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A 38-year-old Japanese man who had been diagnosed with appendiceal carcinoid and undergone ileocecal resection 8 years before presented with duodenal obstruction caused by a submucosal tumor-like appearance. He was diagnosed with long-term recurrence of appendiceal goblet cell carcinoid (GCC) with a multi-morphological pattern based on the histological assessment of a duodenal biopsy and his previously resected appendix. He underwent subtotal stomach-preserving pancreaticoduodenectomy combined with resection of an ileo-colic anastomotic lesion. The GCC recurred at the nearby ileo-colic anastomosis and invaded the duodenum. This late recurrence might have resulted from the unique features of his GCC, which contained cells with different degrees of malignancy.

Background: Sudden massive release of serotonin, histamine, kallikrein, and bradykinin is postulated to cause an intraoperative carcinoid crisis. The exact roles of each of these possible agents, however, remain unknown. Optimal treatment will require an improved understanding of the pathophysiology of the carcinoid crisis., Methods: Carcinoid patients with liver metastases undergoing elective abdominal operations were studied prospectively, using intraoperative, transesophageal echocardiography, pulmonary artery catheterization, and intraoperative blood collection. Serotonin, histamine, kallikrein, and bradykinin levels were analyzed by enzyme-linked immunosorbent assay., Results: Of 46 patients studied, 16 had intraoperative hypotensive crises. Preincision serotonin levels were greater in patients who had crises (1,064 vs 453 ng/mL, P = .0064). Preincision hormone profiles were otherwise diverse. Cardiac function on transesophageal echocardiography during the crisis was normal, but intracardiac hypovolemia was observed consistently. Pulmonary artery pressure decreased during crises (P = .025). Linear regression of preincision serotonin levels showed a positive relationship with mid-crisis cardiac index (r = 0.73, P = .017) and a negative relationship with systemic vascular resistance (r=-0.61, P = .015). There were no statistically significant increases of serotonin, histamine, kallikrein, or bradykinin levels during the crises., Conclusion: The pathophysiology of carcinoid crisis appears consistent with distributive shock. Hormonal secretion from carcinoid tumors varies widely, but increased preincision serotonin levels correlate with crises and with hemodynamic parameters during the crises. Statistically significant increases of serotonin, histamine, kallikrein, or bradykinin during the crises were not observed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A 64-year-old male former smoker with a history of prostate cancer presented to our pulmonary clinic, complaining of nonproductive cough for 10 years. Prior evaluation included treatment for upper airway cough syndrome and gastroesophageal reflux, stopping angiotensin-converting enzyme inhibitor, and initiation of inhaled β-agonists. Esophageal pH monitoring indicated silent reflux, and proton pump inhibitor therapy was started. He continued to cough and complain of dyspnea. Physical examination produced unremarkable results, with no evidence of lymphadenopathy. Pulmonary function tests showed a pseudo-restrictive pattern with air trapping, hyperreactivity, and incomplete bronchodilator responsiveness: FEV1, 2.48 L (69% of predicted); FVC, 3.57 L (75% of predicted); FEV1/FVC, 92%; total lung capacity, 7.00 L (100% of predicted); and residual volume, 3.05 L (136% of predicted). Laboratory studies, including a complete metabolic panel, prostate-specific antigen test, and complete blood count, yielded normal results., (Published by Elsevier Inc.)

Central sensitization defines a state of amplified sensory input within the nervous system across many organ systems; it overlaps syndromes as fibromyalgia, chronic fatigue, irritable bowel, and interstitial cystitis. Commonly, individuals will experience multiple syndromes during the course of their lifetime. A 62-year-old patient presented for evaluation of multiple medically unexplained symptoms postsurgically including chronic left chest wall and flank pain with concomitant diarrhea, abdominal pain, and facial flushing. After extensive multidisciplinary evaluations, he was diagnosed as having central sensitization in which the initial presentation mimicked carcinoid syndrome. He was subsequently treated with extensive multidisciplinary pain rehabilitation, and it did well.

The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours.In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term "DIPNECH syndrome" be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome., (Copyright ©ERS 2016.)

A case study of 35-year-old woman with persistent breathlessness and wheezing that had been unsuccessfully treated with inhaled beta 2-agonists and steroids for about two years. Patient developed dry cough and haemoptysis, so investigated further. Spirometry demonstrated a restrictive pattern. Chest CT demonstrated well defined hyperdense lesion in right middle lobe. Biopsy taken from the mass during bronchoscopy demonstrated the picture of atypical bronchial carcinoid. In this case, due to the lack of awareness, diagnosis of carcinoid was delayed by two years.

