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Carcinoid Tumors and Syndrome

Carcinoid tumors are small, well-differentiated, slow-growing neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma (NET). Carcinoid syndrome describes the signs and symptoms associated with unregulated vasoactive hormone production by neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma. Carcinoid tumors are most commonly found in the GI and bronchopulmonary tracts. Vasoactive substances produced by NET of the GI tract do not cause carcinoid syndrome until the tumors metastasize to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy. Symptoms of carcinoid syndrome include flushing, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, and wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing. Treatment consists primarily of surgical tumor Tumor Inflammation resection and therapy with somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions analogs. Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas depends on the tumor Tumor Inflammation location, aggressiveness, and overall disease burden.

Last updated: 15 Mar, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Carcinoid tumor Tumor Inflammation is a neuroendocrine tumor Tumor Inflammation arising from enterochromaffin cells, typically in the GI and bronchopulmonary tracts.

Epidemiology

  • Rare, but rising incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency, likely due to improved detection
  • The reported annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is 4.7/100,000.
  • Black patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have a higher annual rate of incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency than whites.
  • Presents in all age groups; greater incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the elderly (50–70 years)
  • No clear gender Gender Gender Dysphoria predominance
  • Carcinoid syndrome occurs in approximately 5% of carcinoid tumors

Etiology

  • Exact cause is unknown.
  • Several risk factors have been identified:
    • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics:
      • Approximately 10% of GI carcinoids are associated with multiple endocrine neoplasia type 1 Multiple endocrine neoplasia type 1 A form of multiple endocrine neoplasia that is characterized by the combined occurrence of tumors in the parathyroid glands, the pituitary gland, and the pancreatic islets. The resulting clinical signs include hyperparathyroidism; hypercalcemia; hyperprolactinemia; Cushing disease; gastrinoma; and Zollinger-Ellison syndrome. This disease is due to loss-of-function of the MEN1 gene, a tumor suppressor gene (genes, tumor suppressor) on chromosome 11 (locus: 11q13). Multiple Endocrine Neoplasia ( MEN1 MEN1 A form of multiple endocrine neoplasia that is characterized by the combined occurrence of tumors in the parathyroid glands, the pituitary gland, and the pancreatic islets. The resulting clinical signs include hyperparathyroidism; hypercalcemia; hyperprolactinemia; cushing disease; gastrinoma; and zollinger-ellison syndrome. This disease is due to loss-of-function of the men1 gene, a tumor suppressor gene on chromosome 11 (locus: 11q13). Multiple Endocrine Neoplasia).
      • Other associations: neurofibromatosis type 1 Type 1 Spinal Muscular Atrophy, Von-Hippel-Lindau (VHL) syndrome, tuberous sclerosis complex Tuberous sclerosis complex Tuberous sclerosis or tuberous sclerosis complex (TSC) is an autosomal dominant disorder with mainly neurocutaneous symptoms. Mutation in the TSC genes causes excessive tumor-like growths in the brain, eyes, heart, kidney, and lungs. Cutaneous manifestations include hypopigmentation (i.e., ash leaf spots, confetti lesions) or excessive growth (i.e., angiofibroma, shagreen patch). Tuberous Sclerosis
    • Race:
      • GI carcinoids are more common in Blacks.
      • Lung carcinoids are more common in whites.
    • Pernicious anemia Pernicious anemia A megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor. Megaloblastic Anemia: stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy carcinoids

Mnemonic

The rule of 1/3s can be used to recall the characteristics of carcinoid tumors:

  • 1/3 of carcinoid tumors metastasize.
  • 1/3 of carcinoid tumors present with 2nd malignancy Malignancy Hemothorax.
  • 1/3 of carcinoid tumors are multiple.

Pathophysiology

Carcinoid tumors

Biological behavior:

  • Low-grade indolent tumors
  • Part of the spectrum for neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma, ranging from low- and intermediate-grade (carcinoids) to high-grade tumors (small-cell lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer)

Classification based on embryonic origin:

