peptide-yy and Carcinoid-Tumor

Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries.

Topics: Aged; Carcinoid Tumor; Chronic Disease; Constipation; Female; Humans; Ovarian Neoplasms; Ovariectomy; Ovary; Peptide YY

Primary carcinoid tumors are rare neoplasms of the ovary. Of the 4 histologic subtypes, ovarian carcinoid tumors with insular patterns produce carcinoid syndrome in approximately one third of cases, versus strumal and trabecular carcinoids which very rarely cause typical carcinoid syndrome. A unique presentation of ovarian carcinoid tumors with concurrent severe constipation has been reported, which is thought to represent a new carcinoid syndrome. The proposed mechanism is the production of peptide YY by the tumor, a gastrointestinal hormone responsible for decreasing gut motility. We report a case of a 34-yr-old white woman who presented with constipation and weight loss for 1 yr, and was found to have a unilateral ovarian strumal carcinoid, which produced peptide YY as demonstrated by immunohistochemistry. The 13 previous case reports of ovarian carcinoids with constipation are reviewed and the clinicopathologic features are discussed. This report and literature review further solidifies this entity as a new type of carcinoid syndrome.

Topics: Adult; Carcinoid Tumor; Comorbidity; Constipation; Female; Gastrointestinal Motility; Humans; Ovarian Neoplasms; Ovariectomy; Ovary; Peptide YY; Severity of Illness Index; Struma Ovarii; Syndrome; Treatment Outcome

Ovarian carcinoid is a rare tumor accounting for approximately 0.1% of all ovarian malignancies. We describe a case of peptide-YY-producing strumal carcinoid of the ovary associated with severe constipation. A 48-year-old woman was found to have a pelvic mass on ultrasonography when she visited her primary doctor for a health check-up. She was thus referred to our department. Magnetic resonance imaging revealed a solid right ovarian tumor 60 × 50 mm in size. The patient underwent a right adnexectomy and was histopathologically diagnosed as having strumal carcinoid of the ovary. On immunohistochemical examination, the tumor cells were positive for peptide YY. The patient's constipation resolved rapidly after surgery. Based on her clinical course, her constipation was considered to have been caused by the strumal carcinoid of the ovary. The clinical course of this case supports the previously recognized correlation between peptide-YY-producing ovarian carcinoid and constipation.

Topics: Carcinoid Tumor; Constipation; Female; Humans; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; Ovary; Peptide YY; Severity of Illness Index; Struma Ovarii

Peptide YY (PYY) is a naturally occurring gut hormone with mostly inhibitory actions on multiple tissue targets. PYY has been identified in several carcinoid tumors and a decreased expression of PYY may be relevant to the development and progression of colon adenocarcinoma. Treatment with PYY decreases growth in pancreatic and breast tumors, most likely through a reduction in intracellular cAMP. In cancer patients, PYY may also improve malnutrition that results from iatrogenic causes or cachexia associated with advanced disease. PYY plays a significant role in multiple aspects of cancer from regulation of cell growth to potential therapeutic applications.

Topics: Adenocarcinoma; Breast Neoplasms; Cachexia; Carcinoid Tumor; Cell Division; Colonic Neoplasms; Cyclic AMP; Humans; Pancreatic Neoplasms; Peptide YY; Time Factors

Topics: Carcinoid Tumor; Colon; Endocrine Glands; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Glucagon-Like Peptides; Humans; Nervous System; Neuropeptides; Neurosecretory Systems; Peptide PHI; Peptide YY; Peptides; Rectum; Vasoactive Intestinal Peptide

Primary ovarian carcinoid tumor is uncommon and represents less than 0.1% of ovarian malignancies. The strumal carcinoid may be complicated by carcinoid syndrome induced by peptide YY (PYY).. We describe a 45-year-old woman with a bilateral ovarian tumor diagnosed through periodical gynecological examination. She presented with severe constipation. Right ovarian cyst laparoscopically resected was diagnosed as a strumal carcinoid tumor; the left one was mature cystic teratoma. No metastatic findings were seen macroscopically on the ovarian surface and pelvic peritoneum. Constipation was drastically improved by resecting the tumor. The carcinoid tumor cells were positive for tumor-producing PYY by mRNA analysis.. It is important to be aware of this entity in the pathological diagnosis of ovarian tumors, in the presence of any clinical indicator of carcinoid tumor/syndrome, as it carries a markedly better prognosis and clinical outcome in comparison with most other malignant ovarian tumors.

