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PubMed2003

The spectrum of carcinoid tumours and carcinoid syndromes.

Carcinoids are neuroendocrine tumours of the gut which may also be found in the bronchus, pancreatic islets and retroperitoneum. They probably arise from gastrointestinal or bronchopulmonary pluripotential stem cells. Carcinoid tumours derived from these cells are potentially malignant; the strength of the tendency for aggressive growth correlates with the site of origin, depth of local penetration and the size of the tumour. Carcinoids occur sporadically or result from specific hereditary tumour syndromes. Mutations and/or aberrant expression of specific genes induce and promote tumour growth. Clinical features include local symptoms due to angulation or obstruction and hepatomegaly due to liver metastases. The carcinoid syndrome commonly involves flushing, diarrhoea, bronchospasm and hypotension. Other distinct syndromes may be caused by tumour release of products that may also be used as biochemical markers in diagnosis and follow-up. Scanning using radiolabelled octreotide, an analogue of somatostatin, sensitively identifies occult primary and metastatic deposits. Localized carcinoid tumours should be resected. Some patients benefit from hepatic resection. Palliation of symptoms is best achieved with octreotide. Hepatic artery chemoembolization may produce long-acting palliation. Further genetic characterization of the different types and stages of carcinoid development as well as assessment of gene expression profiles may improve differential diagnosis, prognosis and treatment.

Carcinoid Tumor↗
PubMed1999

Bronchopulmonary carcinoids: An analysis of 1,875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties.

This study was undertaken to provide investigators working in this particular research field with extensive and useful basic information based on an analysis of a large reliable series of cases regarding tracheal and bronchopulmonary carcinoids and their atypical varieties. A statistical evaluation was carried out which included a total of 1,875 patients with tracheal and bronchopulmonary carcinoids; these were divided into two series, one of 1,595 patients with typical carcinoids and the other of 280 with atypical varieties. These two series were compared regarding various aspects, which included the male to female ratio, age distribution, clinical manifestations, successful preoperative diagnosis, diagnostic accuracy of representative procedures, sites of involvement, tumor size distribution, metastases, carcinoid syndrome, serotonin activity in patients with or without the syndrome, immunohistochemistry, electron microscopy, and postoperative prognosis of the patients. The comparative analyses between the two series disclosed statistically significant differences (p<0.01) regarding various viewpoints; among others, such a difference was proved in the average age, sites of involvement in the lung (central or peripheral), rates and sites of metastases, adrenocorticotrophic hormone (ACTH) production, the association rate of the carcinoid syndrome, and postoperative 5-year and 10-year survival rates (93.3% and 82.1% for the typical carcinoid series versus 68.8% and 58.6% for the atypical variety series: p<0.0001). The postoperative 5-year and 10-year survival rates in the other two groups of patients with or without metastases were likewise calculated and showed a statistically significant difference (72.8% and 52.8% for the former versus 98.3% and 95.4% for the latter: p<0.0001).

Adolescent↗
PubMed1995

[Successful treatment of carcinoid syndrome in two cases of bronchial carcinoid].

We encountered two patients with typical bronchial carcinoid and metastases to the liver who presented with typical carcinoid syndrome. In typical bronchial carcinoid without metastases to regional lymph nodes, recurrence and distant metastasis after curative resection are generally thought to be rare. The first patient was a 62-year-old woman who was admitted to our hospital because of facial flushing and diarrhea. She had undergone curative resection of a typical bronchial carcinoid 9 years earlier, and the postsurgical pathological stage was I. On the second admission, she was found to have multiple liver metastases. The second patient was a 59-year-old woman who was admitted to our hospital because of facial flushing, dyspnea, and dehydration due to diarrhea. She had undergone curative resection of a typical bronchial carcinoid 21 months earlier, and the postsurgical pathological stage was I. On the second admission, she was found to have multiple intrabronchial, bone, and liver metastases. Both patients were treated with subcutaneous injections of octreotide, and with transhepatic arterial chemoembolization. In addition, the second patient underwent percutaneous ethanol injection under ultrasonic guidance. Signs and symptoms disappeared soon after therapy began and the patients survived longer than expected. Hepatic artery chemoembolization and simultaneous chemotherapy can relieve symptoms in patients with carcinoid syndrome and multiple liver metastases, and self-administration of octreotide is the treatment of choice for immediate relief.

Antineoplastic Agents, Hormonal↗
PubMed1984

Oncocytic carcinoid of the nasal cavity and carcinoid of the lung in a child.