  • Foregut Foregut Development of the Abdominal Organs carcinoids:
    • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy:
      • Type 1 Type 1 Spinal Muscular Atrophy (70%–80%): associated with chronic atrophic gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis
      • Type 2 Type 2 Spinal Muscular Atrophy: associated with Zollinger-Ellison syndrome Zollinger-ellison syndrome A syndrome that is characterized by the triad of severe peptic ulcer, hypersecretion of gastric acid, and gastrin-producing tumors of the pancreas or other tissue (gastrinoma). This syndrome may be sporadic or be associated with multiple endocrine neoplasia type 1. Esophagitis and MEN1 MEN1 A form of multiple endocrine neoplasia that is characterized by the combined occurrence of tumors in the parathyroid glands, the pituitary gland, and the pancreatic islets. The resulting clinical signs include hyperparathyroidism; hypercalcemia; hyperprolactinemia; cushing disease; gastrinoma; and zollinger-ellison syndrome. This disease is due to loss-of-function of the men1 gene, a tumor suppressor gene on chromosome 11 (locus: 11q13). Multiple Endocrine Neoplasia
      • Type 3 Type 3 Spinal Muscular Atrophy: sporadic Sporadic Selective IgA Deficiency (most aggressive type)
    • Bronchial
  • Midgut Midgut Development of the Abdominal Organs (90% of all GI carcinoids):
  • Hindgut Hindgut Development of the Abdominal Organs:
    • Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy
    • Rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy
    • Genitourinary tract (very rare)
  • Other uncommon sites:
    • Ovary
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
    • Gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy
    • Cystic duct Cystic duct The duct that is connected to the gallbladder and allows the emptying of bile into the common bile duct. Cholecystitis
    • Thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy
    • Middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media

Carcinoid syndrome

  • Carcinoid tumors sometimes secrete several substances:
    • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy carcinoids: histamine
    • Lung/bronchial carcinoids: 
      • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS
      • Gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions
      • Adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones
      • Histamine
  • Classic carcinoid syndrome is associated with midgut Midgut Development of the Abdominal Organs tumors metastatic to liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy:
    • Associated mostly with serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS production
    • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS is produced from tryptophan and converted in the body to 5-hydroxyindoleacetic acid (HIAA).
    • Effects of serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS:
      • Vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
      • ↑ Platelet aggregation Aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Coagulation Studies
    • No symptoms appear while the tumor Tumor Inflammation confined to the gut, as serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS is metabolized by the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy.
  • Other substances contributing to clinical symptoms:
    • Histamine
    • Kallikrein Kallikrein Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein, tissue kallikrein, and prostate-specific antigen. Hereditary Angioedema (C1 Esterase Inhibitor Deficiency)
    • Tachykinins
    • Prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids

Clinical Presentation

Symptoms of primary tumor Tumor Inflammation

  • Many individuals are asymptomatic and discovered incidentally on imaging.
  • Presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor depends on location:
    • Gastric: asymptomatic, discovered on endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD)
    • Small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy:
      • Asymptomatic
      • Nonspecific abdominal pain Abdominal Pain Acute Abdomen
      • Small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy obstruction/ intussusception Intussusception Intussusception occurs when a part of the intestine (intussusceptum) telescopes into another part (intussuscipiens) of the intestine. The condition can cause obstruction and, if untreated, progress to bowel ischemia. Intussusception is most common in the pediatric population, but is occasionally encountered in adults. Intussusception
    • Appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy
      • Usually asymptomatic
      • Most commonly discovered incidentally on appendectomy Appendectomy Appendectomy is an invasive surgical procedure performed with the goal of resecting and extracting the vermiform appendix through either an open or a laparoscopic approach. The most common indication is acute appendicitis. Appendectomy
    • Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy:
      • Asymptomatic until large (> 5 cm)
      • Symptoms similar to colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer when present ( pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, bleeding, obstruction)
    • Rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy
      • Mostly asymptomatic
      • Rarely cause rectal bleeding, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, change in bowel habits

Carcinoid syndrome

  • Specific symptoms depend on substances that are produced.
  • Hindgut Hindgut Development of the Abdominal Organs tumors are mostly nonsecretory.
  • Typical carcinoid syndrome:
    • Metastatic small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy and appendiceal carcinoids
    • Symptoms:
      • Episodic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions flushing (85% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship)
      • Venous telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency (late finding)
      • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
      • Bronchospasm Bronchospasm Asthma Drugs
      • Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) valvular lesions (deposits of fibrous Fibrous Fibrocystic Change tissue)
      • Retroperitoneal Retroperitoneal Peritoneum: Anatomy fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
      • Muscle wasting Muscle Wasting Duchenne Muscular Dystrophy
      • Niacin Niacin A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties. Lipid Control Drugs deficiency (from diversion of tryptophan synthesis Synthesis Polymerase Chain Reaction (PCR) to serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS synthesis Synthesis Polymerase Chain Reaction (PCR))
  • Atypical (variant) syndromes:
    • Gastric tumors:
    • Lung/bronchial tumors:
      • Specific mediator unclear, possibly histamine
      • Severe and prolonged flushing
      • Disorientation Disorientation St. Louis Encephalitis Virus/ anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
      • Tremors
      • Periorbital Periorbital Orbital and Preseptal Cellulitis edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Lacrimation/salivation
      • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension/ tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
      • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
      • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma/ dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
      • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation
  • Carcinoid crisis:
    • Rare life-threatening form of carcinoid syndrome
    • Massive release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of bioactive compounds
    • Triggered by:
Clinical presentation of carcinoid syndrome