Topics: Carcinoid Tumor; Female; Humans; Middle Aged; Ovarian Neoplasms; Peptide YY; RNA, Messenger; Struma Ovarii

Primary ovarian carcinoid tumors are rare. It has been reported that constipation was a presenting symptom in some patients with ovarian carcinoid. A case of strumal carcinoid of the ovary with contralateral clear cell adenocarcinoma of the ovary discovered with a complaint of constipation is described. Constipation was dramatically improved by resectioning the tumor. The tumor cells were positive for peptide YY (PYY) in the carcinoid component, but not in any other components. The present case could provide evidence of the correlation between constipation and PYY that has been reported elsewhere. Interestingly, the constipation caused by PYY also helped in discovering epithelial ovarian cancer.

Topics: Adenocarcinoma, Clear Cell; Carcinoid Tumor; Constipation; Female; Humans; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Ovary; Peptide YY

A case of a 58-year-old woman with ovarian carcinoid exhibiting double function is reported. She had suffered from constipation and hirsutism before surgery. Pathological examination revealed that many carcinoid tumor cells were immunohistochemically positive for peptide YY, which inhibits intestinal motility and many peripheral steroid cells. After surgery the patient recovered from constipation immediately. Although the serum level of testosterone also immediately decreased, hirsutism remained for about 2 years. These clinical manifestations are considered to be due to peptide hormone-producing tumor parenchymal cells and testosterone-producing functioning stromal cells. This is the first report of clinically manifested double-functioning ovarian carcinoid; one function is due to tumor cells themselves and another function is due to stromal cells.

Topics: Biomarkers, Tumor; Carcinoid Tumor; Constipation; Cytoplasmic Granules; Fallopian Tubes; Female; Hirsutism; Humans; Hysterectomy; Middle Aged; Neurosecretory Systems; Ovarian Neoplasms; Peptide YY; Testosterone; Treatment Outcome

Primary carcinoid tumor of the ovary is uncommon and represents less than 0.1% of ovarian malignancy. Recently, it was reported that the strumal carcinoid tumor may be complicated by severe constipation as one symptom of the carcinoid syndrome.. A 50-year-old nulliparous woman complained of persisting constipation and abdominal distention with pelvic mass, raising the possibility of ovarian tumor. The sugically resected tumor was diagnosed as strumal carcinoid tumor. Her long-lasting severe constipation completely disappeared after tumor removal but recurred with recurrent hepatic disease. The tumor cells were positive for PYY, a peptide hormone that has a strong inhibitory effect on intestinal motility, by immunohistochemical stain.. Our case provides the more convincing information to indicate that PYY protein, produced by ovarian tumor cells in the trabecular carcinoid component, may be associated with severe constipation.

Topics: Carcinoid Tumor; Constipation; Female; Humans; Middle Aged; Ovarian Neoplasms; Peptide YY

Functioning ovarian carcinoid tumors are well known to cause carcinoid syndrome. Recently, strumal and trabecular ovarian carcinoid tumors are reported to cause severe constipation possibly because of tumor-producing peptide YY (PYY). We studied a case of primary ovarian strumal carcinoid who had had severe constipation until the tumor was removed by surgical operation. Immunohistochemically, many tumor cells were strongly positive for PYY. By Northern blot and reverse transcription polymerase chain reaction analyses, PYY mRNA was expressed in a complete form as detected in normal human colon mucosa. From these findings, an ovarian strumal carcinoid is strongly suggested to express complete PYY mRNA and therefore complete PYY protein that results in severe constipation.

