Carcinoid syndrome caused by a pulmonary carcinoid mimics intestinal manifestations of ulcerative colitis:A case report

BACKGROUND Pulmonary carcinoids are rare,low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior.Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi.Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5%of patients with neuroendocrine tumors.Due to such nonspecific presentation,most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed.CASE SUMMARY We report the case of a 48-year-old male who presented with cough,dyspnea,a history of recurrent pneumonitis,and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid.CONCLUSION We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

Direct costs of carcinoid syndrome diarrhea among adults in the United States

BACKGROUND The burden of carcinoid syndrome(CS)among patients with neuroendocrine tumors is substantial and has been shown to result in increased healthcare resource use and costs.The incremental burden of CS diarrhea(CSD)is less well understood,particularly among working age adults who make up a large proportion of the population of patients with CS.AIM To estimate the direct medical costs of CSD to a self-insured employer in the United States.METHODS CS patients with and without CSD were identified in the IBM®MarketScan®Database,including the Medicare Supplemental Coordination of Benefits database.Eligible patients had≥1 medical claim for CS with continuous health plan enrollment for≥12 mo prior to their first CS diagnosis and for≥30 d after,no claims for acromegaly,and no clinical trial participation during the study period(2014-2016).Baseline demographic and clinical characteristics,including comorbidities and treatment,were analyzed using descriptive statistics.Measures of healthcare resource use and costs were compared between patients with and without CSD,including Emergency Department(ED)visits,hospital admissions and length of stay,physician office visits,outpatient services,and prescription claims,using univariate and multivariate analyses to evaluate associations of CSD with healthcare resource use and costs,controlling for baseline characteristics.RESULTS Overall,6855 patients with CS were identified of which 4,043 were eligible for the analysis(1352 with CSD,2691 with CS only).Baseline demographic and clinical characteristics were similar between groups with the exception of age,underlying tumor type,and health insurance plan.Patients with CSD were older,had more comorbidities,and received more somatostatin analog therapy at baseline.Patients with CSD required greater use of healthcare resources and incurred higher costs than their peers without CSD,including hospitalizations(44%vs 25%)and ED visits(55%vs 31%).The total adjusted annual healthcare costs per patient were 50%higher(+$23865)among those with CSD,driven by outpatient services(+56%),prescriptions(+48%),ED visits(+26%),physician office visits(+21%),and hospital admissions(+11%).CONCLUSION The economic burden of CSD is greater than that of CS alone among insured working age adults in the United States,which may benefit from timely diagnosis and management.

Predictive factors associated with carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors

AIM To discover unknown factors associated with carcinoid syndrome(CS) with the goal of earlier diagnosis of CS.METHODS In this retrospective case-control study using United States administrative claims, patients(≥ 18 years) newly-diagnosed with gastrointestinal neuroendocrine tumors(GI NETs) without CS(controls) were exactly matched to patients with CS(cases) based on NET diagnosis date at a 3-to-1 ratio. Study index date was first CS diagnosis(controls: same distance from NET diagnosis as cases). The most observed conditions, excluding CS-associated symptoms/diagnoses, during the year before index date were assessed. Forwardstepwise logistic regression models were used to derive predictors, and were validation within another claims database. RESULTS In the development database, 1004 patients with GI NETs were identified; 251(25%) had CS and 753(75%) were controls. In the validation database, 724 patients with GI NETs were identified; 181(25%) had CS and 543(75%) were controls. A total of 33 common diagnoses(excluding conditions already known to be associated with CS) in the development database were entered in forward step-wise logistic regression models. In the final, validated logistic regression model, three factors prior to CS diagnosis were found consistently associated with higher risks for CS, including liver disorder [odds ratio(95%CI): 3.38(2.07-5.51)], enlargement of lymph nodes [2.13(1.10-4.11)], and abdominal mass [3.79(1.87-7.69)].CONCLUSION GI NET patients with CS were 2-4 times as likely to have preexisting diagnoses(i.e., liver disorder, enlarged lymph nodes, abdominal mass) than non-CS patients.