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor of carcinoid syndrome

Image: “Carcinoid syndrome presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor” by Mikael Häggström. License: CC0 1.0, edited by Lecturio.

Diagnosis

History

  • Chronic and severe diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Flushing
  • Family history Family History Adult Health Maintenance/presence of genetic conditions ( MEN1 MEN1 A form of multiple endocrine neoplasia that is characterized by the combined occurrence of tumors in the parathyroid glands, the pituitary gland, and the pancreatic islets. The resulting clinical signs include hyperparathyroidism; hypercalcemia; hyperprolactinemia; cushing disease; gastrinoma; and zollinger-ellison syndrome. This disease is due to loss-of-function of the men1 gene, a tumor suppressor gene on chromosome 11 (locus: 11q13). Multiple Endocrine Neoplasia, VHL syndrome, NF1 NF1 Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas. Neurofibromatosis Type 1)

Laboratory studies

  • 24-hour urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat to determine 5-HIAA:
  • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products chromogranin A Chromogranin A A type of chromogranin which was first isolated from chromaffin cells of the adrenal medulla but is also found in other tissues and in many species including human, bovine, rat, mouse, and others. It is an acidic protein with 431 to 445 amino acid residues. It contains fragments that inhibit vasoconstriction or release of hormones and neurotransmitter, while other fragments exert antimicrobial actions. Pancreatic Neuroendocrine Tumors (PanNETs) levels:
  • Blood serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS: high rate of false positives
  • Blood 5-HIAA levels:
    • Relatively new test
    • Needs to be validated

Imaging

  • CT abdomen with contrast:
    • Useful in detecting liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy metastases
    • Small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy and appendiceal carcinoids are usually small and may not be detected.
    • Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy carcinoids can be seen, but cannot be distinguished from other colonic tumors.
  • MRI: more sensitive than CT for detection of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy metastases
  • Somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors scintigraphy Scintigraphy Sjögren’s Syndrome:
    • Most carcinoids express somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors.
    • Whole-body imaging
Somatostatin receptor scintigraphy of pulmonary carcinoids

Somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors scintigraphy Scintigraphy Sjögren’s Syndrome of pulmonary carcinoids:
Most carcinoid tumors express somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. Using scintigraphy Scintigraphy Sjögren’s Syndrome, a detailed whole-body scan can be performed to identify masses.

Image: “The value of somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors imaging with In-111 octreotide Octreotide A potent, long-acting synthetic somatostatin octapeptide analog that inhibits secretion of growth hormone and is used to treat hormone-secreting tumors; diabetes mellitus; hypotension, orthostatic; hyperinsulinism; hypergastrinemia; and small bowel fistula. Antidiarrheal Drugs and/or Ga-68 DOTATATE in localizing ectopic adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones-producing tumors” by Özkan ZG, Kuyumcu S, Balköse D, Ozkan B, Aksakal N, Yılmaz E, Sanlı Y, Türkmen C, Aral F, Adalet I. License: CC BY 2.5, edited by Lecturio.

Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

  • Upper and lower endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) should be performed for metastases with unknown primary.
  • Bronchoscopy Bronchoscopy Endoscopic examination, therapy or surgery of the bronchi. Laryngomalacia and Tracheomalacia for lung/bronchial lesions (can miss peripheral tumors)

Management

Primary tumors

Surgical resection is the definitive treatment for non-metastatic tumors.