A 46-year-old woman with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion caused by primary ovarian mature teratoma with carcinoid components was presented in our case. The patient manifested sustained hypercortisolemia without circadian rhythm and a lack of suppression of either low-dose dexamethasone suppression test (LDDST) or high-dose dexamethasone suppression test (HDDST). There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumors led to sharp reduction of serum ACTH and cortisol concentrations. Immunohistochemistry showed positivity in CgA, Syn, CK, NSE. To the best of our knowledge, there are rare reports of an ACTH-secreting carcinoid components located in an ovarian mature teratoma, and bilateral ovarian mature teratoma makes it rarer.

Background: Carcinoid tumors are uncommon neuroendocrine tumors that account for less than 1% of gastrointestinal tract malignancies. They have a reported incidence of 1.3 per 100,000. Small bowel carcinoids are the commonest and have the highest incidence of associated second primary malignancies, followed by appendiceal and colorectal carcinoids. The most common second primary malignancy is colorectal adenocarcinoma., Case Series: We report a series of 11 patients observed in the period 2006-2011 with primary gastrointestinal tract cancers and synchronous carcinoids discovered incidentally by the histopathologist in the resected primary cancer specimen., Results: In all patients with synchronous carcinoids and colorectal adenocarcinoma there was a pattern of similar embryonic visceral origin. Is this a paracrine effect from biological peptides produced by the carcinoids?

Purpose: Carcinoid crises are rare life-threatening events involving cardiac instability when carcinoid tumours release vasoactive peptides. Such events can occur in the perioperative setting. Octreotide, a somatostatin analogue, is administered as a bolus dose of 100-500 μg iv or by infusion to treat carcinoid crises. Due to the apparent low risk-to-benefit profile, a much higher dose is sometimes used in urgent situations. The purpose of this study was to assess the evidence for administering doses or hourly infusions of octreotide that exceeded 1,500 μg iv to treat carcinoid crises. We also sought to identify which patients may require large doses and to describe the adverse effects of such doses., Source: We systematically searched Medline, EMBASE, and Cochrane databases and hand-searched reference lists of relevant articles in 2006 and again in 2010 and 2011. All study designs were included in our search. Resolution of crisis symptoms was the primary outcome., Principal Findings: Eighteen articles were included. No patient died during a carcinoid crisis. A retrospective chart review of 89 patients with carcinoid heart disease reported octreotide doses of 25-54,000 μg to treat carcinoid crises, although neither crisis symptoms nor outcomes were described., Conclusion: In the included case reports, carcinoid crises were managed effectively using octreotide 25-500 μg iv. Previous exposure to octreotide and carcinoid heart disease may warrant the need for higher doses. In addition to the low quality of the articles and the small sample size, inconsistent use of the term "carcinoid crisis" and paucity of reported outcomes were also limitations of this systematic review. These findings highlight the need for further investigation into dose-response relationships of octreotide for the treatment of carcinoid crisis.

Type I gastric carcinoids are indolent lesions that only rarely metastasize. Until now, lymph node metastasis had only being observed in large (≥10 mm) and usually invasive lesions (deep submucosa or beyond). This study reports a diminutive (8 mm) gastric carcinoid, limited to the superficial layer of the submucosa (sm1), with no angiovascular invasion, but with a high Ki-67 index (7%) and an involved perigastric lymph node. The aggressive behavior of this lesion ends the previous believe that small and superficial type I gastric carcinoids do not metastasize. This case also indicates that better parameters are necessary to evaluate the malignant potential of these lesions and presents a further support to the value of 2010 World Health Organization classification of gastrointestinal neuroendocrine tumors.

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., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Ectopic ACTH production causes 10% of Cushing's syndromes. The diagnostic workup is difficult, can last more than 6 months (> 50% of cases), and the underlying tumour is still frequently not located (12%). Carcinoid tumours of the appendix are frequent and are revealed in 0.3% of patients undergoing routine appendectomy. However, neuroendocrine tumours of the appendix with ACTH production are an extremely rare entity. Here we report the case of a female patient with clinically overt Cushing's syndrome due to ectopic ACTH-production from a carcinoid tumour of the appendix. During the diagnostic workup, repeated endocrine tests, multiple different imaging modalities and frequent and lengthy hospitalisations were necessary. Wrongly, even a neurosurgical pituitary exploration was performed. After 12 months from the initial admission, the tumour was finally detected by an ¹⁸F-fluoro-L-dihydroxyphenylalanine (¹⁸FDOPA PET) and an appendectomy followed by right hemicolectomy were performed. The patient recovered rapidly and the symptoms from the hypercortisolism were no more present.In this case, we discuss the multitude of problems, which may delay the diagnosis and the pitfalls, that should be avoided in order to locate the tumour and to initiate adequate therapy as early as possible. Furthermore, our case demonstrates the complexity of diagnostic procedures, which demand most of the times a multidisciplinary approach. In this setting, regular follow-ups in short time intervals and the use of novel imaging techniques can finally cut the diagnostic "Gordian knot"., (© J. A. Barth Verlag in George Thieme Verlag KG Stuttgart · New York.)

