In children over the age of four who have been toilet trained, a similar condition is generally termed encopresis (or soiling), which refers to the voluntary or involuntary loss of (usually soft or semi-liquid) stool. [ 35 ]  The term pseudoincontinence is used when there is FI in children who have anatomical defects (e.g. enlarged  sigmoid colon  or anal  stenosis ). [ 2 ]  Encopresis is a term that is usually applied when there are no such anatomical defects present. The  ICD-10  classifies nonorganic encopresis under "behavioural and emotional disorders with onset usually occurring in childhood and adolescence" and organic causes of encopresis along with FI. [ 36 ]  FI can also be classified according to gender, since the cause in females may be different from males, for example it may develop following radical  prostatectomy  in males, [ 37 ]  whereas females may develop FI as an immediate or delayed consequence of damage whilst giving birth.  Pelvic anatomy  is also different according to gender, with a wider  pelvic outlet  in females. [ citation needed ]


Several severity scales exist. The  Cleveland Clinic  (Wexner) fecal incontinence score takes into account five parameters that are scored on a scale from zero (absent) to four (daily) frequency of incontinence to gas, liquid, solid, of need to wear pad, and of lifestyle changes. [ 1 ]  The Park's incontinence score uses four categories:


The fecal incontinence severity index is based on four types of leakage (gas, mucus, liquid stool, solid stool) and five frequencies (once to three times per month, once per week, twice per week, once per day, twice or more per day). Other severity scales include AMS, Pescatori, Williams score, Kirwan, Miller score, Saint Mark's score, and the Vaizey scale. [ 2 ]


FI may present with signs similar to rectal discharge (e.g. fistulae, proctitis, or rectal prolapse), pseudoincontinence, encopresis (with no organic cause), and irritable bowel syndrome. [ 2 ]


FI is generally treatable with conservative management, surgery, or both. [ 2 ]  The success of treatment depends upon the exact causes and how easily these are corrected. [ 8 ]  Treatment choice depends on the cause and severity of the disease, and the motivation and general health of the person affected. Commonly, conservative measures are used together, and if appropriate surgery is carried out. Treatments may be attempted until symptoms are satisfactorily controlled. A treatment algorithm based upon the cause has been proposed, including conservative, non-operative and surgical measures (neosphincter refers to either  dynamic graciloplasty  or artificial bowel sphincter, lavage refers to retrograde rectal irrigation). [ 2 ]


Conservative measures include dietary modification, drug treatment, retrograde anal irrigation, biofeedback retraining anal sphincter exercises. Incontinence products refer to devices such as  anal plugs  and  perineal pads  and garments such as  diapers/nappies . Perineal pads are efficient and acceptable for only minor incontinence. [ 2 ]  If all other measures are ineffective  removing the entire colon  may be an option. [ citation needed ]


Dietary modification may be important for successful management. [ 5 ]  Both diarrhea and constipation can contribute to different cases, so dietary advice must be tailored to address the underlying cause or it may be ineffective or counterproductive. In persons with disease aggravated by diarrhea or those with rectal loading by soft stools, the following suggestions may be beneficial: increase  dietary fiber ; reduce  wholegrain   cereals / bread ; reduce fruit and vegetables which contain natural laxative compounds ( rhubarb ,  figs ,  prunes / plums ); limit  beans ,  pulses ,  cabbage  and  sprouts ; reduce  spices  (especially   chili ); reduce  artificial sweeteners  (e.g. sugar-free  chewing gum ); reduce  alcohol  (especially  stout ,  beer  and  ale ); reduce  lactose  if there is some degree of  lactase deficiency ; and reduce  caffeine . Caffeine lowers the resting tone of the anal canal and also causes diarrhea. Excessive doses of  vitamin C ,  magnesium ,  phosphorus  and/or  calcium  supplements may increase FI. Reducing the olestra fat substitute, which can cause diarrhea, may also help. [ 39 ]


Pharmacological management may include anti-diarrheal/constipating agents and laxatives/stool bulking agents. Stopping or substituting any previous medication that causes diarrhea may be helpful in some (see  table ). There is no good evidence for the use of any medications, however. [ 40 ]


In people who have undergone  gallbladder removal , the  bile acid sequestrant   cholestyramine  may help minor degrees of FI. [ 41 ]  Bulking agents also absorb water, so may be helpful for those with diarrhea. A common side effect is  bloating  and  flatulence .  Topical agents  to treat and prevent dermatitis may also be used, such as topical  antifungals  when there is evidence of perianal  candidiasis  or occasionally mild topical anti-inflammatory medication. Prevention of secondary lesions is carried out by perineal cleansing,  moisturization , and the use of a skin protectant. [ 42 ]