Topics: Blotting, Northern; Carcinoid Tumor; Constipation; Female; Humans; Immunohistochemistry; Middle Aged; Ovarian Neoplasms; Peptide YY; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Struma Ovarii

We report a patient with primary trabecular carcinoid of the ovary with severe constipation probably due to peptide YY production by the tumor. A 43-year-old female had complained of severe constipation for several months and was found to have a left ovarian tumor. The surgically resected tumor was diagnosed as trabecular carcinoid by light microscopic examination. The carcinoid tumor cells were intensely and uniformly stained by the Grimelius technique. Immunohistochemically, the tumor cells were strongly positive for peptide YY, which has a strong inhibitory action on intestinal motility. The patient has been free from constipation since the removal of the tumor. The present case supports previously reported findings that not typical carcinoid syndrome but rather severe constipation accompanies primary trabecular carcinoid of the ovary, and that peptide YY is presumably the cause of the constipation.

Topics: Adult; Carcinoid Tumor; Constipation; Female; Gastrointestinal Hormones; Humans; Ovarian Neoplasms; Peptide Biosynthesis; Peptide YY; Teratoma

Five patients with ovarian carcinoid who had severe constipation for a long period preoperatively showed marked reduction of this symptom postoperatively. Because this phenomenon was believed to be caused by some biologically active substance rather than a mechanical effect of the tumor, reactivity to 17 amine and peptide hormones was studied immunohistochemically in these patients. Numerous peptide YY (PYY)-positive cells were detected, with PYY-positive cells representing more than 50% of all carcinoid tumor cells in each patient. PYY, which has a pharmacologic inhibitory action on intestinal motility, was presumably the cause of the constipation in these patients.

Topics: Adult; Aged; Carcinoid Tumor; Constipation; Female; Gastrointestinal Motility; Humans; Immunohistochemistry; Middle Aged; Ovarian Neoplasms; Peptide Biosynthesis; Peptide YY

A case of ovarian carcinoid tumor of the trabecular type is presented. The small carcinoid tumor was found incidentally in a resected dermoid cyst. Histologically, the tumor was surrounded by a smooth muscle layer with focal stromal invasion. Non-carcinoid papillary mucosa and a few small glands, simulating the mucosa of the fallopian tube and remnant müllerian glands, respectively, were also present adjacent to the carcinoid tumor and enclosed by the same smooth muscle layer. The tumor cells revealed argyrophilia, and were positive for peptide tyrosine tyrosine (PYY) in the cytoplasm and for CEA in part of the luminal surface. This case was considered to be a rare ovarian carcinoid tumor arising from a dermoid cyst, without association of struma ovarii. PYY may be a potential marker for determining the histogenesis of ovarian carcinoid tumors.

Topics: Adult; Carcinoembryonic Antigen; Carcinoid Tumor; Dermoid Cyst; Female; Humans; Immunohistochemistry; Neoplasms, Multiple Primary; Ovarian Neoplasms; Peptide YY; Peptides

The Mastomys (Praomys natalensis) species are a unique natural model in which the bioactivity of gastric carcinoids may be studied. Several investigators have previously demonstrated that these tumors contain large amounts of histamine. In this study we investigated the presence of peptides associated with the neoplasm. The levels and location of gastrin, gastric inhibitory peptide (GIP), neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), glucagon, bombesin, vasoactive intestinal peptide (VIP) and somatostatin (SRIF) were investigated by radioimmunoassay and immunocytochemistry. In addition the distribution of these peptides were evaluated in the gastrointestinal tract of young and old animals to investigate possible age-related changes. PYY and enteroglucagon (EG) were significantly (P less than 0.001) elevated in both tumor tissue (676 +/- 152, 551 +/- 164 pmol/g) and plasma (620 +/- 160, 500 +/- 147 pmol/l) of tumor-bearing animals. Immunocytochemistry revealed PYY- and EG-like immunoreactivity in 20-30% of tumor cells. A significant decrease (P less than 0.05) in bombesin was noted in older animals, but no changes in gastric tissue content of PYY or EG could be detected between young and old animals. Gastrin was not detected in tumors and there were no significant changes in tissue or plasma levels with age. Small bowel concentrations of VIP and PYY were higher in the older mastomys (P less than 0.05). In contrast, colonic levels of bombesin, VIP, somatostatin and PYY were significantly lower (P less than 0.05) in older mastomys compared with young. The age-related changes in several peptides may reflect an adaptive response to acid hypersecretion. The multi-hormonal character of these neoplasms suggests that these tumors develop from a pluripotential stem cell.