  • Small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy: resection of involved segment and mesentery Mesentery A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. Peritoneum: Anatomy
  • Appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy:
    • Simple appendectomy Appendectomy Appendectomy is an invasive surgical procedure performed with the goal of resecting and extracting the vermiform appendix through either an open or a laparoscopic approach. The most common indication is acute appendicitis. Appendectomy for tumors < 2 cm confined to the appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy
    • Right hemicolectomy:
  • Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy: partial colectomy with lymphadenectomy similar to colonic adenocarcinoma
  • Rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy
    • Endoscopic excision usually feasible for small tumors
    • Low anterior or abdominoperineal resection required for tumors > 2 cm or with invasion of muscularis propria
  • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy:
  • Lung/bronchial: surgical resection

Carcinoid syndrome and metastatic disease

Medical management of carcinoid syndrome focuses on the use of somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions analogs to inhibit serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS secretion Secretion Coagulation Studies

  • Therapy with somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions analogs:
    • About 80% of GI carcinoids express somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
    • Octreotide Octreotide A potent, long-acting synthetic somatostatin octapeptide analog that inhibits secretion of growth hormone and is used to treat hormone-secreting tumors; diabetes mellitus; hypotension, orthostatic; hyperinsulinism; hypergastrinemia; and small bowel fistula. Antidiarrheal Drugs and lanreotide:
      • Bind BIND Hyperbilirubinemia of the Newborn to somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
      • Inhibit serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology
      • Provide symptomatic relief (50%–70% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship) and inhibit proliferation of tumor Tumor Inflammation cells
  • Additional therapy for refractory symptoms:
    • Telotristat: tryptophan hydroxylase inhibitor (decreases serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS production)
    • Interferons Interferons Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons
    • Anti-diarrheal medications ( loperamide Loperamide One of the long-acting synthetic antidiarrheals; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. Antidiarrheal Drugs, diphenoxylate Diphenoxylate A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. Antidiarrheal Drugs atropine Atropine An alkaloid, originally from atropa belladonna, but found in other plants, mainly solanaceae. Hyoscyamine is the 3(s)-endo isomer of atropine. Anticholinergic Drugs)
  • Hepatic resection:
    • Can be curative for resectable liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy lesions
    • Can also serve as palliation for carcinoid syndrome
    • Performed if > 90% of tumor Tumor Inflammation can be resected/ablated
  • Hepatic transarterial embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding: for unresectable liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy-dominant disease
Ct scan multiple metastatic carcinoid lesions

Computed tomography scan showing multiple metastatic carcinoid lesions of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy before hepatic artery embolization Hepatic Artery Embolization Glucagonoma (1A) and after (significant reduction in total liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy volume and confluence of metastases (1B))

Image: “Local treatment in unresectable hepatic metastases of carcinoid tumors: Experiences with hepatic artery embolization Hepatic Artery Embolization Glucagonoma and radiofrequency ablation Radiofrequency ablation Removal of tissue using heat generated from electrodes delivering an alternating electrical current in the frequency of radio waves. Hepatocellular Carcinoma (HCC) and Liver Metastases” by Meij V, Zuetenhorst JM, van Hillegersberg R, Kröger R, Prevoo W, van Coevorden F, Taal BG. License: CC BY 2.0

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Depends on the site of tumor Tumor Inflammation, stage, histological grade, and overall tumor burden Tumor burden The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body. Tumor Lysis Syndrome
  • Midgut Midgut Development of the Abdominal Organs tumors tend to metastasize more than foregut Foregut Development of the Abdominal Organs and hindgut Hindgut Development of the Abdominal Organs tumors; however, once metastatic, the tumors tend to progress slowly.
  • Overall 5-year survival: from 41.8% ( colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy) to 78% ( rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy)
  • 5-year survival with metastatic disease:
    • Lowest for colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy: 4.1%
    • Highest for small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy: 32.4%