A 13-year-old girl with an oncocytic carcinoid of the nasal cavity and a bronchial carcinoid of classical type appearing one year later is reported. This investigation includes clinicopathological features, light and electron microscopic studies and immunohistochemical analysis of neuron-specific enolase (NSE) of both tumors as well as an enzyme histochemical analysis of the nasal tumor. Based on the light microscopic appearance and ultrastructural and enzyme histochemical findings, the nasal tumor was primarily diagnosed as an oncocytoma, but due to the finding of neurosecretory granules and positivity for NSE in tumor cells, we believe it should be regarded as an oncocytic carcinoid. To our knowledge, this is the first case reported in literature of a carcinoid in the nose of a child and also the first case of simultaneous carcinoids in the bronchi and nasal cavity. The relationship between the nasal and the bronchial tumors, their origin from foregut-derived respiratory mucosa and their probable multicentric origin as opposed to metastatic origin is discussed. Furthermore, the criteria stipulated for the diagnosis of a true oncocytoma and oncocytic carcinoids are briefly discussed.

Adenoma↗
PubMed1999

Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix.

Neuroendocrine tumors of the cervix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient's liver lesions and original cervical lesion ("adenocarcinoma") suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival.

Adenocarcinoma↗
PubMed1994

Gastric carcinoid: a rare form of gastrointestinal carcinoids. A report on three cases.

The stomach is an uncommon site for carcinoid tumors, the incidence of which is about 2% of all carcinoids. During a five-year period, from 1988 to 1992, three patients with gastric carcinoid tumors were diagnosed at the Tan Tock Seng Hospital, Singapore. Their ages ranged from 59 to 68 years, and all were male. Two patients were referred for investigation of anemia, and one patient presented with massive hematemesis and an advanced ulcerated tumor requiring emergency total gastrectomy. Of the other two patients, one had pernicious anemia with multiple carcinoid polyps, and the other had sessile carcinoid nodules. None of the patients had carcinoid syndrome. Two patients underwent gastrectomy, while the patient with polyps had an endoscopic polypectomy. Follow-up ranged from one to three years. Two patients remained well, but the patient who presented with an advanced tumor with serosal invasion and nodal involvement had hepatic recurrence and died two years after the diagnosis of recurrence.

Aged↗
PubMed1997

Regression of metastatic carcinoid tumor after valvular surgery for carcinoid heart disease.

BACKGROUND: The carcinoid syndrome is a common sequela in patients with carcinoid tumor metastatic to the liver. Cardiac involvement occurs in 19-56% of patients with symptomatic carcinoid syndrome and, in some patients, leads to valvular surgery to relieve symptoms due to progressive right-sided heart failure. Reports of these patients have emphasized amelioration of cardiac symptoms, but postoperative tumor status rarely has been discussed. METHODS: This report describes four patients who underwent valvular heart surgery for severe carcinoid heart disease and had regression of their metastatic carcinoid tumor postoperatively. RESULTS: All four patients had definite clinical improvement in cardiac function and relief of symptoms related to congestive heart failure postoperatively. Unexpectedly, they also had regression of their metastatic disease, as reflected in decreased levels of urinary 5-hydroxyindoleacetic acid, and objective evidence of a reduction in the size of hepatic metastases. CONCLUSIONS: To the authors' knowledge, these four patients represent the first reported cases of metastatic disease regression after valvular surgery for carcinoid heart disease. Further descriptions of tumor status in patients having undergone a heart operation for this disease would be valuable in determining the clinical significance of this finding.

Adult↗
PubMed1989

Primary ovarian carcinoid tumor in combination with carcinoid heart disease; a case report.

Primary ovarian carcinoid tumors (POCT) with secondary carcinoid heart disease are rare, only 13 cases have been reported in the literature to date. In most instances POCT can be completely removed surgically contrary to primary carcinoid tumor of the gastro-intestinal tract. Laparoscopy may be helpful in localizing the tumor. We present a case in which the carcinoid heart lesions progressed despite total eradication of the carcinoid.

Carcinoid Heart Disease↗
PubMed1984

Cardiovascular lesion of carcinoid syndrome. An autopsy case of bronchial carcinoid.