Evacuation aids ( suppositories  or  enemas ) e.g.  glycerine  or  bisacodyl  suppositories may be prescribed. People may have a poor resting tone of the anal canal, and consequently may not be able to retain an enema, in which case  transanal irrigation  (retrograde anal irrigation) may be a better option, as this equipment utilizes an inflatable catheter to prevent loss of the irrigation tip and to provide a water tight seal during irrigation. A volume of lukewarm water is gently pumped into the colon via the anus. People can be taught how to perform this treatment in their own homes, but it does require special equipment. If the irrigation is efficient, the stool will not reach the rectum again for up to 48 hours. [ 43 ]  By regularly emptying the bowel using transanal irrigation, controlled bowel function is often re-established to a high degree in patients with bowel incontinence and/or constipation. This enables control over the time and place of evacuation and the development of a consistent bowel routine. [ 43 ]  However, persistent leaking of residual irrigation fluid during the day may occur and make this option unhelpful, particularly in persons with obstructed defecation syndrome who may have an incomplete evacuation of any rectal contents. Consequently, the best time to carry out the irrigation is typically in the evening, allowing any residual liquid to be passed the next morning before leaving the home. Complications such as  electrolyte imbalance  and  perforation  are rare. The effect of transanal irrigation varies considerably. Some individuals experience complete control of incontinence, and others report little or no benefit. [ 43 ]  It has been suggested that if appropriate, people be offered home retrograde anal irrigation. [ 8 ]


Biofeedback  (the use of equipment to record or amplify and then feed back activities of the body) is a commonly used and researched treatment, but the benefits are uncertain. [ 44 ]  Biofeedback therapy varies in the way it is delivered, but it is unknown if one type has benefits over another. [ 44 ]


The role of  pelvic floor exercises  and anal sphincter exercises in FI is poorly determined. While there may be some benefits they appear less useful than implanted sacral nerve stimulators. These exercises aim to increase the strength of the pelvic floor muscles (mainly levator ani). The anal sphincters are not technically part of the pelvic floor muscle group, but the EAS is a voluntary, striated muscle that therefore can be strengthened in a similar manner. It has not been established whether pelvic floor exercises can be distinguished from anal sphincter exercises in practice by the people doing them. This kind of exercise is more commonly used to treat urinary incontinence, for which there is a sound evidence base for effectiveness. More rarely are they used in FI. The effect of anal sphincter exercises are variously stated as an increase in the strength, speed, or endurance of voluntary contraction (EAS). [ 44 ]


Electrical stimulation can also be applied to the anal sphincters and pelvic floor muscles, inducing muscle contraction without traditional exercises (similar to  transcutaneous electrical nerve stimulation , TENS). The evidence supporting its use is limited, and any benefit is tentative. [ 45 ]  In light of the above, intra-anal electrical stimulation (using an anal probe as an electrode) appears to be more efficacious than intra-vaginal (using a vaginal probe as an electrode). [ 45 ]  Rarely, skin reactions may occur where the electrodes are placed, but these issues typically resolve when the stimulation is stopped. Surgically implanted  sacral nerve stimulation  may be more effective than exercises, and electrical stimulation and biofeedback may be more effective than exercises or electrical stimulation by themselves. [ 44 ]  TENS is also sometimes used to treat FI by  transcutaneous tibial nerve stimulation . [ 46 ]


In a minority of people, anal plugs may be useful for either standalone therapy or in concert with other treatments. [ 47 ]  Anal plugs (sometimes termed tampons) aim to block the involuntary loss of fecal material, and they vary in design and composition. [ 8 ]   Polyurethane  plugs were reported to perform better than those made of polyvinyl-alcohol. [ 47 ]  Plugs are less likely to help those with frequent bowel movements, [ 2 ]  and many find them difficult to tolerate. [ 47 ]


In women, a device that functions as an inflatable balloon in the vagina has been approved for use in the United States. [ 48 ]


