Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate.

Survival in patients with metastatic carcinoid tumors is dependent on control of tumor growth and adequate palliation of vasoactive amine-induced symptoms of flushing, diarrhea, wheezing, and valvular heart disease. Eight patients with carcinoid tumors metastatic to the liver were treated with long-term octreotide acetate therapy (100 to 500 micrograms three times a day), intra-arterial 5-fluorouracil infusion (2 g/day x 5 days), and hepatic tumor chemoembolization. All eight patients became asymptomatic and have remained so with a mean follow-up duration of 22 months from the time of first infusion. Following institution of subcutaneous octreotide acetate, intra-arterial infusion, and tumor chemoembolization, all patients are alive with a mean survival of 40 months from the time of diagnosis of carcinoid syndrome (range: 2 to 108 months). Four patients had greater than a 50% decrease in tumor size after therapy (mean follow-up duration: 10.6 months), and the other four patients have had stable disease after institution of therapy. It appears that combinations of long-term subcutaneous administration of octreotide acetate, intra-arterial 5-fluorouracil, and tumor chemoembolization effectively control progressive liver metastasis and provide excellent symptomatic palliation in patients with hepatic metastasis from functional carcinoid tumors.     

Primary carcinoid tumor of the bilateral testis associated with carcinoid syndrome

Carcinoid tumors derived from neuroendocrine cells can release serotonin and other vasoactive substances into the systemic circulation, resulting in carcinoid syndrome. Testicular carcinoid, a rare disease accounting for less than 1% of all testicular neoplasms, rarely manifests symptoms of carcinoid syndrome. We describe a case of carcinoid syndrome arising from a primary testicular carcinoid tumor. A 21-year-old male patient presented with facial flushing and diarrhea for 5 years. He had an enlarged left testis and a 1-cm, ill-defined, hard, non-tender mass in his right testis. His 24 h urinary excretion of 5-hydroxyindoleacetic acid was elevated (16.1 mg/day). Somatostatin receptor scintigraphy correlated with carcinoid tumor in both testes. Following bilateral orchiectomy, the patient's facial flushing and diarrhea disappeared.     

Primary carcinoid of the testis associated with carcinoid syndrome

Testicular carcinoid is a rare disease accounting for less than 1% of all testicular neoplasms. It rarely manifests symptoms of carcinoid syndrome. Recent reports have noted that only 1.1-3.1% of testicular carcinoid tumors are complicated by carcinoid syndrome. In general, large tumor size and the presence of carcinoid syndrome are features associated with a malignant course. In the present case, pathological findings revealed pure carcinoid of the testis without metastasis. Moreover, watery diarrhea due to carcinoid syndrome disappeared and the serum serotonin level normalized following orchiectomy. The patient was followed up for 12 months with whole body computed tomography scan and assessment of serotonin levels. To date, there is no evidence of tumor recurrence. These findings suggest that monitoring serum serotonin levels may be useful as a marker during follow up of this type of tumor.     

Facial flushing due to recurrent bronchial carcinoid

Carcinoid syndrome is quite a rare presentation in bronchial carcinoid. A review of the literature suggests a figure of 2% to 7% in various series. This is usually associated with recurrent carcinoid tumor in the presence of hepatic metastasis. We discuss a patient who presented with flushing attacks 13 years after a left pneumonectomy. Further investigation found that the patient had recurrence at the pneumonectomy stump and in subcarinal lymph nodes.     