Gastric carcinoid tumors comprise 7% of all gastrointestinal carcinoids and have significantly increased in incidence over the past few decades. Seventy to 80% of gastric carcinoids are type I, which usually are clinically asymptomatic and found incidentally at endoscopic evaluation for abdominal pain or anemia. In this review, advances in understanding the pathophysiology of type I gastric carcinoid are highlighted. In addition, various current diagnostic and treatment options are discussed. Although type I carcinoids generally hold a benign course, rigorous investigation is needed to ensure accurate diagnosis and optimal treatment. This includes appropriate diagnostic procedures and imaging and accurate staging of tumor. Tumor size, depth of invasion, presence of metastasis, and the tumor's gastrin dependency dictate treatment options. Appropriate treatments can consist of endoscopic resection, antrectomy, medical management, or frequent follow-up. This article provides a systematic method of evaluating and treating type I gastric carcinoid.

Proton pump inhibitors have an excellent safety profile and have become one of the most commonly prescribed class of drugs in primary and specialty care. Long-term, sometimes lifetime, use is becoming increasingly common, often without appropriate indications. This paper is a detailed review of the current evidence on this important topic, focusing on the potential adverse effects of long-term proton pump inhibitor use that have generated the greatest concern: B12 deficiency; iron deficiency; hypomagnesemia; increased susceptibility to pneumonia, enteric infections, and fractures; hypergastrinemia and cancer; drug interactions; and birth defects. We explain the pathophysiological mechanisms that may underlie each of these relationships, review the existing evidence, and discuss implications for clinical management. The benefits of proton pump inhibitor use outweigh its risks in most patients. Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from long-term therapy.

Gastric carcinoid tumors are rare, but are increasing in incidence. This article reviews what is known about the classification, epidemiology, tumor pathogenesis and management of patients. Additionally we present the results of our own 10-years observation after endoscopic and surgery treatment of this tumors.

Purpose: To report a patient who showed neuroendocrine tumor (carcinoid) metastasis to the medial rectus muscle and to review patients' characteristics of carcinoid metastases to the extraocular muscles., Case: A 72-year-old woman, who initially presented with spindle-shaped enlargement of the right medial rectus muscle, was followed for 3 years with a diagnosis of orbital myositis. Initial biopsy of the medial rectus muscle showed inflammation only. She showed remission and exacerbation of right proptosis and eyelid swelling, which responded to oral and intravenous steroids. On the occasion of abdominal computed tomography for ischemic colitis, a large retroperitoneal mass was detected and diagnosed as well-differentiated neuroendocrine tumor. The gradual increase of the medial rectus muscle with optic nerve compression, and hence, visual reduction, prompted a second excisional biopsy of the medial rectus mass, which proved to be neuroendocrine tumor metastasis. Whole body 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography fused with computed tomography revealed abnormal uptake only in the right orbit (maximum standardized uptake value: SUVmax = 3.83), and the patient underwent radiation to the right orbit with the subsidence of the residual mass., Results: The literature review found 15 patients, including this patient, with neuroendocrine tumor metastases to the extraocular muscles. Frequent symptoms and signs were diplopia, proptosis, and ocular motility limitation., Conclusions: Neuroendocrine tumor appears to have propensity to extraocular muscle metastases and its slow growth might pose difficulty in differential diagnoses of orbital myositis.

Carcinoid tumors with a primary site in the central nervous system have not been reported in literature yet. We report here about a 41-year-old patient with recurrent and progressive low back pain and bilateral S1 radiculopathy on admission. The patient underwent hemi-laminectomies of the vertebral bodies L5 and S1 and an en bloc resection of the tumor. Postoperative histopathological examination resulted in a well-differentiated intrathecal neuroendocrine tumor (carcinoid) of the terminal filum. Postoperative staging showed no pathological abnormalities and no tumor recurrence after 6 months. Even though rare, carcinoids should be considered as differential diagnosis of tumors occurring in the CNS.

