vasoactive-intestinal-peptide and Rectal-Neoplasms

Topics: Appendiceal Neoplasms; Carcinoid Tumor; Carcinoma, Small Cell; Cholecystokinin; Digestive System; Duodenum; Endocrine Glands; Fetus; Gastric Mucosa; Gastrins; Humans; Ileum; Peptides; Rectal Neoplasms; Respiratory System; Secretin; Substance P; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) is known to cause the watery diarrhea, hypokalemia, and achlorhydria syndrome. A 14-year-old girl was admitted with a 4-year history of persistent uncontrollable diarrhea and hypokalemia. Computed tomographic evaluation of the neck, chest, and abdomen were normal. Numerous polyps covering the entire colon and rectum were noted on colonoscopy. The serum VIP level was 143 pg/mL. The patient underwent a total proctocolectomy with an ileal-J-pouch. The pathologic examination revealed ganglioneuromatosis. Postoperatively, the symptoms resolved, and the serum VIP level fell to lower than 5 pg/mL. This is an unusual case of the watery diarrhea, hypokalemia, and achlorhydria syndrome caused by ganglioneuromatosis of the entire colon and rectum.

Topics: Adolescent; Colonic Neoplasms; Colonic Pouches; Female; Ganglioneuroma; Humans; Proctocolectomy, Restorative; Rectal Neoplasms; Vasoactive Intestinal Peptide

The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) mediate physiologic activities in the intestine, not least in relation to motility and inflammatory processes. Neuropeptides are up-regulated and play particular importance during tissue stress. This paper aims to quantify mucosal and smooth muscle SP, VIP and total innervation in human colon in short- and long-term perspectives after abdominal irradiation.. Colon specimens from 23 irradiated or non-irradiated patients were investigated with immunohistochemistry and computerized image analysis. Plasma levels of SP and VIP in 15 additional patients receiving radiotherapy were analyzed.. At 4-7 days after irradiation (5 x 5 Gy), the overall innervation, and also VIP and SP nerve fiber densities, were increased in both mucosa and circular muscle layer. In contrast, 5-6 weeks as well as several years after irradiation, the VIP and SP nerve fiber densities were decreased. No peptide changes were revealed in plasma.. The degree of VIP and SP intestinal innervation was increased after radiotherapy in the short-term perspective but it decreased in the long-term. In the short-term, SP may have pro-inflammatory and VIP anti-inflammatory effects and the peptides may have trophic effects and be related to the occurrence of motor changes. It cannot be excluded that the decrease in VIP and SP neuronal supply seen in the long-term may contribute to intestinal malfunction.

Topics: Abdomen; Aged; Carcinoma; Cell Count; Colon; Colonic Neoplasms; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Muscle, Smooth; Nerve Fibers; Neurons; Pelvis; Radiation Dosage; Radioimmunoassay; Rectal Neoplasms; Substance P; Thiolester Hydrolases; Time; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

It is not clear what contribution the internal anal sphincter makes to the impaired motility observed in patients with Hirschsprung's disease (HD). Neuropeptides have recently been shown to be neurotransmitters in the nonadrenergic, noncholinergic inhibitory and excitatory nerves in the human gut. To clarify the physiologic significance of vasoactive intestinal polypeptide and substance P in the internal anal sphincter of HD (aganglionosis), we investigated the enteric nerve responses on lesional and normal internal anal sphincter muscle strips above the dentate line.. The lesional and normal internal anal sphincter muscle strips above the dentate line were derived from patient with HD (9 cases) and patients who underwent rectal amputation for low rectal cancers (8 cases). A mechanographic technique was used to evaluate in vitro muscle responses to these peptides of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers.. Nonadrenergic, noncholinergic inhibitory nerves were found to act on the normal internal anal sphincter but had no effect on the enteric nerves in aganglionosis. Peptidergic (vasoactive intestinal polypeptide and substance P) nerves were found to act on normal colon, but no effect was observed in the aganglionic internal anal sphincter.. These findings suggest that peptidergic nerves play an important role in the impaired motility observed in the internal anal sphincter with HD.

