries EG. Recombinant interferon alpha-2b in patients with metastatic apudomas: effect on tumours and tumour markers. Br J Cancer 1992; 66:850-5. [PMID: 1384643 PMCID: PMC1977979 DOI: 10.1038/bjc.1992.372] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Malignant carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid are tumours with similar clinical features. In patients with unresectable or metastatic tumours leukocyte interferon (IFN) and recombinant human (rh) IFN have demonstrated efficacy. Twenty-four evaluable patients with progressive tumours were treated with 2.5 megaunits rh IFN alpha-2b, administered once daily subcutaneously, for a median duration of 7 months (range 0.5-37+). Two carcinoid patients demonstrated a response in tumour size, 80% showed stable disease (SD). Sixty percent of the carcinoid patients with elevated urinary 5-hydroxyindoleacetic (5-HIAA) levels reached a biochemical partial response of the urinary 5-HIAA levels (median duration 13.5 months). In the patients with an islet cell or medullary tumour and an elevated tumour marker, the marker did not further increase. Of the 12 carcinoid patients evaluable for a symptomatic response, ten (83%) experienced a relieve of symptoms. IFN alpha-2b dose reduction or discontinuation due to toxicity was necessary in three and ten patients, respectively. No neutralising IFN alpha-2b antibodies developed despite prolonged treatment. In conclusion, IFN alpha-2b had a beneficial effect in patients with progressive tumours, while long-term IFN alpha-2b treatment did not augment neutralising antibodies. In view of the IFN alpha-2b-related toxicity, administration of IFN alpha-2b on alternating days may be preferable.
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Affiliation(s)
- B Biesma
- Department of Internal Medicine, University Hospital Groningen, The Netherlands
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32
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Veenhof CH, de Wit R, Taal BG, Dirix LY, Wagstaff J, Hensen A, Huldij AC, Bakker PJ. A dose-escalation study of recombinant interferon-alpha in patients with a metastatic carcinoid tumour. Eur J Cancer 1992; 28:75-8. [PMID: 1373635 DOI: 10.1016/0959-8049(92)90389-j] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The efficacy of interferon alpha-2b in doses up to 12 x 10(6) IU three times weekly was studied in 21 patients with a metastatic carcinoid tumour. Of these 21 patients, 19 were evaluable for response. Patients were treated with escalating dosages of interferon alpha-2b: 3 x 10(6) IU, 6 x 10(6) IU and 12 x 10(6) IU. The escalation was performed every 8 weeks when no objective tumour regression was observed. Patients were also evaluated for biochemical response and symptomatic improvement. One objective tumour regression was observed. Of the 15 patients with elevated 5-hydroxyindole acetic acid (5-HIAA) excretion, 5 (33%) had a more than 50% decrease in 5-HIAA excretion. Relief of symptoms occurred in 11 patients (58%). This improvement was already apparent during the initial 8 weeks of treatment. Increasing the dose to 6 or 12 x 10(6) IU interferon alpha-2b did not result in further symptomatic improvement. In contrast toxicity was considerable with the higher dosages of interferon alpha-2b. It is concluded that low dose interferon alpha-2b (3 x 10(6) IU) three times weekly is as effective as higher dosages of interferon alpha-2b at ameliorating symptoms of the carcinoid syndrome.
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Affiliation(s)
- C H Veenhof
- Division of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
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Ridolfi R, Amaducci L, Derni S, Fabbri L, Innocenti MP, Vignutelli P. Chemotherapy with 5-fluorouracil and streptozotocin in carcinoid tumors of gastrointestinal origin: experiences with 13 patients. J Chemother 1991; 3:328-31. [PMID: 1839743 DOI: 10.1080/1120009x.1991.11739114] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The Authors report their experiences on the treatment of 13 consecutive cases of gastro-intestinal carcinoid tumors observed over the last 11 years. The primary sites were as follows: intestine (5 cases), appendix (3 cases), colon (1 case) and peritoneum (4 cases); only 3 patients presented systemic signs. Ten patients in advanced phase were treated with a chemotherapeutic regimen containing 5-fluorouracil (5-Fu) and streptozotocin (STZ). One case was excluded from the study because of a concomitant gastric carcinoma. Of the 9 evaluable patients, two achieved partial remission (22%) with a duration of 18+ and 66 months respectively; 4 (44.5%) had stable disease for periods ranging from 7 to 40 months and 3 cases progressed. Severe toxicity (thrombocytopenia and diarrhea) occurred in 2 cases and disappeared with the suspension of therapy. The systemic signs disappeared with treatment and did not appear in 2 cases out of 3. The prospective of the employment of new drugs such as alpha-interferon and, above all, somatostatin provides hope that this uncommon disease may have an improved response rate to treatment in the future.
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Affiliation(s)
- R Ridolfi
- Unità Sanitaria Locale n. 38 Ospedali G.B. Morgagni-L. Pierantoni, Divisione di Oncologia, Forlì, Italy
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Affiliation(s)
- J M Feldman
- Durham VA Medical Center, Department of Medicine, North Carolina
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