Background: Bronchial carcinoid is an infrequent neoplasm with a neuroendocrine differentiation. Surgical treatment is the gold standard therapy, with procedures varying from sublobar resections to complex lung sparing broncoplastic procedures. This study evaluates the results of surgical treatment of bronchial carcinoids and its prognostic factors., Patients and Methods: Retrospective review of 126 consecutive patients who underwent surgical treatment for bronchial carcinoid tumors between December 1974 and July 2007., Results: There were 70 females (55%) and the mean age was 46 years, ranging from 17 to 81 years. Upon clinical presentation, 38 patients (30%) have had recurrent respiratory tract infection, 31 (24%) cough, 16 (12%) chest pain and 25 (20%) were asymptomatic. Preoperative bronchoscopic diagnosis was obtained in 74 cases (58.7%). The procedures performed were: 19 sublobar resections (14,9%), 58 lobectomies (46%), 8 bilobectomies (6.3%), 6 pneumonectomies (4.7%), 2 sleeve segmentectomies (1.5%), 26 sleeve lobectomies (20.6%) and 9 bronchoplastic procedures without lung resection (7.1%). Operative mortality was 1.5% (n = 2) and morbidity was 25.8% (n=32), including 12 respiratory tract infections and 4 reinterventions due to bleeding (3) and pleural empyema (1). Among the 112 patients available for follow-up, the overall survival at 3, 5 and 10 years was 89.2%, 85.5% and 79.8%, respectively. Five and 10-year survival for typical and atypical carcinoids were 91, 89% and 56, 47%, respectively. Overall disease-free survival at 5 years was 91.9% Statistical analysis showed that overall disease-free survival correlated with histology--typical vs. atypical--(p = 0.04) and stage (p = 0.02)., Conclusion: Surgery provides safe and adequate treatment to bronchial carcinoid tumors. Histology and stage were the main prognostic factors., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

Pulmonary neuroendocrine tumors, especially small cell carcinoma and typical carcinoids, are the most common cause of ectopic Cushing syndrome (CS). Sometimes these adrenocorticotropic hormone (ACTH)-producing tumors are too small to localize, and it may take a long time to identify them. This report describes the case of a 27-year-old-man with CS. This CS was due to the ectopic ACTH produced by the pulmonary atypical carcinoids, which were recognized at the disseminated stage 5 years after the initial presentation of CS. Microscopically, multiple whitish nodules (up to 1.0 cm in diameter) of the wedge-resected lung were composed of small round cells appearing to be typical neuroendocrine but were diagnosed as atypical carcinoid, based on the findings of focal necrosis, high mitotic rates and multiple endolymphatic tumor emboli. Immunohistochemically, tumor cells robustly stained for ACTH. The delay of diagnosis is, in part, attributable to the pulmonary tuberculosis (one of the complications of hypercortisolism), because the pulmonary tuberculosis presented in the form of multiple nodules throughout the lung. In addition, this patient had a Crooke's cell hyperplasia of the pituitary gland, which represents the reactive change of corticotrophs exposed to the excess cortisol rather than neoplastic change leading to CS.

Carcinoid tumours of the gastrointestinal tract are uncommon, generally slow-growing and associated with a good prognosis. We present a 52-year-old Chinese woman with a carcinoid at the ampulla of Vater, a site far less common than other areas of the gastrointestinal tract. Preoperative imaging showed a pancreatic mass with displacement and possible invasion of the portal vein associated with peripancreatic nodal enlargement. A radical pancreaticoduodenectomy with portal vein wedge excision was performed. An intraoperative biopsy of the enlarged nodes was negative for malignancy and postoperative histology of the large pancreatic mass yielded a surprising finding of a carcinoid tumour at the ampulla of Vater with a large inflammatory pancreatic mass adherent to the portal vein. This is an uncommon case associated with "pseudotumour pancreatitis", causing biliary and pancreatic duct obstruction mimicking a large tumour in the head of the pancreas.

Background and Aims: Well-differentiated neuro-endocrine ileal carcinoids are composed of serotonin-producing enterochromaffin (EC) cells. Life expectancy is determined by metastatic spread to the liver because medical treatment options are still very limited. Selective inhibition of angiogenesis or lymphangiogenesis might prevent tumour growth and metastatic spread. We examined the role of the vascular endothelial growth factors (VEGFs) A, B, C, D, and their receptors (VEGFRs) 1, 2, 3 in angiogenesis and lymphangiogenesis of ileal EC cell carcinoids with and without liver metastases., Methods: The expression of various VEGFs and VEGFRs was determined by quantitative real-time RT-PCR in healthy mucosa, primary tumour, lymph node metastases and liver metastases of 25 patients with ileal EC cell carcinoids. Microvessel density (MVD) was determined by CD-31 staining in primary tumours and lymphatic vessel density (LVD) by LYVE-1 staining. VEGF expression levels, MVD, LVD, and patients' survival time were correlated using logistic regression and Kaplan-Meier survival analysis., Results: VEGF-A was highly expressed with no difference between normal mucosa and tumours. VEGF-B and -D as well as VEGFR-1 and -2 expression levels were significantly increased in the tumours when compared to normal mucosa. Patients with liver metastasis, however, had a significantly lower expression of the factors A, B, and C and the receptors 2 and 3. MVD in primary tumours positively correlated with the expression of VEGF ligands and their receptors, except for VEGF-D. LVD did not correlate with any VEGF ligand or receptor. Interestingly, low expression levels of VEGF-B were associated with poor survival., Conclusion: Patients with more aggressive metastatic spreading had relatively decreased expression levels of VEGF ligands and receptors. Thus, anti-angiogenic therapy may not be a suitable target in metastatic ileal EC cell carcinoids., (Copyright 2009 S. Karger AG, Basel.)

