240 likes | 487 Views
Joint Meeting GISMAD-AIGO-SIED-SIGE DISTURBI DELLA MOTILITA’ GI NELLE PATOLOGIE SISTEMICHE. Verona, martedì 9 Marzo 2010. Sindromi paraneoplastiche da dismotilità gastrointestinale. Rosario Cuomo AOU “Federico II” – Napoli rcuomo@unina.it. Paraneoplastic syndromes.
E N D
Joint Meeting GISMAD-AIGO-SIED-SIGE DISTURBI DELLA MOTILITA’ GI NELLE PATOLOGIE SISTEMICHE Verona, martedì 9 Marzo 2010 Sindromi paraneoplastiche da dismotilità gastrointestinale Rosario Cuomo AOU “Federico II” – Napoli rcuomo@unina.it
Paraneoplasticsyndromes • Paraneoplastic disorders are non metastatic syndromes that are not attributable to toxicity of cancer therapy, infection, or toxic/metabolic causes. • They are clinically important for several reasons: • Paraneoplastic disorders often cause severe and permanent morbidity. • The symptoms are the presenting feature of an otherwise undiagnosed tumor, and so the clinician must be able to recognize and diagnose these syndromes promptly. • The paraneoplastic syndromes are an important part of the differential diagnosis of dysfunction. • Early diagnosis of a paraneoplastic disorder maximizes the likelihood of successful tumor treatment
Paraneoplasticsyndromes • The most common cancersassociatedwithparaneoplasticsyndromes include • Lung carcinoma (most common) • Renal carcinoma • Hepatocellular carcinoma • Leukemias • Lymphomas • Breasttumors • Ovariantumors • Neuralcancers • Gastriccancers • Pancreaticcancers
Paraneoplasticsyndromes • Generalparaneoplasticsymptoms • Cutaneousparaneoplasticsyndromes • Endocrine paraneoplasticsyndromes • GI paraneoplasticsyndromes • Hematologicparaneoplasticsyndromes • Neurologicparaneoplasticsyndromes • Renalparaneoplasticsyndrome • Rheumatologicparaneoplasticsyndromes
Paraneoplastic GI dismotilitysyndromes • A small proportion of patients with occult or established neoplasms develop a gastrointestinal motility disorder, referred to as paraneoplasticdysmotility. • The diagnosis of a paraneoplasticdysmotility requires the onset of gastrointestinal dysmotility associated with the presence of a tumor and presence of specific serum antibodies Kashyap P and Farrugia G, GastroenterolClin North Am. 2008
Clinical presentation of a paraneoplasticdysmotility syndrome • Pseudoachalasia • ParaneoplasticGastroparesis • Paraneoplasticchronicintestinalpseudoobstruction • Chronicconstipation Kashyap P and Farrugia G, GastroenterolClin North Am. 2008
SCLC=small-cell lung cancer; lambert-eaton myastenic syndrome
Enteric Autoantibodies and Gut Motility Disorders • Antibodies associated with paraneoplastic and idiopathic dysmotility • Type 1 antineuronal nuclear antibody (ANNA-1) recognizenuclearproteinHu (in the neurons of the central, peripheral and enteric nervous system) • Calciumchannelantibodies(Antibodies to P/Q and N type calcium channels; less frequently found compared to ANNA-1 antibodies; may coexist with ANNA-1) • Antibodies against neuronal nicotinic acetylcholine receptors (ganglionic antibodies often determine symptoms of gastrointestinal dysmotility) • Purkinje Cell Cytoplasmic Autoantibody, type 1 (PCA1) (Gastrointestinal dysmotility in a minority of PCA-1 seropositive patients +/- cerebellar ataxia in association with gynecological or breast carcinoma Kashyap P and Farrugia G, GastroenterolClin North Am. 2008
Antineuronal antibodies of the Hu type in a 55-year-old patient with paraneoplastic syndrome characterized by CIPO related to an occult small-cell lung carcinoma GASTROENTEROLOGY 2004;126:1872–1883
A 68-yr-old man developed anorexia, early satiety, nausea, and constipation and lost approximately 20 lb in 3 months. He subsequently developed daily nausea and vomiting with dysgeusia and increasedanorexia. Am J Gastroenterol 2002
Normalhumanjejunaltissue Patient’s jejunalbiopsy MP-ICC = c-Kit positive interstizialcellofCajal in mientericplexus CM = circularmuscle; LM = longitudinalmuscle Am J Gastroenterol 2002
Metastatic small-cell lung carcinoma cells in the biopsied mediastinallymphnode Hematoxylin-eosinstain Immunoreactivity of the Kit protein Am J Gastroenterol 2002
SummaryofPatientsStudied Am J Gastroenterol 2001;96:373–379
Results of Manometric and Radiographic Images in PatientsWith SCLC Results of Serological Tests for Neuronal Autoantibodies Am J Gastroenterol 2001;96:373–379
Upright plain film of the abdomen demonstrating sitz markers throughout the colon 1 month after sitz marker ingestion Supine film of the abdomen taken 1 year after the film shown in Fig 1. Extensive distention of the colon with stool is noted. Nineteen stiz markers ingested a year previously are retained. A gastrostomy tube is present. 63-year-old woman NeurogastroenterolMotil (2005) 17, 16–22
Lymphoplasmacytic infiltrate is noted in the location of the myenteric plexus. NeurogastroenterolMotil (2005) 17, 16–22
Pathogenesis of Malignant Gastroparesis in Various Cancer Types J SupportOncol 2007;5:355–363
Medical Management of Gastroparesis J SupportOncol 2007;5:355–363
Enteral tubes for the management of malignant gastroparesis J SupportOncol 2007;5:355–363
Management algorithm for paraneoplasticdysmotility • Insufficient evidence to recommend a paraneoplastic antibody profile on every patient with new onset of a gut motility disorder • The presenceofsignificantweight loss, a rapid onset of the disease, a past or present smoking history should prompt to consider testing for the presence of autoantibodies • ANNA-1 positivity: start with a CT chest and if negative follow up with a PET scan and directed biopsies of any suspicious lymph nodes or massesifindicated (SCLC 13%) • The presence of other autoantibodies without concomitant ANNA-1 positivity is less likely to predict the presence of a malignancy Kashyap P and Farrugia G, GastroenterolClin North Am. 2008
Treatment ofparaneoplasticdysmotility • No treatments have been convincingly shown to alter outcome (steroids, cyclophosphamide, plasmapheresis, immunoglobulin) • Treatment of the underlying primary malignancy • Nutritional support either enterally or parenterally • Prokinetics, treatment of bacterialovergrowth • One additional management strategy is to use high dose IV steroids for 3 days and if there is a clinical response switch to 6-mercatopurine or azathioprine (difficult in the case of chemotherapy) Kashyap P and Farrugia G, GastroenterolClin North Am. 2008