Topics: Aged; Anal Canal; Atropine; Electric Stimulation; Female; Ganglia, Autonomic; Gastrointestinal Motility; Hirschsprung Disease; Humans; In Vitro Techniques; Infant; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Phenoxybenzamine; Propranolol; Rectal Neoplasms; Substance P; Tetrodotoxin; Vasoactive Intestinal Peptide

Recent studies have shown that various gastrointestinal tumours express substantial amounts of vasoactive intestinal peptide (VIP) receptors. Based on these observations, we have developed a receptor scintigraphy using [123I]VIP as a radioligand. An initial series performed at our institution showed promising potential for visualization of various gastrointestinal adenocarcinomas by means of [123I]VIP. In this article, we now report the results obtained in 80 consecutive patients with colorectal adenocarcinoma. Eighty consecutive patients with histologically verified colorectal cancer underwent scanning by means of [123I]VIP (1 microg, approximately 150 MBq). Thirteen patients were free of tumour after complete resection of Dukes' C cancer, eight patients presented with primary and 14 with locally recurrent tumours but were free of metastases. Ten patients had locally recurrent disease and liver, lung or lymph node metastases. Disease confined to organ metastases (i.e. liver, lung or lymph nodes) was present in 35 patients. The size of the primary or recurrent tumours ranged between 3 and 6 cm, and the size of metastases was between 1 and 13 cm in diameter. Scan results were evaluated independently by two nuclear medicine physicians in a blinded way, and results were then compared with computerized tomography (CT)scans not older than 4 weeks. Seven out of eight primary (87%) and 21 out of 24 (82%) locally relapsing cancers were imaged with [123I]VIP. Negative VIP scans were obtained in all 13 patients in whom the cancers had been curatively resected. All patients with lymph node metastases showed positive VIP scans (four out of four), and positive scans were obtained in 25 out of 28 (89%) patients with liver metastases and in two out of three cases with lung metastases. In four patients with relapsing cancer, the VIP scan indicated the presence of disease before CT, and in two patients the diagnosis of scar tissue instead of a local recurrence of rectal cancer as suggested by CT could be established. We conclude that [123I]VIP receptor scanning is a sensitive method for radioimaging of colorectal cancer with the potential to provide valuable additional information to conventional radiological methods.

Topics: Adult; Aged; Colonic Neoplasms; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Tomography, Emission-Computed, Single-Photon; Vasoactive Intestinal Peptide

The purpose of this study was to investigate the peculiarities of hormonal regulation of adenylate cyclase (AC) of blood lymphocytes in colorectal cancer patients and to compare these peculiarities with hormone sensitivity of AC of colorectal tumors and normal colonic mucosa. Basal and stimulated lymphocyte AC activity was studied in 51 healthy persons and 52 cancer patients (14 with colon cancer, 21 with rectal cancer and 17 with stomach cancer) aged 20-75 years. In 31 of 35 patients with colorectal cancer the AC activity was studied simultaneously in lymphocytes, tumor tissue and normal colonic mucosa. To evaluate basal and stimulated AC activity the measurement of c-AMP (Amersham kits) formed in the presence of ATP regenerating system was used. Basal and by VIP, pentagastrin and sodium fluoride stimulated AC activity in lymphocytes of gastrointestinal cancer patients was lower than in lymphocytes of healthy subjects of similar age. Stage dependence of the parameters under study was not found. There was a tendency for higher basal and stimulated lymphocyte AC activity in colon cancer patients as compared to stomach and rectal cancer patients. In colorectal cancer patients the peculiarities of lymphocyte AC reactions to stimulation were closer to those in tumor tissue but not to those in normal colonic mucosa. The reaction of lymphocyte AC to VIP and glucagon coincided more frequently with tumor AC reactions to the same hormones in case of hormone nonsensitive tumors. Thus, basal and stimulated lymphocyte AC activity in colorectal cancer patients was modified to some degree by tumor factors. Lymphocyte AC reactions to VIP and glucagon may be considered as indirect markers of hormone sensitivity of colonic tumors. Moreover, the probability of discovery of hormone nonsensitive tumors by this way is more reliable than hormone sensitive ones.