Carcinoid tumors are neuroendocrine neoplasms, primarily of the gastrointestinal tract. Their incidence has been increasing over the last 2 to 3 decades. Patients often present with vague, nonspecific symptoms. Thus, primary care physicians should keep this diagnosis in mind and start appropriate diagnostic testing if they suspect it on a clinical basis. Patients with carcinoid tumors are also at increased risk of developing other malignancies, so close follow-up by their primary care physician is necessary.

Background: Paraneoplastic neurological syndromes (PNS) are mainly associated with small-cell lung cancer, gynaecological tumours and lymphomas. Few studies report the association of neurological syndromes with a carcinoid, the majority being a serotonin-related myopathy. We report four patients with a PNS associated with carcinoid., Patients and Results: The clinical syndromes were sensory neuropathy, limbic encephalitis, myelopathy and brain stem encephalitis. Two patients had antineuronal autoantibodies (one anti-Hu, one anti-Yo), one patient had antinuclear antibodies, and one patient had no autoantibodies. For two of the carcinoids, expression of HuD in the tumour could be demonstrated., Conclusion: This study demonstrates that carcinoids can also be associated with classical antineuronal antibody-associated PNS.

Objective: Mainstem bronchus obstruction results in lung function exclusion. The aim of this study was to revisit lung function restoration obtained by different types of bronchial sleeve resections in selected patients with endobronchial tumors., Methods: Eleven patients (9 women and 2 men, mean age 47 years) presented with endobronchial tumors and ipsilateral lung function exclusion. Mainstem bronchial sleeve resection was performed in 7 patients, right bilobar and mainstem bronchial sleeve resection in 2, and left upper sleeve lobectomy in 2. Tumors consisted in 8 bronchial carcinoids, 2 adenoid cystic carcinomas, and one inflammatory myofibroblastic tumor. Fiberoptic bronchoscopy and quantitative ventilation-perfusion lung scan were performed in all patients at work-up to assess lung function exclusion and during the first year following bronchoplastic procedure to study recovery. Long-term follow-up consisted of physical examination, thoracic computed tomographic scan and bronchoscopy every year., Results: There was no postoperative death. The long-term follow-up was complete and ranged from 12 to 192 months (median: 102.7 months). The lung function was completely restored in all patients. The ventilation function was immediate, but the perfusion was restored in a mean interval of 8.2 months (ranging from 3 to 12 months). All patients are currently alive, and no local tumor recurrence was observed., Conclusions: Some obstructing tumors may be removed by various types of bronchial sleeve resections that permit lung function restoration and long-term local control of the disease. However, at least one year is required for lung perfusion to completely recover, despite immediate ventilation restoration.

This study sought to determine the clinical profiles and optimal management of primary hepatic carcinoid tumours. The clinical features of nine Chinese patients and 64 patients reported in the English-language literature were characterized. Recurrence rate and survival analysis were performed with the Kaplan-Meier method. The impact of surgical resection and post-operative recurrence on survival was determined by means of the log-rank test. Carcinoid syndrome complicated 10 cases (14%). Sixty-two patients (85%) underwent surgical resection. Actuarial 5- and 10-year survival rates for resected patients were 80% and 75%, respectively. Twelve patients experienced recurrences: the recurrence rate at 5 years post-operatively was 26%. All patients with resectable recurrent disease achieved good long-term survival and no significant relationship was found between recurrence and survival. Owing to the high incidence of recurrence, long-term follow-up is necessary and it is recommended that recurrent cases should be managed with judicious surgical resection.

Although carcinoid tumor is a relatively common neoplasm in surgical pathology, fine needle aspiration cytology (FNAC) as a method of primary diagnosis has only been reported a few times. We report the case of a 55-year-old male patient who presented with colicky pain in the abdomen and a vague mass in the right lumbar region. Ultrasonographic study showed an enlarged mesenteric lymph node. Ultrasonography-guided FNAC revealed cellular smears with neuroendocrine cellular arrangement and morphology. The cytomorphologic characteristics of carcinoid tumors are distinctive enough for diagnosis. A diagnosis of metastatic carcinoid was given. 5-hydroxyindolacetic acid in 24-hour urine turned out to be high. Histopathology and immunohistochemistry studies also confirmed the diagnosis. Thus, FNAC can be a useful and safe tool in the diagnosis of carcinoid tumors.