Primary hepatic carcinoid tumor in children

Primary carcinoid tumors of the liver are rare, with fewer than 60 cases currently reported in the English literature. We present the evaluation and management of a solid hepatic tumor in a 14-year-old boy. Intraoperative biopsy was indeterminant for malignant potential, and the patient underwent complete resection by left hepatic lobectomy. Final histopathologic evaluation of the mass revealed a carcinoid tumor.Extensive endoscopic and radiologic workup revealed no other primary source. The patient recovered well from surgery and is currently free of disease 32 months after initial resection. Review of the literature suggests that primary hepatic carcinoid tumors are particularly rare in children. As the liver is frequently a site for carcinoid metastasis from the gastrointestinal tract, any patient with a suspected primary hepatic carcinoid tumor must undergo an extensive search for an extrahepatic primary site. These tumors are typically indolent but may metastasize. In addition, medical therapy is of limited benefit in reducing tumor bulk. The mainstay for treatment of primary hepatic carcinoid tumors is surgical resection, and these tumors carry a more favorable prognosis than other primary hepatic malignancies and metastatic carcinoid. Follow-up is long-term, as these tumors can recur many years after initial resection.     

Hepatic dearterialization in the treatment of carcinoid syndrome

Fourteen patients with carcinoid syndrome due to metastatic ileal (10), ileo-coecal (3) or appendiceal (1) carcinoid tumours were treated with hepatic dearterialization procedures: 15 surgical interruptions of arterial connections to the liver and 1 angiographic embolization of hepatic arteries. 11 patients had complained of recurrent attacks of flush, diarrhea and/or dyspnea and 3 patients had already progressed to general debility and cardiac failure caused by tumour products. Hepatic dearterialization abolished the carcinoid syndrome symptoms for 3-60 months (mean 19 months). Urinary 5-HIAA decreased for a mean period of 27 months. After relapsing symptoms 2 patients had redearterialization of the liver with a renewed symptomless period and lowered 5-HIAA excretion. Operative mortality was 19%: the deaths occurred when liver dearterialization was performed for end-stage patients or simultaneously with bowel resection, which should be considered as contraindications. Hepatic dearterialization seems to be temporarily effective in relieving carcinoid syndrome symptoms and in reducing hormonally active tumour mass and serotonin formation.     

Our experience regarding biologically inactive gastroenteropancreatic neuroendocrine tumors

The Authors present 9 cases of gastro-enteropancreatic neuro-endocrine biologically inactive tumors. In 5 cases the tumor site was appendicular. In 4 patients an appendectomy was performed, in one patient a right hemicolectomy and the patients after a period of 3-9 years are well and disease free. In a patient with a gastric carcinoid and a single hepatic metastasis a total gastrectomy with an hepatic metastasectomy were performed but the patient died 16 months thereafter. In a case localized to the right colon with a single hepatic metastasis a right hemicolectomy was performed with a metastasectomy but the patient died after 12 months. In a case localized to an ileal loop a segmental resection was performed followed by a medical therapy with octreotide and the patient is well and disease free after 3 years. In a case localized to the pancreas with widespread lymphatic metastasis it was performed a simple biliary diversion (coledocho-duodenostomy) followed by medical therapy with octreotide. Surprisingly after 4 years the patient is alive and a TC control shows a decrease of the pancreatic tumor and of the lympho glandular tumefactions.     

Carcinoid of the digestive tract. An analysis of 36 cases]

36 cases of carcinoid of the digestive tract were presented. The malignancy of the carcinoid was established solely by the presence of local infiltration and remote metastasis irrespective of the size of the original tumor three of 10 cases of the tumor less than 2 cm in diameter had metastasis although smaller tumors were usually benign. Immuno-histochemistry study in 15 cases showed 1-4 kinds of different polypeptides in each case. Three of 8 cases of malignant carcinoid syndrome had normal blood level of 5-HT and 5-HIAA, suggesting other polypeptides as the cause of the syndrome. The absence of hepatic metastasis in 4 of the 8 cases favors the hypothesis that polypeptides may get access to the general circulation by such as retroperitoneal pathways.     

Malignant carcinoid of the last ileal ansa. Report on 2 consecutive clinical cases

Carcinoid tumors are very rare neoplasms, arising from enterochromaffin cells, classified in Apud system, exhibiting an intermediate malignancy, because of their long lasting clinical silence and low evolution to advanced stage. At the same time, these features unfortunately cause a high incidence of lymphatic and liver metastases, visible at first diagnostic approach, which are also determined by aspecific symptoms and signs, especially involving jejunal and ileal carcinoids, as the two cases described, and by very frequent absence, in current clinical practice, of pathognomonic carcinoid syndrome. Two carcinoids located into the distal ileal ansa, strictly adjacent to the ileocecal valve, are reported; the first tumor, accompanied by lymphonodal positivity, the second by a solitary hepatic metastasis, requiring segmentectomy of the liver, in addition to right hemicolectomy.     