Differential Diagnosis

  • Gastrinoma Gastrinoma A gastrinoma is a tumor that secretes excessive levels of the hormone gastrin and is responsible for Zollinger-Ellison syndrome (ZES). Gastrinomas are frequently associated with multiple endocrine neoplasia 1 (MEN 1) and can arise from the pancreas, stomach, duodenum, jejunum, and/or even from the lymph nodes. Gastrinoma: a gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions-secreting tumor Tumor Inflammation that causes Zollinger-Ellison Syndrome Zollinger-ellison syndrome A syndrome that is characterized by the triad of severe peptic ulcer, hypersecretion of gastric acid, and gastrin-producing tumors of the pancreas or other tissue (gastrinoma). This syndrome may be sporadic or be associated with multiple endocrine neoplasia type 1. Esophagitis. Tumors can arise from the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy, duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy, jejunum Jejunum The middle portion of the small intestine, between duodenum and ileum. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Small Intestine: Anatomy, and/or even lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy and can be malignant, with metastases to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and regional lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy. Symptoms include refractory peptic ulcers and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. Diagnosis is established based on fasting gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions levels. Treatment includes surgical resection and symptomatic management.
  • VIPoma VIPoma A VIPoma is a rare neuroendocrine tumor arising primarily in the pancreas that releases large amounts of vasoactive intestinal polypeptide (VIP). This process leads to chronic watery diarrhea with concomitant hypokalemia and dehydration, as well as wheezing and flushing (known as Verner-Morrison or WDHA syndrome). VIPoma: 3rd most common neuroendocrine tumor Tumor Inflammation of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy (after insulinoma Insulinoma A benign tumor of the pancreatic beta cells. Insulinoma secretes excess insulin resulting in hypoglycemia. Pancreatic Neuroendocrine Tumors (PanNETs) and gastrinoma Gastrinoma A gastrinoma is a tumor that secretes excessive levels of the hormone gastrin and is responsible for Zollinger-Ellison syndrome (ZES). Gastrinomas are frequently associated with multiple endocrine neoplasia 1 (MEN 1) and can arise from the pancreas, stomach, duodenum, jejunum, and/or even from the lymph nodes. Gastrinoma). VIPomas are associated with MEN1 MEN1 A form of multiple endocrine neoplasia that is characterized by the combined occurrence of tumors in the parathyroid glands, the pituitary gland, and the pancreatic islets. The resulting clinical signs include hyperparathyroidism; hypercalcemia; hyperprolactinemia; cushing disease; gastrinoma; and zollinger-ellison syndrome. This disease is due to loss-of-function of the men1 gene, a tumor suppressor gene on chromosome 11 (locus: 11q13). Multiple Endocrine Neoplasia and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology large amounts of vasoactive intestinal peptide Vasoactive intestinal peptide A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling ( VIP VIP A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling), which causes chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and flushing.
  • Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease: a malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion syndrome, which is also known as gluten Gluten Prolamins in the endosperm of seeds from the triticeae tribe which includes species of wheat; barley; and rye. Celiac Disease-sensitive enteropathy Enteropathy IPEX Syndrome or nontropical sprue. Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease presents with chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery. Diagnosis is established histologically. The mainstay of management is a gluten Gluten Prolamins in the endosperm of seeds from the triticeae tribe which includes species of wheat; barley; and rye. Celiac Disease-free diet.
  • Irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome ( IBS IBS Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome): a condition affecting the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. Other terminologies include spastic bowel, nervous colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, and spastic colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy. Cellular/anatomical disruption is not observed (e.g., histological findings appear normal). Irritable bowel syndrome Irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional bowel disease characterized by chronic abdominal pain and altered bowel habits without an identifiable organic cause. The etiology and pathophysiology of this disease are not well understood, and there are many factors that may contribute. Irritable Bowel Syndrome commonly presents with alternating diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea and constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, and is often a diagnosis of exclusion.

References

  1. Strosberg, J.R. (2020). Staging, treatment, and posttreatment surveillance of nonmetastatic, well-differentiated gastrointestinal tract neuroendocrine (carcinoid) tumors. Retrieved January 22, 2021, from https://www.uptodate.com/contents/staging-treatment-and-posttreatment-surveillance-of-nonmetastatic-well-differentiated-gastrointestinal-tract-neuroendocrine-carcinoid-tumors
  2. Strosberg, J.R. (2019). Clinical features of carcinoid syndrome. Retrieved January 21, 2021, from https://www.uptodate.com/contents/clinical-features-of-carcinoid-syndrome
  3. Strosberg, J.R. (2020). Treatment of the carcinoid syndrome. Retrieved January 21, 2021, from https://www.uptodate.com/contents/treatment-of-the-carcinoid-syndrome
  4. Strosberg, J.R. (2019). Clinical characteristics of well-differentiated neuroendocrine (carcinoid) tumors arising in the gastrointestinal and genitourinary tracts. Retrieved January 21, 2021, from https://www.uptodate.com/contents/clinical-characteristics-of-well-differentiated-neuroendocrine-carcinoid-tumors-arising-in-the-gastrointestinal-and-genitourinary-tracts
  5. Tebbi, C.K. (2019). Carcinoid tumor. Retrieved January 21, 2021, from https://emedicine.medscape.com/article/986050-overview
  6. Santacroce, L. (2019). Malignant carcinoid syndrome. Retrieved January 21, 2021, from https://emedicine.medscape.com/article/282515-overview

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