Gastrointestinal carcinoid tumors arise from cells of the diffuse neuroendocrine system localized in the digestive trace and represent more than 70% of all carcinoid tumors in humans. The present article reviews the following topics: 1) The biological profile of these tumors (histopathology, cytokine markers, metabolic alterations, storage of neuroamines and hormonal proteins, cytodynamic behavior, and biological behavior according to embryological origin). 2) The etiological circumstances (exceptional hereditary factors, association of gastric carcinoid tumors with autoimmune gastritis, little-known exogenous factors). 3) Pathogenic aspects (persistent mitogenesis of endocrine cells associated with hypergastrinemia, inactivation of some putative tumor suppressor genes, the doubtful participation of oncogenes, autocrine action of some cellular growth-stimulating proteins). 4) The repercussions of certain physiopathological events (peritumoral desmoplastic reaction causing the "mass effect" on the digestive tube, the "kidnapping" of dietary tryptophan by tumoral cells toward an abnormal metabolic pathway; the easy metastatic dissemination coexisting with low tumoral aggressivity, and the release into the bloodstream of stored secretory products leading to "carcinoid syndrome" and some endocrine hyperfunction syndromes. Finally, it should be remembered that gastrointestinal carcinoid tumors represent only a proportion of the neoplasms classified as neuroendocrine tumors.

Primary tumors of the trachea are rare and can be missed because of the paucity of symptoms and findings and the difficulty in detecting them with chest radiographs. A 31-year-old male patient was admitted with complaints of shortness of breath, coughing, phlegm, and blood in the sputum. He stated that he was being treated for chronic obstructive pulmonary disease. Fiberoptic bronchoscopy revealed a vegetative mass with a wide base on the posterolateral wall of the distal one-third of the trachea. Postoperative histopathological examination revealed a typical carcinoid tumor. In patients with an unexplained cough, dyspnea, infrequent hemoptysis, and normal pulmonary imaging findings, tracheal carcinoma should be suspected. In such cases, early thoracic computed tomography and bronchoscopic examination can provide a rapid diagnosis and treatment options and prevent a false diagnosis.

In endocrine cells, plasma membrane (PM)-bound secretory granules must undergo a number of maturation stages (i.e., priming) to become fusion-competent. Despite identification of several molecules involved in binding granules to the PM and priming them, the exact nature of events occurring at the PM still largely remains a mystery. In stimulated BON cells, we used evanescent wave microscopy to study trajectories of granules shortly before their exocytoses, which provided a physical description of vesicle-PM interactions at an unprecedented level of detail, and directly lead to an original mechanistic model. In these cells, tethered (T), nonfusogenic, vesicles are prevented from converting to fusogenic, docked (D) ones in resting conditions. Upon elevation of calcium, T-vesicles perform a 21-nm step toward the PM to become D, and fuse approximately 3 s thereafter. Our ability to directly visualize different modes of PM-attachment paves the way for clarifying the exact role of various molecules implicated in attachment and priming of granules in future studies.

Carcinoid cancers arise from the neuroendocrine cell system of the gastrointestinal tract, lungs, and other organs. Hepatic metastases are common, and patients often suffer from endocrinopathies secondary to tumor secretion of various hormones and peptides. As complete surgical resection is often not possible because of widespread disease, new therapeutic and palliative treatments are needed. In this study, we characterized the effects of suberoyl bishydroxamic acid (SBHA), a histone deacetylase inhibitor, on the growth and neuroendocrine phenotype of carcinoid cancer cells. SBHA treatment of human gastrointestinal and pulmonary carcinoid cancer cells resulted in a dose-dependent inhibition of cell proliferation. Western blot analysis showed a decrease in cyclin D1 and an increase in p21 and p27, indicating that the mechanism of this growth inhibition is cell cycle arrest. Furthermore, SBHA treatment suppressed two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. These changes in the growth and neuroendocrine phenotype of carcinoid cells were associated with activation of the Notch1 signaling cascade. We conclude that SBHA shows promise as a potential anticancer agent for the treatment of patients with advanced carcinoid tumor disease.

Type 1 diabetes is usually associated with other autoimmune diseases. Parietal cell antibodies (PCA) are found in 20% of type 1 diabetic patients which might be an early sign of autoimmune gastritis and pernicious anemia. PCA destroy the gastric H+/K+ ATP-ase. The chronic auto-destruction of the proton pump leads to hypo/achlorhydria and hypergastrinemia which leads to the hyper/dysplasia of enterochromaffin-like cells (ECL). ECL hyper/dysplasia is known to increase the likelihood of gastric carcinoid tumor development in affected patients. Gastric carcinoid tumors forming from the hyperplasia of ECL cells are found in 4-9% of patients having autoimmune gastritis or pernicious anemia. The 29-years-old type 1 diabetic patient, having primer hyperthyroidism was admitted to our clinic because of gastric pain. Results of endoscopy and biopsy showed multiple small polyps in the fundus with non-antral hypergastrinemic (type A) atrophic gastritis. The parietal cell antibody test was positive, the serum chromogranin A level was 289,7 ng/ml (normal value $ 98 ng/ml), TSH level was 9,93 mIU/L. The histological examination indicated carcinoid tumor. Sandostatin therapy was started then partial gastrectomy was done. After the operation the plasma chromogranin level normalized. Non-antral, multiple polyps could cover silent neuroendocrine tumors, which are slowly growing benign endocrine tumors, however, they also might be high malignity endocrine carcinomas. These tumors could be easily recognized in the clinical practice by measuring the serum or tissue chromogranin A level and other markers of tumor growth. Thus screening of gastric endocrine tumors in type 1 diabetic patients with co-morbid autoimmune diseases is recommended.