Topics: Age Factors; Animals; Bombesin; Carcinoid Tumor; Gastric Inhibitory Polypeptide; Gastrins; Immunohistochemistry; Muridae; Neoplasm Proteins; Neurotensin; Pancreatic Polypeptide; Peptide YY; Peptides; Radioimmunoassay; Stomach Neoplasms; Vasoactive Intestinal Peptide

Carcinoid tumours from man and Mastomys (Praomys) natalensis produce a variety of peptide hormones. The study of these peptide-secreting tumours has been difficult because of the small amount of tissue available and because of limitations with present cell culture systems. The aim of this study was to establish an experimental model where carcinoid tumours could be maintained and their hormone secretion studied. The intra-ocular transplantation technique was chosen for its simplicity and high rate of success. Gastric carcinoid tumours from mastomys (n = 4) and human carcinoids (n = 2) (one bronchial and one ileal) were transplanted to the anterior eye chamber of Sprague-Dawley rats. Pieces of fresh tumour tissue were injected into the anterior eye chamber of rats and allowed to grow for 4-8 weeks. Rats transplanted with human tissue were immunosuppressed by daily injections with cyclosporin A (20 mg/kg). Eye chambers were inspected regularly and plasma from transplanted rats was collected for assay of peptide YY (PYY) and glucagon. Vascularization of transplants occurred within 1-2 days after transplantation in 70-80 per cent of all experiments. Microscopic analysis of transplants demonstrated a rich supply of blood vessels to tumour cells which contained characteristic neurosecretory granules. Transplanted rats had significantly (P less than 0.05) elevated levels of PYY (44-165 pmol/l) and glucagon (67-162 pmol/l) in plasma as compared with sham-operated rats (PYY 28-40 pmol/l, glucagon 33-40 pmol/l), indicating that hormone secretion by tumour cells in oculo was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Carcinoid Tumor; Eye Neoplasms; Gastrointestinal Hormones; Glucagon; Humans; Male; Muridae; Neoplasm Transplantation; Peptide YY; Peptides; Rats; Rats, Inbred Strains

Gastric carcinoid tumor formation has been reported with prolonged achlorhydria in both animals and human beings. The hypothesis in this study was that the ablation of parietal cell function in an animal (mastomys) genetically predisposed to gastric neuroendocrine neoplasia would promote and accelerate tumor formation. Loxtidine, an irreversible H2-receptor blocker, was administered at 1 mg/kg/day in drinking water for 4 months to young mastomys (n = 16). After 4 months of treatment, 14 of 16 animals had gastric carcinoids compared with 0 of 16 young control animals and 4 of 16 older control animals. Ultrastructurally, these tumors were characterized by the presence of neurosecretory granules. Serum gastrin levels were elevated (230 +/- 40 pmol/L) in loxtidine-treated animals compared with control animals (26 +/- 8 pmol/L) (p less than 0.05). In addition, both peptide YY (620 +/- 160 pmol/L) and enteroglucagon (500 +/- 147 pmol/L) were significantly elevated compared with control groups (p less than 0.05). Similarly, in tumor tissue, peptide YY (676 +/- 152 pmol/gm) and enteroglucagon (551 +/- 164 pmol/gm) were found in large quantities, whereas gastrin was undetectable. These observations provide substantial support for the possible pathophysiologic role of gut peptides, particularly gastrin, in the generation of endocrine neoplasia. The advent of endocrine tumors after inhibition of a gut secretory cell (parietal) may be of considerable significance in understanding the genesis of endocrine neoplasia. Whether the drug acts as a neoplastic promoter of enterochromaffin-like cells or the tumor development is related to elevation of peptides such as gastrin cannot be established in this study. Long-term H2-receptor blockade with new potent, irreversible agents as an alternative to surgery may have potential grave implications that require careful consideration.