Topics: Adenosine Triphosphate; Adenylyl Cyclases; Adult; Aged; Calcitonin; Colonic Neoplasms; Epinephrine; Glucagon; Humans; Intestinal Mucosa; Lymphocytes; Middle Aged; Pentagastrin; Rectal Neoplasms; Sodium Fluoride; Stomach Neoplasms; Vasoactive Intestinal Peptide

Our goal was to define the incidence of neuroendocrine carcinomas of the colon and rectum, the patterns of neuroendocrine expression, and the cellular subtype within neuroendocrine tumors. We attempted to determine whether differences in neuroendocrine expression or specific cell type influenced survival.. Over a ten-year period, 988 patients had resections for colorectal cancer. Using immunohistochemical staining methods specific for neuroendocrine markers, 39 (3.9 percent) neuroendocrine cancers were identified retrospectively. Tumors were also stained with monoclonal antibody A-80 which is specific for exocrine differentiation. In this way we were able to determine the extent of neuroendocrine differentiation such as pure neuroendocrine, predominant neuroendocrine, and equal neuroendocrine-exocrine expression.. Average patient age was 65.5 (range, 28-89) years; there were 25 males and 14 females. Nineteen tumors were located in the right colon, 11 in the left, and 9 were in the rectum. Three histopathologic patterns were identified: pure neuroendocrine (n = 11), predominantly neuroendocrine (n = 17), and cancers with equal exocrine and neuroendocrine differentiation (n = 7). Three cellular subtypes were seen: small-cell (n = 15), intermediate-cell (n = 15), and well-differentiated neuroendocrine cancers (n = 5). There was one Dukes A cancer, 7 Dukes B, 16 Dukes C, and 15 patients had metastases to distant sites at the time of diagnosis. As a group, neuroendocrine tumors have a poor prognosis: six-month survival was 58 percent, three-year survival was 15 percent, and five-year survival was 6 percent. Survival statistically correlated with tumor stage (P = 0.01) but not with age, sex, tumor location, histopathologic pattern, or neuroendocrine subtypes. Median survival for pure neuroendocrine carcinomas was seven months and for predominantly neuroendocrine carcinomas was five months. Tumors with equal neuroendocrine and exocrine differentiation had a median survival of 22 months (P = 0.3). Small-cell neuroendocrine carcinomas had a median survival of five months, intermediate-cell had 11 months, and well-differentiated had a median survival of 22 months (P = 0.1).. Neuroendocrine differentiation is found in at least 3.9 percent of colon and rectal cancers. Many of these tumors were initially diagnosed as "carcinoids," the diagnosis was changed to "neuroendocrine carcinoma" after immunohistochemical staining. Overall survival is poor especially for small-cell and pure neuroendocrine carcinomas.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Colonic Neoplasms; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Phosphopyruvate Hydratase; Rectal Neoplasms; Serotonin; Survival Rate; Time Factors; Vasoactive Intestinal Peptide

This report describes a 7-year-old boy presenting with watery diarrhea, hypokalemia, and hypochlohydria associated with vasoactive intestinal polypeptide (VIP)-secreting ganglioneuromatosis involving the entire colon and rectum. The child's symptoms resolved following proctocolectomy, and the VIP levels returned to normal. Although 55 previous children have been reported with VIP-secreting tumors, this case is the first involving the entire colon and rectum.