Managing end-stage carcinoid heart disease:A case report and literature review

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of life.Cardiovascular complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic disease.CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases.During the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to follow-up.After 10 years,he presented to the emergency room with signs and symptoms of right-sided heart failure.Panneuroendocrine markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic metastases.Computed tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis.Furthermore,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart disease.The patient was not a candidate for valve replacement.He started octreotide acetate treatment,and the dose escalated to 80 mg IM monthly.Although biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart failure.Carcinoid heart disease and tumor burden are major prognostic factors of poor survival.Therefore,they must be actively sought by available biochemical markers and imaging techniques.Moreover,imaging techniques aiding tumor detection and staging,somatostatin receptor positron emission tomography/CT,and CT or magnetic resonance imaging,should be performed at the time of diagnosis and in 3-to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery.Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered,while any delay can worsen right-sided ventricular failure.

Gastrointestinal neuroendocrine tumors in 2020

Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological,biological,and clinical characteristics that have increased in incidence and prevalence within the last few decades.They contain chromogranin A,synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor.Ki-67 index and mitotic index correlate with cellular proliferation.Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors.Most of the gastrointestinal neuroendocrine tumors are non-functional.World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm.Gastric neuroendocrine tumors arise from enterochromaffin like cells.They are classified into 4 types.Only type I and type II are gastrin dependent.Small intestinal neuroendocrine tumor is the most common small bowel malignancy.More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve.Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs.Duodenal and jejunoileal neuroendocrine tumors are distinct biologically and clinically.Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver.Appendiceal neuroendocrine tumors are generally detected after appendectomy.Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis.Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000.Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy,endoscopic ultrasound,serology of biomarkers,imaging studies and functional somatostatin scans.Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.

Flushing as atypical initial presentation of functional gallbladder neuroendocrine carcinoma: A case report

BACKGROUND Neuroendocrine neoplasms are rarely located in the gallbladder(GB),and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms.CASE SUMMARY We report a case of GB neuroendocrine carcinoma(GB-NEC)in a 65-year-old man,who presented with flushing for 2 mo.Pathological specimens of the flushed skin revealed that mucin was deposited between the collagen bundles in the dermis.Computed tomography and magnetic resonance imaging indicated neoplasm in the GB with liver invasion and enlarged lymph nodes in the portacaval space.High fluorodeoxyglucose uptake was detected in lymph nodes in the portacaval space,but distant metastasis was not seen by positron emission tomography.Ultrasound-guided needle biopsy of the GB neoplasm was suggestive of high-grade NEC.Because of the functional characteristics of poorly differentiated NEC,en bloc cholecystectomy,resection of hepatic segments IVb and V,pancreaticoduodenectomy,and regional lymphadenectomy were performed.A diagnosis of poorly differentiated NEC was made by pathological findings and immunohistochemical staining data.Ki-67 index was>80%.The patient refused adjuvant therapy and passed away in the 7th month.CONCLUSION Distinctive manifestation combined with imaging helps make correct preoperative diagnosis.Radical surgery and adjuvant chemotherapy might improve prognosis.

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.

RADIOTHERAPY OF ECTOPIC ACTH SYNDROME DUE TO THORACIC CARCINOIDS

From 1984 to 1990, six patients with histologically and endocrinologically proven ectopic ACTH syndrome were treated in our department. The lesion in five patients was clinically evident, but in the other was occult. All lesions were located within the chest. Four were thvmic carcinoid and the other two were bronchial carcinoids. Most of the patients had typical clinical manifestations of Cushing’s syndrome. Laboratory tests including histopathological examination confirmed the diagnosis of ectopic ACTH syndrome. The treatment consisted of surgical removal of the mass supplemented by radiotherapy. The results showed that after treatment all patients had satisfactory remission. Two bronchial carcinoid patients have been living for 40 and 88 months respectively without recurrence. Among 4 thymic carcinoid patients, only one has been living with no tumor for 34 months. One patient had recurrence and the other 2 died 32 and 50 months after the treatment respectively. However, the symptoms of two thymic carci

慢性难治性腹泻的原因分析

A 36-year-old male who carried a diagnosis of irritable bowel syndrome presented with chronic watery diarrhea and was found to have hepatomegaly on physical exam.A computed tomography(CT)scan of the abdomen revealed hepatomegaly with lesions suspicious for metastatic disease.A colonoscopy revealed a polypoid lesion in the terminal ileum,which was biopsied,revealing a neuroendocrine tumor(NET).He was treated with palliative octreotide and chemoembolization of liver metastases until disease progression.The case highlights the importance of considering functional NETs,especially carcinoid syndrome,in patients with chronic unresolving diarrhea,since early diagnosis allows for further treatment options that can prolong survival.