Gastrointestinal carcinoid tumors

Fifty-five patients were evaluated and treated for gastrointestinal (GI) carcinoid tumors at our institution from 1968 through 1988. Thirty patients had primary tumors smaller than 1 cm and were treated surgically or endoscopically by local excision, whereas 25 underwent resection with regional lymphadenectomy for larger primaries. At the time of initial treatment 17 patients demonstrated metastasis. Although 13 of these patients had primary tumors larger than 2 cm, in four patients with ileal carcinoids, the primary measured 0.8 to 1.5 cm. Serosal involvement was present in nine of 17 patients with metastasis. With a follow-up range of 3 months to 20 years, six patients have died with metastatic carcinoid tumor, two patients died without evidence of disease, 12 patients are alive with metastasis, and 35 patients are alive, free of disease. In this series three determinants for risk of metastasis in GI carcinoid tumors were evident: primary size, serosal penetration, and primary site in the small intestine. In patients with any of these risk factors, resection with regional lymphadenectomy is recommended.     

The pentagastrin test in the diagnosis of the carcinoid syndrome. Blockade of gastrointestinal symptoms by ketanserin.

The levels of 5-hydroxytryptamine (serotonin, 5-HT) and substance P (SP) were assayed (using high performance liquid chromatography-electron capture and radioimmunoassay methods) in the peripheral blood of 17 patients with known mid-gut carcinoids, 16 of whom had hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal changes induced by two provocation tests, intravenous pentagastrin (PG) and calcium infusion, were compared. Pentagastrin caused flushing in all the patients, induced gastrointestinal symptoms in all but one of the patients with hepatic involvement, and universally elevated circulating 5-HT levels. Pretreatment with a 5-HT2-receptor blocking agent, ketanserin, abolished the gastrointestinal effects but had virtually no influence on either 5-HT levels or flushing induced by intravenous pentagastrin. In contrast, calcium infusion induced carcinoid symptoms in only two of six patients, and this was consistently associated with stimulation of circulating serotonin levels. The authors conclude that 1) 5-HT may be responsible for the gastrointestinal symptoms in carcinoid patients, but it does not seem to play any role in flushing; 2) ketanserin may be a useful therapeutic agent in alleviating gastrointestinal symptoms in carcinoid patients; 3) differential responses to PG suggests that SP is released from a site different from that of 5-HT; 4) it is possible that SP may contribute to the mediation of flushing, but it cannot be the sole agent causing this symptom; and 5) the pentagastrin test with measurements of 5-HT levels in peripheral blood seems to be superior to calcium infusion as a provocative test in documenting the diagnosis of carcinoid disease.     

Right lobe living related graft loss due to intrahepatic multiple arterio-portal fistulas

We report a case of a 38-year-old Caucasian female with ileal carcinoid and bilobar hepatic metastases. After resection of the primary tumor, octreotide therapy was prescribed. Carcinoid histology was positive for chromogranin A and sinaptophsine and negative for MIB1. At 1-year, a follow-up computed tomography scan, Octreoscan, and PET scan were negative for extrahepatic involvement. The patient underwent right lobe living related liver transplantation donated by her sister. Acute hepatic artery thrombosis was successfully revascularized 24 hours after transplantation. Extrahepatic biliary ischemia was treated by a bilio-digestive anastomosis. Eight months later, ascites and clinical and serologic signs of liver failure developed; a liver biopsy revealed fibrosis. Spiral computed tomography scan and hepatic angiography showed multiple intrahepatic arterio-portal fistulas resulting in arterialization and inversion of the portal flow in the absence of graft outflow obstruction.     