Surgery may be carried out if conservative measures alone are not sufficient to control incontinence. There are many surgical options, and their relative effectiveness is debated due to a lack of good-quality evidence. The optimal treatment regime may be both surgical and non-surgical treatments. [ 49 ]  The surgical options can be considered in four categories: restoration and improvement of residual sphincter function (sphincteroplasty, sacral nerve stimulation, tibial nerve stimulation, correction of anorectal deformity), replacement/imitation of the sphincter or its function (anal encirclement,  SECCA procedure , non-dynamic graciloplasty,  perianal injectable bulking agents  and  implantable bulking agents ), dynamic sphincter replacement (artificial bowel sphincter, dynamic graciloplasty), antegrade continence enema ( Malone procedure ), and finally fecal diversion (e.g. colostomy). [ 1 ]  A surgical treatment algorithm has been proposed. Isolated sphincter defects (IAS/EAS) may be initially treated with sphincteroplasty and if this fails, the person can be assessed for sacral nerve stimulation. Functional deficits of the EAS and/or IAS (i.e. where there is no structural defect, or only limited EAS structural defect, or with neurogenic incontinence) may be assessed for sacral nerve stimulation. If this fails, neosphincter with either dynamic graciloplasty or artificial anal sphincter may be indicated. Substantial muscular and/or neural defects may be treated with neosphincter initially. [ 10 ]


FI is thought to be very common, [ 1 ]  but much under-reported due to embarrassment. One study reported a prevalence of 2.2% in the general population. [ 2 ]  It affects people of all ages but is more common in older adults (but it should not be considered a normal part of aging). [ 50 ]  Females are more likely to develop it than males (63% of those with FI over 30 may be female). [ 1 ]  In 2014, the  National Center for Health Statistics  reported that one out of every six seniors in the U.S. who lived in their own homes or apartment had FI. Men and women were equally affected. [ 51 ]  45–50% of people with FI have severe physical and/or mental disabilities. [ 1 ]  People with dementia are four times more likely to have fecal incontinence compared to people of similar ages. [ 52 ] [ 53 ]


Risk factors include age, female gender, urinary incontinence, history of vaginal delivery (non- Caesarean section  childbirth), obesity, [ 32 ]  prior anorectal surgery, poor general health, and physical limitations. Combined urinary and fecal incontinence is sometimes termed double incontinence, and it is more likely to be present in those with urinary incontinence. [ 54 ]


Traditionally, FI was thought to be an insignificant complication of surgery, but it is now known that a variety of different procedures are associated with this possible complication, and sometimes at high levels. Examples are midline internal sphincterotomy (8% risk), lateral internal sphincterotomy,  fistulectomy , fistulotomy (18–52%), hemorrhoidectomy (33%),  ileo-anal reservoir reconstruction , lower anterior resection, total abdominal colectomy,  ureterosigmoidostomy , [ 32 ]  and  anal dilation  (Lord's procedure, 0-50%). [ 55 ]  Some authors consider obstetric trauma to be the most common cause. [ 56 ]


While the first mention of urinary incontinence occurs in 1500 BC in the  Ebers Papyrus , the first mention of FI in a medical context is unknown. [ 57 ]  For many centuries, colonic irrigation was the only treatment available. Stoma creation was described in AD 1776, FI associated with rectal prolapse in AD 1873 and anterior sphincter repair in AD 1875. During the mid 20th century, several operations were developed for instances where the sphincters were intact but weakened. [ 58 ]  Muscle transpositions using the  gluteus maximus  or the gracilis were devised, but did not become used widely until later. End-to-end sphincteroplasty is shown to have a high failure rate in 1940. In AD 1971, Parks and McPartlin first describe an overlapping sphincteroplasty procedure. Biofeedback is first introduced in 1974. [ 59 ]  In 1975, Parks describes post anal repair, a technique to reinforce the pelvic floor and EAS to treat idiopathic cases. Endoanal ultrasound is invented in 1991, which starts to demonstrate the high number of occult sphincter tears following vaginal deliveries. In 1994, the use of an endoanal coil during pelvic MRI shows greater detail of the anal canal than previously. During the last 20 years, dynamic graciliplasty, sacral nerve stimulation, injectable perianal bulking agents and radiofrequency ablation have been devised, mainly due to the relatively poor success rates and high morbidity associated with the earlier procedures. [ 58 ]


Persons with this symptom are frequently ridiculed and ostracized in public. It has been described as one of the most psychologically and socially debilitating conditions in an otherwise healthy individual. In older people, it is one of the most common reasons for admission into a care home. Persons who develop FI earlier in life are less likely to marry and obtain employment. Often, people will go to great lengths to keep their condition secret. It has been termed "the silent affliction" since many do not discuss the problem with their close family, employers, or clinicians. They may be subject to gossip, hostility, and other forms of social exclusion. [ 60 ] [ 61 ] [ 62 ]  The economic cost has not received much attention.