Topics: Animals; Carcinogens; Carcinoid Tumor; Gastric Mucosa; Gastrointestinal Hormones; Glucagon-Like Peptides; Histamine H1 Antagonists; Hyperplasia; Muridae; Peptide YY; Peptides; Reference Values; Stomach; Stomach Neoplasms; Triazoles

Glucagon/PP-related peptides were detected immunohistochemically in 18 out of 22 cases of rectal tumors investigated. The reactive tumors showed prevalence of trabecular or mixed trabecular-acinar structure and moderate staining with Grimelius' silver and lead-hematoxylin. Three of the remaining 4 cases were characterized by reactivity for 5-hydroxytryptamine only, prevalence of a solid nest structural component and intense staining with Grimelius' silver technique and lead-hematoxylin. Fifteen of the 18 glucagon/PP-reactive cases were investigated immunohistochemically with a series of 6 sera directed against different sequences of glucagon, glicentin and proglucagon, and of 7 sera directed against PP, PYY and proPP-icosapeptide. A large spectrum of glucagon-related immunoreactivities, including C-terminus and mid-portion glucagon-immunoreactivity, N- and C-terminus glicentin-immunoreactivity, GLP1- and GLP2-immunoreactivity, were detected in human rectal L cells and most rectal carcinoids. With the exception of a few scattered cells in the rectal mucosa and in 3 tumors, C-terminus glucagon-immunoreactivity was obtained only after trypsin or subtilisin treatment of tissue sections. Both PYY and PP/proPP-like peptide(s) were detected in rectal L cells and carcinoids, with prevalence of PYY in normal cells and PP/proPP-like peptides in tumor cells. It is concluded that the same or closely related hormone/prohormone sequences are synthesized and stored in rectal endocrine cells and carcinoid tumors although differences of quantitative expression, post-translational cleavage or reactivity to antibodies may occur. The usefulness of protease treatments of tissue sections to unmask immunoreactivities of uncleaved propeptides or fixative-denatured peptides is outlined.

Topics: Animals; Carcinoid Tumor; Cattle; Glucagon; Humans; Immunologic Techniques; Neurotensin; Pancreatic Polypeptide; Peptide YY; Peptides; Proglucagon; Protein Precursors; Rectal Neoplasms; Serotonin; Somatostatin

The distribution and frequency of peptide YY (PYY) cells in 60 gastrointestinal carcinoids and in the nonneoplastic mucosa around the carcinoids were studied by an indirect immunoperoxidase method with anti-PYY serum. Additionally, the endocrine cell type of the PYY cells in appendiceal and rectal carcinoids was assessed by transmission electron microscopy. A few PYY cells were present in specimens of nonneoplastic mucosa from stomach, duodenum, jejunum, ileum, and appendix, with an abundance of these cells in rectal mucosa. Peptide YY cells were found in one of 13 gastric, one of 13 duodenal, one of one jejunal, zero of two ileal, three of 11 appendiceal, and 16 of 20 rectal carcinoids. All but one of the PYY-positive carcinoids were argyrophil carcinoids. Peptide YY cells in the gastric, duodenal, and jujunal carcinoids were present in small numbers. The three PYY-positive carcinoids of the appendix were composed almost totally of PYY cells, whereas those of the rectum generally contained only sporadic PYY cells. The peptide YY cells observed ultrastructurally contained almost round secretory granules (about 160 nm in average diameter), which were most consistent with D1(H) cell type granules with respect to shape and average diameter. This is the first systematic immunohistochemical and ultrastructural study of PYY cells in gastrointestinal carcinoids.

Topics: Carcinoid Tumor; Gastric Mucosa; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunochemistry; Intestinal Mucosa; Microscopy, Electron; Peptide YY; Peptides

The frequency and distribution of polypeptide YY (PYY) and pancreatic polypeptide (PP) immunoreactive tumour cells of 14 small intestinal and of 27 rectal carcinoids were studied. All small intestinal and 14 rectal tumours were unreactive to both hormones. However, 13 rectal carcinoids contained a variable number of PP-immunoreactive cells. In four of these cases both PYY- and PP-immunoreactive cells were seen. The PP-immunoreactive cells greatly exceeded the number of PYY-immunoreactive cells. Two rectal carcinoids with PYY and PP immunoreactivities, but not the rest of the tumours, reacted also with an antiserum specific to the C-terminus of PP. This indicates that most PP immunoreactive rectal carcinoids lack the C-terminus sequence of the PP molecule.

Topics: Carcinoid Tumor; Histocytochemistry; Humans; Immunologic Techniques; Intestinal Neoplasms; Intestine, Small; Pancreatic Polypeptide; Peptide YY; Peptides; Rectal Neoplasms