Topics: Adenoma, Islet Cell; Child; Colonic Neoplasms; Ganglioneuroma; Humans; Male; Rectal Neoplasms; Vasoactive Intestinal Peptide; Vipoma

Topics: Adenocarcinoma; Casein Kinases; Cell Line; Colonic Neoplasms; Cyclic AMP; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Gastrointestinal Hormones; Humans; Phosvitin; Protamine Kinase; Protein Kinases; Rectal Neoplasms; Subcellular Fractions; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP), secretin, catecholamines and prostaglandin E1 (PGE1) in the presence of a cyclic nucleotide phosphodiesterase inhibitor stimulate the accumulation of cyclic AMP in two colorectal carcinoma cell lines (HT 29 and HRT 18) with subsequent activation of the cyclic AMP-dependent protein kinases. In HT 29 cells incubated without phosphodiesterase inhibitor, 10(-9) M VIP promotes a rapid and specific activation of the lower Km cyclic AMP phosphodiesterase (1.7-fold); at 25 degrees C the effect is maintained for more than 15 min, while at 37 degrees C the activity returns to basal value within 15 min. As shown by dose-response studies, VIP is by far the most effective inducer (Ka equals 4 x 10(-10) M) of the cyclic AMP phosphodiesterase activity; partial activation of the enzyme is obtained by 3 x 10(-7) M secretin, 10(-5) M isoproterenol and 10(-5) M PGE1; PGE2 and epinephrine are without effect. In HRT 18 cells VIP is less active (Ka equals 2 x 10(-9) M) whereas 10(-6) M PGE1, 10(-6) M PGE2 and 10(-5) M epinephrine are potent inducers of th phosphodiesterase activity. The positive cell response to dibutyryl-cyclic AMP further indicates that cyclic AMP is a mediator in the phosphodiesterase activation process. The incubation kinetics and dose response effects of the various agonists on the cyclic AMP-dependent protein kinase activity determined for both cell types in the same conditions show a striking similarity to those of phosphodiesterase. Thus coordinate regulation of both enzymes by cyclic AMP was observed in all incubation conditions.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenocarcinoma; Animals; Bucladesine; Catecholamines; Cells, Cultured; Colonic Neoplasms; Cyclic AMP; Enzyme Activation; Gastrointestinal Hormones; Prostaglandins E; Protein Kinases; Rectal Neoplasms; Secretin; Vasoactive Intestinal Peptide

This study was undertaken to assess the role of vasoactive intestinal peptide (VIP) in the control of cyclic adenosine 3':5'-monophosphate production in colonic tumor cells. Seven human colorectal adenocarcinoma cell lines in culture were investigated (HT-29, HRT-18, SW-480, Caco-2, CO-115, CO-125, and HCT-8R). These cell-lines had a cyclic adenosine 3':5'-monophosphate production system which was very sensitive to VIP but less so to prostaglandin E1 and/or isoproterenol. Nonintestinal human malignant epithelial cells, such as HeLa (cervix) and Caki-1 and Caki-2 (kidney), by contrast, did not respond to VIP. The dose-response relationships of malignant colorectal cells were compared to those obtained with epithelial cells of normal human colon and showed that: (a) maximal responses were observed with 0.1 micro M VIP in both malignant and normal cells; (b) half-maximal responses were elicited by VIP concentrations in the 0.3 to 2 nM range in malignant cells (1.2 nM in normal cells), thus indicating the high apparent affinity of the cells to VIP; and (c) the magnitudes of the responses (stimulated:basal ratios) were highly variable in malignant cells, ranging from 225 in HT-29 cells to 3.5 in Caco-2 cells, but were more constant, in the order of 25, in normal cells. Secretin, a VIP agonist in intestinal tissue, stimulated cyclic adenosine 3':5'-monophosphate accumulation in all colorectal cells, but with a 1000- to 5000-fold lower potency than did VIP. These results show that the VIP-sensitive adenylate cyclase system operates in malignant as well as in normal colon epithelial cells.

Topics: Adenocarcinoma; Adenylyl Cyclases; Animals; Cell Line; Colonic Neoplasms; Cyclic AMP; Gastrointestinal Hormones; HeLa Cells; Humans; Isoproterenol; Mice; Neoplasms, Experimental; Prostaglandins E; Rectal Neoplasms; Vasoactive Intestinal Peptide