An autopsy case of a 67-year-old Japanese male is presented. He had been suffering from carcinoid syndrome for 5 years and showed a typical picture of carcinoid heart disease. In Japan, carcinoid heart disease is rare and we can find only four reported cases (33% of reported carcinoid syndrome). The patient had high urinary secretion of 5-HIAA and high serum serotonin, and finally he died of heart failure and bronchopneumonia. The primary site of this carcinoid tumor was of the bronchus of the right B10c , and it had large hepatic metastases. Electronmicroscopically, the tumor cells had secretory granules measuring 1500-3500 A in diameter. Immunohistochemically, the tumor cells were markedly positive for human chorionic gonadotropin (hCG) and antidiuretic hormone (ADH) and positive for serotonin, in both the primary site and hepatic metastases. Characteristic fibrous plaques were detected in the right atrium, tricuspid valve, right ventricle, and left atrium. Electron-microscopically, the fibrous plaques consisted of smooth muscle cells and myofibroblasts surrounded by basement membrane-like material. The abundant matrix of the fibrous plaques contained acid mucopolysaccharide, microfibrils and collagen fibers. The same fibrous plaques were also found in hepatic veins. Furthermore, retroperitoneal fibrosis was present, which showed proliferation of myofibroblasts, fibroblasts and immature mesenchymal cells.

Aged↗
PubMed2004

Complications of midgut carcinoid tumors and carcinoid syndrome.

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.

Carcinoid Heart Disease↗
PubMed1983

Effects of leukocyte interferon on clinical symptoms and hormone levels in patients with mid-gut carcinoid tumors and carcinoid syndrome.

We treated nine patients who had carcinoid tumors of the small intestine, six of whom had the carcinoid syndrome, with daily intramuscular doses of leukocyte interferon--3 X 10(6) U per day for one month and 6 X 10(6) U per day for another two months. Seven patients had previously been treated with streptozocin and fluorouracil, without benefit. Treatment with interferon ameliorated the manifestations of the carcinoid syndrome and led to prompt and continuing decreases in urinary levels of 5-hydroxyindoleacetic acid and serum levels of human chorionic gonadotropin subunits and pancreatic polypeptide in all six patients with liver metastases, but it had no clear effect in two of three patients with only lymph-node involvement. After the treatment period, five of the six responders had relapses in clinical manifestations and increases in hormone levels. We conclude that interferon is of benefit in treating metastatic small intestinal carcinoid tumors in patients with the carcinoid syndrome.

Aged↗
PubMedDate not supplied

[Management of digestive system carcinoid tumors and carcinoid syndrome].

INTRODUCTION: Carcinoid tumors are rare, most of the publications are case reports and the clinical series are uncommon. The quality of life and survival time of these patients depend on the adequate control of tumor growth and good palliation of their symptoms. AIMS: The purpose of this study is to inform epidemiological data and forms of management for these tumors and the Carcinoid Syndrome at the National Institute of Cancerology (INCan) at Mexico City in the last 15 years. METHODS: A retrospective review of the clinical records of patients diagnosed and treated at the INCan with carcinoid tumors from 1982 to 1997 was performed. RESULTS: The most common origin place was the gastrointestinal tract (GI), and the majority involved the right colon and the appendix. The longest survivors were patients with tumors originated in the appendix, tumors smaller than 2 cm or localized. At the time of diagnosis 47% of patients had metastatic disease that was also a poor prognostic factor. The experience in our hospital seem to support the use of interferon alone or in combination with octreotide or debulking surgery for the palliation of carcinoid syndrome. CONCLUSIONS: Carcinoid tumors are rare, and have a slow growth and less aggressive biological nature than noncarcinoid tumors. Treatment should be focused on trying to cure the small or localized lesions or to find the best palliative method for those symptomatic advanced lesions.

Adult↗
PubMed1986

Primary duodenal carcinoid with malignant carcinoid syndrome: a case report.

Primary duodenal carcinoid causing a malignant carcinoid syndrome is rare. Herein a case is reported. In view of this case and a review of the literature, the carcinoid syndrome is almost pathognomonic of massive liver metastasis or involvement of organs whose venous drainage is not through the portal system. The right upper quadrant abdominal pains accompanied by symptoms that resemble even part of the carcinoid syndrome should initiate the investigational process including proximal gastrointestinal endoscopy to avoid delay in diagnosis of duodenal carcinoid.

Carcinoid Tumor↗
PubMed1979

Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome.

One hundred eighteen patients with metastatic carcinoid tumor were randomized to treatment with streptozotocin combined with cyclophosphamide or with 5-fluorouracil (5-FU). Commonly experienced side effects were nausea, vomiting, leukopenia, thrombocytopenia, and nephrotoxicity. Objective response rates among eligible and evaluable patients treated with the 5-FU combination was 14 of 42 (33%) and with the cyclophosphamide combination, 12 of 47 (26%). Among those patients with carcinoids primary to the small bowel the respective response rates were 44% and 37%. The overall response rates for patients with carcinoids of pulmonary or unknown origin were only 12% and 17%. There was no significant difference in patient survival between the two treatment arms. Among 11 patients who received crossover therapy with 5-FU alone there were two responders. There were no responders among eight patients treated with cyclophosphamide alone. Urinary 5HIAA excretion proved to be a useful biologic marker in these patients that correlated well with the observed measurements of tumor bulk. Median survival times from the diagnosis of unresectable malignant disease related to sites of origin of carcinoid tumor were the following: small bowel, 28.4 months; pancreas, 24.0 months; lung, 15.1 months; and unknown origin, 9.0 months. Metastatic carcinoid tumor is a malignant disease susceptible to chemotherapeutic approaches and continued investigation of the therapy of these neoplasms should be strongly encouraged.