Background: The aim was to investigate HRQoL and psychosocial function among patients with carcinoid tumours, longitudinally and prospectively, and to compare HRQoL among patients with carcinoid tumours to that of the Swedish general population. The aim was also to investigate the prevalence of distress during the first year after diagnosis., Methods: At four assessments during the first year after diagnosis, HRQoL was measured by the EORTC QLQ-C30 3.0, anxiety and depression by the HADS, and prevalence, and worst aspects of distress by an interview guide. ANOVA was performed in order to study changes over time with regard to HRQoL, anxiety and depression. Comparisons regarding HRQoL between patients and the Swedish population were made by the use of one-sample t-tests and changes over time regarding the prevalence of distress was investigated by means of Cochran's Q., Results: High levels of physical-, emotional-, cognitive-, and social function and somewhat lower levels of role function and global quality of life were reported at all assessments. Role- and emotional function increased over time. Patients reported lower role function and global quality of life and more problems with fatigue and diarrhoea than the Swedish general population, at all assessments. Fatigue, limitations to work and pursue daily activities, and worry that the illness will get worse were among the most prevalent aspects at all assessments. At all assessments the majority reported worrying about the family's situation, the ability to care for the family, and worrying before the check-up., Conclusion: It is concluded that HRQoL and psychosocial function among patients with carcinoid tumours remains stable during the first year, that the patients report a lower HRQoL than the Swedish general population, and that a majority of the patients report a number of aspects of emotional distress. In the clinical care, it should be considered that the majority of patients report not only fatigue and diarrhoea but also worries about their prognosis, their families, tests, and examinations. Efforts to reduce these worries should be made.

Carcinoid tumors of ampulla are rare clinical entities. They form 0.35% of all the gastrointestinal carcinoids. So far, only 109 cases have been reported in the literature, mostly as individual case reports. Since the metastatic potential and the tumor size have no correlation, unlike in duodenal carcinoids, pancreatoduodenectomy is considered the treatment of choice. Here we present a case of carcinoid of ampulla presenting to our department.

Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index >/=1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p/=1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p/=1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

Background: Gastric carcinoid tumours are rare, but are increasing in incidence., Aim: To discuss tumour pathogenesis and outline current approaches to patient management., Methods: Review of published articles following a Pubmed search., Results: Although interest in gastric carcinoids has increased since it was recognized that they are associated with achlorhydria, to date there is no definite evidence that humans taking long-term acid suppressing medication are at increased risk. Type I tumours are associated with autoimmune atrophic gastritis and hypergastrinaemia, type II are associated with Zollinger-Ellison syndrome, multiple endocrine neoplasia-1 and hypergastrinaemia and sporadic type III carcinoids are gastrin-independent and carry the worst prognosis. Careful investigation of these patients is required, particularly to identify the tumour type, the source of hypergastrinaemia and the presence of metastases. Treatment can be directed at the source of hypergastrinaemia if type I or II tumours are still gastrin responsive and not growing autonomously. Type III tumours should be treated surgically., Conclusions: Advances in our understanding of the pathogenesis of gastric carcinoids have led to recent improvements in investigation and management. Challenges remain in identifying the genetic and environmental factors, in addition to hypergastrinaemia, that are responsible for tumour development in susceptible patients.

Context: Carcinoid tumors are exceedingly rare in the genitourinary tract and may occur in the kidney, urinary bladder, urethra, or prostate., Objective: To review the clinical and pathologic features of carcinoid tumors occurring in the urinary tract and prostate., Data Sources: We searched the English language literature using MEDLINE and Ovid., Conclusions: Carcinoid tumors of the urinary tract and prostate share similar morphologic features with their counterparts in other organs. The differential diagnosis includes metastatic carcinoid tumor, paraganglioma, and nested variants of urothelial and prostatic carcinomas. Correlation of the clinical presentation and histopathologic features (including the immunohistochemical profile) will ensure accurate diagnosis of these rare tumors.