Treatment of the carcinoid syndrome by hemihepatectomy and radical excision of the primary lesion

Two patients with the carcinoid syndrome whose symptoms were difficult to control with drugs and who had early signs of right heart valvular changes are reported on. Left hemihepatectomy was believed to be justified; resection of the left half of the liver, a tumor of the small bowel, and lymph node secondaries in one patient and resection of a tumor of the small bowel and the quadrate hepatic lobe in another patient resulted in symptom-free periods of twelve and four months, respectively. These cases support the adoption of more aggressive surgical treatment of this manifestation of carcinoid tumors.     

Primary carcinoid tumor in an ileal conduit

Carcinoid tumors are neuroendocrine tumors that typically arise in the gastrointestinal tract. We present the case of a 74-year-old woman with a primary carcinoid tumor in an ileal conduit urinary diversion who presented with gross hematuria. We also provide a brief review of relevant reports. The patient subsequently underwent resection and replacement of her ileal conduit.     

Resection of carcinoid tumors of the small intestine is still indicated in the presence of disseminated hepatic metastases]

The authors report their experience with resection of small bowel carcinoid tumors associated with diffuse hepatic metastases. Nine patients were operated during the last ten years. A carcinoid syndrome was present biologically in every case and clinically in 8 cases. The tumor was removed in every case, either by right hemicolectomy (n = 6), or by small bowel resection (n = 3). Postoperative mortality and morbidity were nil. Adjuvant therapy included hepatic chemo-embolization and long-term therapy by a long-acting somatostatin analog. Five patients died during the period of follow-up and 4 patients were alive at the end of the study. Resection of small bowel carcinoid tumor is indicated even when the liver is involved by diffuse metastases to prevent the risk of small bowel occlusion, and to promote hepatic chemoembolization as subsequent therapy against the carcinoid syndrome and metastatic spread. Moreover, the procedure can participate in the selection of cases for orthotopic liver transplantation, when conservative therapy fails to control the carcinoid syndrome.     

Hepatic resection and transplantation for primary carcinoid tumors of the liver

OBJECTIVE: To discuss the diagnosis and management of primary carcinoid tumors of the liver in light of our experience and a literature review. SUMMARY BACKGROUND DATA: Carcinoid tumors of the liver are rare and pose a diagnostic and management dilemma. This series is the largest reported and the only one to include liver transplantation as a treatment option. METHODS: Between March 1994 and May 2002, we treated 8 patients (4 male, 4 female) with primary hepatic carcinoid tumors. Carcinoid syndrome complicated only 1 of the cases. Treatment was by liver resection in 6 patients and orthotopic liver transplantation in 2. RESULTS: The diagnosis was confirmed histologically with light microscopy and immunohistochemistry in the absence of an alternative primary site. Six patients remain alive and disease free after follow-up of more than 3 years: 39, 43, 45, 50, 50, and 95 months. Two patients are recently postoperative. CONCLUSIONS: Active exclusion of an extrahepatic primary site is essential for the diagnosis of primary carcinoid of the liver. The mainstay of treatment should be liver resection, although liver transplantation may be considered in patients with widespread hepatic involvement. A radical surgical approach is warranted as this disease carries a better prognosis than for other primary hepatic tumors and for secondary hepatic carcinoids.     

