Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome.
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PURPOSE: Subcutaneous (SC) octreotide acetate effectively relieves the diarrhea and flushing associated with carcinoid syndrome but requires long-term multiple injections daily. A microencapsulated long-acting formulation (LAR) of octreotide acetate has been developed for once-monthly intramuscular dosing. PATIENTS AND METHODS: A randomized trial compared double-blinded octreotide LAR at 10, 20, and 30 mg every 4 weeks with open-label SC octreotide every 8 hours for the treatment of carcinoid syndrome. Seventy-nine patients controlled with treatment of SC octreotide 0.3 to 0.9 mg/d whose symptoms returned during a washout period and who returned for at least the week 20 evaluation constituted the efficacy-assessable population. RESULTS: Complete or partial treatment success was comparable in each of the four arms of the study (SC, 58.3%; 10 mg, 66.7%; 20 mg, 71.4%; 30 mg, 61.9%; P> or =.72 for all pairwise comparisons). Control of stool frequency was similar in all treatment groups. Flushing episodes were best controlled in the 20-mg LAR and SC groups; the 10-mg LAR treatment was least effective in the control of flushing. Treatment was well tolerated by patients in all four groups. CONCLUSION: Once octreotide steady-state concentrations are achieved, octreotide LAR controls the symptoms of carcinoid syndrome at least as well as SC octreotide. A starting dose of 20 mg of octreotide LAR is recommended. Supplemental SC octreotide is needed for approximately 2 weeks after initiation of octreotide LAR treatment. Occasional rescue SC injections may be required for possibly 2 to 3 months until steady-state octreotide levels from the LAR formulation are achieved. (+info)
Prognosis and survival in patients with gastrointestinal tract carcinoid tumors.
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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. (+info)
Carcinoid constrictive pericarditis.
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A 78 year old man presented with diarrhoea, anorexia, and progressive lower limb oedema. He was in atrial fibrillation and had a right pleural effusion and ascites. Ultrasound of the abdomen and 24 hour urinary hydroxyindoleacetic acid output indicated metastatic carcinoid syndrome. Cardiac catheterisation revealed pericardial constriction, and pericardial exploration showed a greatly thickened pericardium with no evidence of tumour invasion. The patient died within 24 hours of surgery. Necropsy findings were consistent with a diagnosis of constrictive pericarditis secondary to metastatic carcinoid syndrome. (+info)
Gastrointestinal carcinoids: characterization by site of origin and hormone production.
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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. (+info)
Occurrence and effects of octreotide antibodies during nasal, subcutaneous and slow release intramuscular treatment.
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OBJECTIVE: Previous studies have indicated that antibody formation against octreotide is extremely rare. We examined the occurrence of octreotide antibody formation after treatment with three administration forms in large populations of patients with acromegaly or carcinoid syndrome. DESIGN: (i) Nasally administered octreotide: 70 previously untreated patients and 81 previously s.c. octreotide-treated patients participated. (ii) Subcutaneously administered octreotide: 172 acromegalic patients and 59 patients with carcinoid syndrome treated for up to 12 years participated. (iii) Intramuscularly administered depot octreotide (Sandostatin LAR): 62 acromegalic patients participated. METHODS: Presence of antibodies is defined as increased precipitation by polyethylene glycol of (125)I-octreotide after incubation with serum; this was also used for screening of cross-reaction with somatostatin and lanreotide (Somatuline). RESULTS: In patients who received nasal octreotide for at least 9 and up to 12 months (n=42), the occurrence of octreotide antibodies was 77% and 81% for previously untreated and treated patients respectively. In subcutaneously treated patients it was 63/231 (27%) after a mean exposure of 3 years. In patients treated for more than 5 years (n=53) it was 57% and after 8 years (n=18) 72%. In contrast, no patient could with certainty be identified to be antibody-positive after a mean of 2.5 years intramuscular Sandostatin LAR treatment (n=47). In all populations, the antibody-positive patients were as well controlled as the antibody-negative patients. Octreotide antibodies did not cross-react with native somatostatin (n=141), while about 25% of the antibody-positive sera did cross-react with the somatostatin analogue, lanreotide (Somatuline, Ipstyl, Angiopeptin). CONCLUSIONS: Antibody formation against octreotide is much more frequent than previously believed. It depends primarily on drug exposure time and route of administration. It does not alter the GH/IGF-I status in treated acromegalic patients and induces only mild local reactions in some patients. (+info)
Hepatic artery ligation in treatment of carcinoid syndrome.
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SUMMARY: In a patient with malignant carcinoid syndrome with metastasis to the liver, cardiac lesions, pulmonary hypertension, pellagra-like skin lesions and depression developed. Her disability progressed despite medical therapy and two courses of chemotherapy. The primary tumour had been resected but the metastatic mass in the liver could not be resected because of its anatomic position. The dramatic improvement after hepatic artery ligation was correlated with urinary 5-hydroxyindole acetic acid excretion. (+info)
Perianaesthetic risks and outcomes of abdominal surgery for metastatic carcinoid tumours.
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Patients with metastatic carcinoid tumours often undergo surgical procedures to reduce the tumour burden and associated debilitating symptoms. These procedures and anaesthesia can precipitate a life-threatening carcinoid crisis. To assess perioperative outcomes, we studied retrospectively the medical records of adult patients from 1983 to 1996 who underwent abdominal surgery for metastatic carcinoid tumours. Preoperative risk factors, intraoperative complications and complications occurring in the 30 days after surgery were recorded. Perioperative complications or death occurred in 15 of 119 patients (12.6%, exact confidence interval 7.2-19.9). None of the 45 patients who received octreotide intraoperatively experienced intraoperative complications compared with eight of the 73 patients (11.0%) who did not receive octreotide (P=0.023). The presence of carcinoid heart disease and high urinary output of 5-hydroxyindoleacetic acid preoperatively were statistically significant risk factors for perioperative complications. (+info)
A woman aged 46 was found to have severe tricuspid valve disease 14 years after the diagnosis of a malignant carcinoid tumour of the ileum and 33 years after the onset of symptoms attributable to the disease. Increasing ascites requiring repeated paracentesis had not responded to chemotherapy including infusion of 5-fluorouracil and vincristine into the coeliac artery. The tricuspid valve was replaced by a Bjork-Shiley prosthesis. After operation there was no recurrence of ascites or oedema. She remains well one year and 11 months later. It is suggested that valve replacement surgery should be considered more often in patients with carcinoid heart disease. Hepatomegaly and ascites sould not be attributed too readily to advancing malignant disease without careful consideration of the role of right-sided valvar lesions in the production of these signs. (+info)