A 52-year-old woman presented with symptoms of virilization, which had been ongoing for 5 months. At the age of 34 years, she had a large abdominal carcinoid tumour removed. Twelve years later, she presented with Cushing's syndrome due to ectopic adrenocorticotrophic hormone (ACTH) production by carcinoid metastases localized in the right parametrium, fornix posterior and right diaphragm. Debulking laparotomy was performed followed by remission of hypercortisolism. Relapse of hypercortisolism followed 3 years later, and a second debulking laparotomy was performed including resection of the right ovary. In the following year, relapses of hypercortisolism were observed until bilateral adrenalectomy was performed. Laboratory evaluation revealed elevated serum levels of testosterone (23.0 nmol/l), androstenedione and 17-hydroxyprogesterone, and a serum estradiol (E2) level in the premenopausal range. The computerized tomography (CT) of the abdomen showed a large pelvic mass on the left side of the uterus without a recognizable left ovary. Treatment with a GnRH agonist (goserelin, 3.6 mg s.c., monthly) was initiated, resulting in normalization of the androgen levels. One year later, obstruction of the right ureter occurred due to progression of the pelvic metastases, thus a third debulking laparotomy with resection of the pelvic metastases including the left ovary was performed. The microscopic examination of the removed pelvic mass showed malignant carcinoid tissue with focal remnants of atrophic ovarian tissue. Two years after surgery, serum androgen levels are undetectable. We hypothesize that the high levels of ACTH at the site of the left ovary have induced androgen hypersecretion by steroid-producing cells in the ovary of our patient.

Carcinoid tumors are uncommon pulmonary neoplasms. They are classified histologically as either atypical or typical. Atypical carcinoids are aggressive malignancies that require radical surgical resection and have a guarded prognosis with a propensity to metastasize and recur. Typical carcinoids are low-grade malignancies with relatively less metastatic or recurring potential and are usually treated with simple excision. Recurrence of a typical pulmonary carcinoid tumor more than a decade after initial resection is very rare. A patient with recurrence of a typical carcinoid tumor 11 years after resection of the primary lesion with one involved lymph node is reported here. Late recurrences are rare in both atypical and typical varieties, but are much more common in atypical carcinoids. The patient reported here represents the fifth case of recurrence of a typical carcinoid tumor more than ten years after resection. This suggests that, after resection of a typical carcinoid neoplasm, patients should be monitored carefully, especially if lymph node metastases are present at the time of surgery.

Background: Typical carcinoid (TC) tumors are relatively infrequent. Diagnosis on the basis of sputum cytology is difficult, and there are few cases reported in the literature. Partial expectoration of endobronchial tumors is a rare event that permits their cytologic diagnosis., Case: A 71-year-old, male nonsmoker sought medical attention for a cough and expectoration of 1 month's duration. After 2 negative sputum tests, the third sample revealed large tumor fragments as a result of partial expectoration of an endobronchial, growing mass., Conclusion: The diagnosis of TC is rarely made by sputum examination as the tumor is generally covered with intact bronchial mucosa. However, in our case there was partial expectoration of the tumor. This has been reported just once before in the literature.

We present a new case of a primary carcinoid tumour of the skin. The mitotic index (4/10 HPF) warrants classification of this case as atypical. The patient was a 58-year-old woman with a 1-year history of a mass on the scalp. Literature review showed this to be only the seventh case of primary carcinoid tumour of the skin. Importantly, the evolution has been favourable in all seven tumours, with a mean follow-up of 2.5 years for the previous six cases. Although the number of cases is too small to draw definitive conclusions, information to date suggests that this type of tumour can be expected to have a benign behaviour, despite the presence in some cases of criteria suggestive of uncertainty, such as the presence of mitosis.

Background: The aim of the study was to determine the presenting clinical-radiological features and outcomes of typical pulmonary carcinoid tumors in our center., Material/methods: The medical records of 24 patients with typical pulmonary carcinoid tumor diagnosed between January 1995 and December 2003 were retrospectively reviewed. Follow-up information on patients was obtained from direct patient contact in February 2004., Results: There were 17 female and 7 male patients with a mean age of 40.3 years (range: 17-69 years). Sixteen patients (66.7%) were nonsmokers. The most frequent presenting symptom was cough, followed by hemoptysis. Twenty-three patients had an abnormal chest X-ray, showing atelectasis in seven. Bronchoscopy revealed mass lesion in all cases. In 13 cases, tumor was located in the lobar bronchi. Diagnosis of carcinoid tumor was established with bronchoscopy in 19 patients and with thoracotomy in five cases. While surgery was the treatment modality in 23 patients, one patient refused treatment. Lobectomy was performed in 15 cases and six of them were sleeve lobectomy. One patient died two days after operation due to ischemic heart disease, two were lost to follow-up, and 21 patients were still alive. Survival for the 21 patients was between 5 and 96 months. Eight patients had survival of more than five years., Conclusions: Our data suggest that typical pulmonary carcinoids are different from major lung cancer types with respect to sex, age predilection, and smoking history. Surgery is the treatment of choice for pulmonary carcinoid tumors. These patients had excellent prognosis after surgical treatment.