Adolescent↗
PubMed1999

Carcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid tumors.

BACKGROUND: Although ampullary carcinoid tumors (ACs) are often categorized clinically as duodenal carcinoid tumors (DCs), there are distinct clinical and pathologic differences. METHODS: Clinical, histopathologic, and immunohistochemical features of 12 ACs were compared with those of 53 DCs that did not involve the ampulla. RESULTS: Patients with AC were ages 28-74 years (mean, 54.9 years); 8 were males and 4 were females. Five were white and three were black; the race of four patients was not known. The size of ACs ranged from 0.2 to 5.0 cm in greatest dimension. There were no significant differences between AC patients and DC patients with respect to male predominance, race, tumor size, and mitotic rate. The insular growth pattern was more common in AC; the cribriform type was more common in DC. Four of 12 ACs contained psammoma bodies, versus none of 53 DCs (P = 0.001). The rate of metastasis was similar in patients with AC (4 of 12, 33%) compared with DC patients (14 of 53, 26%). In DC patients, involvement of the muscularis propria, a size greater than 2 cm, and mitotic activity were significantly correlated with metastatic risk. In AC patients, tumor size and mitotic activity had no correlation with metastatic potential. One AC had features of an atypical carcinoid tumor; there were none in the duodenal group. One-half of patients with AC presented with jaundice versus 7% of patients with DC (P = 0.005). Three patients (25%) with AC had von Recklinghausen disease versus 0 of 53 patients with DC (P = 0.003). Immunohistochemically, tumor cells expressed somatostatin in 67%, serotonin and cholecystokinin in 17%, insulin in 25%, and glucagon and gastrin in 0% of ACs. In contrast, 56% of DCs expressed gastrin (P < 0.001). CONCLUSIONS: Carcinoid tumors of the ampulla differ clinically, histologically, and immunohistochemically from carcinoid tumors elsewhere in the duodenum.

Adult↗
PubMed1992

Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth?

The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF-I-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-I. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-I-immunoreactive component eluting in the position of rhIGF-I, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.

Adult↗
PubMed1978

Multiple peripheral pulmonary carcinoids and tumorlets of carcinoid type, with restrictive and obstructive lung disease.

Multiple peripheral carcinoid tumors were found on lung biopsy in a 53 year old woman with an eight year history of pulmonary nodules. The biopsy specimen showed nodules varying from 1 to 7 mm in greatest diameter. The larger lesions were typical bronchial carcinoids whereas the smaller ones resembled pulmonary "tumorlets." Electron microscopy showed neurosecretory granules typical of carcinoids. The common multicentric origin of carcinoids and tumorlets from Kulchitsky cells is discussed. Pulmonary function testing revealed mild obstructive and restrictive defects, both attributed to the carcinoid tumors. The history, pathology and physiology of this unusual case are presented in detail, with a review of the literature. Obstructive airways disease, presumably due to the extensive bronchiolar involvement, has not previously been reported in this entity.

Airway Obstruction↗
PubMed1982

[The diffuse endocrine system and the carcinoids of the alimentary tract. Part I: Orthological aspects and common morphological features of the carcinoids (author's transl)].

Carcinoids arise from the so-called system of diffuse clear cells. Because of common histochemical properties it was proposed in the APUD-concept that these endocrine cells are of neural crest origin. As for the gastrointestinal tract endocrine cells this embryological derivation is disputed. Modern methods have led to the identification of about 18 distinct cell types. - According to the different localization of these cells in the alimentary canal the carcinoids show various histological structures i.e., a solid, trabecular, adenoid, undifferentiated and mixed growth. According to the reactivity to silver salts one can distinguish argentaffin, argyrophil and argyrophobe carcinoids. Biochemically and immunohistochemically some carcinoids are multihormonal, while others show paraendocrine hormone production. Small cell anaplastic carcinomas with endocrine granules are highly malignant variants of the carcinoids. There may be a mixed endo- and exocrine (amphicrine) differentiation in normal cells and in the so-called mucicarcinoids.

APUD Cells↗