piperidines and Carcinoid-Tumor

Ibrutinib is an orally administered inhibitor of Bruton's tyrosine kinase (Btk). Preclinical data suggest that mast cells are recruited within neuroendocrine neoplasms (NENs) where they stimulate angiogenesis and tumor growth. Ibrutinib inhibits mast cell degranulation and has been associated with regression of tumors in a mouse insulinoma model.. A prospective, phase II trial evaluated patients with advanced gastrointestinal (GI)/lung NENs and pancreatic NENs (pNENs) who had evidence of progression within 12 months of study entry on at least one prior therapy. Patients received ibrutinib 560 mg daily until unacceptable toxicity, progression of disease, or withdrawal of consent. The primary endpoint was objective response rate.. Twenty patients were enrolled on protocol from November 2015 to December 2017 (15 advanced GI/lung NENs and 5 pNENs). No patient reached an objective response. Median PFS was 3.0 months. A total of 44 drug-related adverse events (AEs) were captured as probably or definitely associated with ibrutinib. Five patients experienced probably or definitely related grade 3 AEs, and 1 patient experienced a probably related grade 4 AE. Five patients discontinued treatment prior to radiographic assessment.. Ibrutinib does not show significant evidence of activity in well-differentiated gastroenteropancreatic and lung NENs.

Topics: Adenine; Adult; Agammaglobulinaemia Tyrosine Kinase; Aged; Carcinoid Tumor; Female; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Piperidines; Prospective Studies; Protein Kinase Inhibitors; Treatment Failure

Both severe hypokalemia and persistent hypertension are clinical symptoms of hyperaldosteronism. Hyperaldosteronism may occur as a primary or secondary syndrome. Excess ACTH produced ectopically by tumors may induce hyperaldosteronism through the mineralocorticoid activity of glucocorticoids that are upregulated by ACTH. Licorice, with the active ingredient glycyrrhiza, is also a well-known inducer of hyperaldosteronism under specific conditions. In this report, we describe a case of severe hypokalemia caused by ectopic ACTH syndrome (EAS) elicited by an intrathoracic carcinoid tumor, which had transformed to produce ACTH during the 6-year clinical course, and was modulated by licorice ingestion. Hypokalemia was not clearly recognized preoperatively but became obvious within 3 h of general anesthesia with epidural blockade. At the end of anesthesia, arterial blood gas analysis indicated severe hypokalemia ([K(+)] = 1.7 mEq/l) and metabolic alkalosis (pH 7.56, PaCO(2) = 54.9 mmHg, HCO(3)(-) = 44.5 mmol/l, BE = 21.8 mmol/l), without any typical symptoms such as muscle weakness or ECG abnormalities. The hypokalemia was resistant to potassium supplementation and persisted for 4 days. Perioperative imbalance between the administration and elimination of potassium and surgical stress might contribute to the rapid exacerbation and induce the clinical manifestation of EAS.

Topics: ACTH Syndrome, Ectopic; Adjuvants, Anesthesia; Anesthesia; Anesthetics, Intravenous; Blood Gas Analysis; Blood Pressure; Carcinoid Tumor; Fentanyl; Heart Rate; Hormones; Humans; Hypertension; Hypokalemia; Male; Middle Aged; Nicardipine; Perioperative Period; Piperidines; Pneumonia, Pneumocystis; Psychotic Disorders; Remifentanil; Thoracic Neoplasms; Tomography, X-Ray Computed

Topics: Blood Pressure; Carcinoid Tumor; Cardiopulmonary Bypass; Female; Histamine Release; Humans; Intraoperative Care; Intraoperative Complications; Ketanserin; Middle Aged; Piperidines; Preoperative Care; Serotonin; Tricuspid Valve; Tricuspid Valve Insufficiency

Serotonin (5-HT) and substance P (SP) were assayed in peripheral blood in patients with known midgut carcinoids and hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal response was evaluated by two provocation tests, pentagastrin (PG) injection or calcium infusion. Pentagastrin caused flushing and gastrointestinal symptoms and elevated levels of circulating 5-HT, but not of SP. Pretreatment with a 5-HT2 receptor blocking agent (ketanserin) alleviated gastrointestinal symptoms but had no influence on either 5-HT release or PG-induced flushing. Calcium infusion induced carcinoid symptoms in only two of six patients, which were associated with elevated 5-HT levels (whereas elevated SP levels were seen in only one patient). We conclude that 5-HT is important for the development of gastrointestinal symptoms but not of flushing. Ketanserin may alleviate gastrointestinal symptoms but does not influence PG-induced release of 5-HT. Substance P and 5-HT do not seem to share a common release mechanism. It appears that PG testing is superior to calcium infusion as a provocative test in patients with the carcinoid syndrome.

Topics: Carcinoid Tumor; Female; Gastrointestinal Neoplasms; Humans; Hydroxyindoleacetic Acid; Ketanserin; Male; Malignant Carcinoid Syndrome; Pentagastrin; Piperidines; Receptors, Serotonin; Serotonin Antagonists; Substance P; Time Factors

19 consecutive patients admitted with severe chronic diarrhoea which had failed to respond to standard therapeutic regimen were treated with 4 to 8 mg of loperamide daily for up to 50 weeks. A marked improvement was achieved in 13 out of the 19 patients (68%). The best results were observed in patients with ulcerative colitis and Crohn's disease. Patients with secretory diarrhoea did not improve. No major side effects were observed. It is concluded that loperamide is a highly effective and safe new drug in the treatment of patients with chronic inflammatory bowel diseases.

Topics: Adult; Aged; Carcinoid Tumor; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Diarrhea; Exocrine Pancreatic Insufficiency; Female; Humans; Loperamide; Male; Middle Aged; Piperidines; Short Bowel Syndrome; Time Factors

Topics: Biopsy; Carbamates; Carcinoid Tumor; Cycloheptanes; Female; Histamine H1 Antagonists; Humans; Liver Neoplasms; Middle Aged; Piperidines; Pyridinium Compounds; Serotonin Antagonists; Thiophenes