Aggressive surgery for metastatic liver neuroendocrine tumors

BACKGROUND: Neuroendocrine tumors of the gastrointestinal tract (carcinoids, pancreatic endocrine tumors) have low malignant potential but can decrease survival rates if they spread to the liver (LNET). METHODS: The records of 16 patients with LNET primarily from gastrointestinal carcinoids treated surgically were retrospectively reviewed. RESULTS: There were 12 women and 4 men. Median age was 56 years (range 25 to 75). Thirteen (81%) had a carcinoid tumor and 5 had gastrinoma. Two patients with multiple endocrine neoplasia type 1 had both a gastric carcinoid and a jejunal gastrinoma. Eight patients (50%) had the carcinoid syndrome. Each patient had all identifiable LNET either resected or ablated. Ten patients had liver wedge resections, 1 right trisegmentectomy, 5 left hepatic lobectomies, and 2 radiofrequency ablations. Thirteen (81%) patients had concomitant bowel resections. Two patients had concomitant total gastrectomies to remove stomach primaries. The final patient had an extraintestinal pelvic primary or a liver primary. There were no operative deaths, and all 8 (100%) patients with the carcinoid syndrome had amelioration of symptoms. The 5-year actuarial survival rate was 82% with a median follow-up of 32 months. CONCLUSIONS: This study demonstrates that liver and concomitant extrahepatic surgery can be performed safely in patients with liver metastases because of carcinoids or pancreatic endocrine tumors. It results in excellent long-term survival and amelioration of symptoms. Surgery should be the first-line therapy for patients with LNET.     

Anaesthetic management of a patient with carcinoid tumor undergoing myocardial revascularization

Carcinoid tumors with hepatic involvement can produce intense flushing, tachycardia, hypotension or hypertension and diarrhoea. Patients with limited cardiac reserve may not tolerate these effects under anaesthesia. Valvular heart disease associated with carcinoid tumors has been reported, but there is no record in the literature of such an association with coronary artery disease. This report presents the anaesthetic management of a patient with coronary artery disease and carcinoid tumor undergoing myocardial revascularization. Emphasis is placed on the rational use of anaesthetic and adjunctive agents which will minimize the incidence of carcinoid symptoms. The salient features of the management are prevention of release of vasoactive substances by the use of promethazine hydrochloride during operation, the avoidance of atropine, prophylactic administration of corticosteroids and smooth induction of anaesthesia by the use of diazepam and dimethyl-tubocurarine iodide (Metocurine).     

Perianesthetic management of carcinoid syndrome: contribution of the bispectral EEG index

This case report described the perioperative management of a patient undergoing laparotomy for ileal carcinoid tumor with liver metastases and preoperative carcinoid syndrome. During surgery, bispectral index monitoring, combined with classical blood pressure and heart rate, allowed to discriminate hypertension related to the carcinoid syndrome, from hypertension reflecting an inadequate level of anaesthesia. Consequently, adequate treatment by a somastotatin analogue could be early administered.     

Antrectomy for multicentric, argyrophil gastric carcinoids: a preliminary report

Multicentric gastric carcinoids develop infrequently in association with atrophic gastritis, achlorhydria, and hypergastrinemia. These unusual tumors, thought to arise from proliferation of enterochromaffin-like (ECL) cells, have not been shown to secrete any measurable biogenic amines and usually grow slowly. Hypergastrinemia, which results from antral G cell stimulation secondary to atrophic gastritis, is believed to be the trophic stimulus, but alternative explanations include production of gastrin-releasing factor (GRF) or gastrin per se by the tumor. We recently encountered two patients with pentagastrin-resistant achlorhydria and multiple gastric carcinoids. Neither had symptoms of carcinoid syndrome. Urinary 5-hydroxyindoleacetic acid and serum human pancreatic polypeptide, vasoactive intestinal peptide, and motilin values were normal. Fasting gastrin values were nearly 1800 pg/ml. Antrectomy and regional lymphadenectomy was performed in each patient. The tumors were locally invasive with penetration through the submucosa. One patient had regional lymph node involvement, and one had an isolated hepatic metastasis. Immunohistochemical stain tests were positive in both patients for neuron-specific enolase and chromogranin, with focal positive staining for gastrin and serotonin. Serum gastrin levels decreased to less than 25 pg/ml after antrectomy. Evaluation with upper gastrointestinal endoscopy and biopsy examination 4 to 6 months after antrectomy showed complete regression of disease in one patient and residual neoplasm in one patient, despite normal serum gastrin levels. Additional studies with careful long-term follow-up will be needed to determine whether antrectomy eliminates the hypergastrinemia associated with enterochromaffin-like hyperplasia and leads to regression of disease.