In the Netherlands, a 2004 study estimated that total costs of patients with fecal incontinence were €2169 per patient per year. Over half of this was productivity loss in work. [ 63 ]


In the US, the average lifetime cost (treatment and follow-up) was $17,166 per person in 1996. The average hospital charge for sphincteroplasty was $8555 per procedure. Overall, in the US, the total charges associated with surgery increased from $34 million in 1998 to $57.5 million in 2003.  Sacral nerve  stimulation, dynamic  graciloplasty , and  colostomy  were all shown to be cost-effective. [ 64 ]


Some insults in Japan relate to incontinence, such as  kusotare/kusottare  and  shikkotare  which mean  shit hanger/leaker/oozer  and  piss leaker/oozer  respectively, though these have not been in common use since the 1980s. [ 65 ]


The case  Hiltibran et al v. Levy et al  in the  United States District Court for the Western District of Missouri  resulted in that court issuing an order in 2011. That order requires  incontinence briefs  funded by  Medicaid  to be given by the State of Missouri to adults who would be institutionalized without them. [ 66 ] [ 67 ] [ 68 ]


Engineered  anal sphincters grown from  stem cells  have been successfully implanted in mice. New blood vessels developed and the tissue displayed normal contraction and relaxation. In the future, these methods may become part of the management of FI, replacing the need for high-morbidity implanted devices such as the artificial bowel sphincter. [ 69 ]


Fibrosing colonopathy  is a disease that arises in people with  cystic fibrosis  treated with high doses of  pancreatic enzyme supplements . [ 1 ] [ 2 ]  Symptoms are non-specific with  abdominal pain ,  abdominal swelling ,  vomiting , and  constipation . [ 1 ]


Risk factors include being young, prior surgery of the intestines, and the use of certain medications including  corticosteroids  and  H2 blockers . [ 2 ]  It may appear similar to  distal intestinal obstruction syndrome  or  inflammatory colitis  such as  Crohn's disease . [ 1 ]


A maximum dose of 10,000 IU of  lipase  per kilogram per day is recommended for  pancreatic enzyme supplementation  to prevent this condition. [ 3 ]  More than 60 cases have been described as of 1999. [ 2 ]  The disease was suggested to be caused by  methacrylic acid copolymer  which is used as coating for delayed release of enzymes but there is no reliable evidence for that. [ 4 ]


Clinical symptoms of fibrosing colonopathy can be similar to those of  intestinal obstruction  and include  constipation  or  diarrhea ,  abdominal pain ,  hematochezia , [ 5 ]   vomiting ,  nausea , and poor weight gain. [ 6 ]


The precise etiopathogenesis is still unknown. Young age (2–13 years), gastrointestinal history (DIOS,  meconium ileus ), abdominal surgery in the past,  HDPE , and use of  histamine H2-receptor blockers ,  corticosteroids , or recombinant human  deoxyribonuclease  (DNase) are risk factors. [ 7 ]  Fibrosing colonopathy and  cystic fibrosis  have a strong correlation. [ 6 ]


The afflicted colon's histologic findings include thickening of the  muscularis propria , submucosal fibrosis, a cobblestone-like appearance, and persistent mucosal inflammation. [ 8 ]  With relative rectal sparing, imaging can demonstrate diffuse narrowing, shortening, and loss of haustration of the colonic lumen. [ 9 ]


One of the most common locations for a  foreign body  is the  alimentary tract . It is possible for foreign bodies to enter the tract either from the  mouth , [ 1 ]  or from the  rectum . [ 2 ]


The objects most commonly swallowed by children are  coins . [ 3 ]  Meat impaction, resulting in  esophageal food bolus obstruction  is more common in adults. [ 4 ]  Swallowed objects are more likely to lodge in the  esophagus  or  stomach  than in the  pharynx  or  duodenum . [ 5 ]


If the person who swallowed the foreign body is doing well, usually an  x-ray  image will be taken which will show any metal objects, and this will be repeated a few days later to confirm that the object has passed all the way through the digestive system. Also it needs to be confirmed that the object is not stuck in the airways, in the bronchial tree. [ citation needed ]


Most objects that are swallowed will, if they have passed the  pharynx , pass all the way through the  gastrointestinal tract  unaided. [ 6 ]  However, sometimes an object becomes arrested (usually in the terminal  ileum  or the  rectum ) or a sharp object penetrates the  bowel  wall. If the foreign body causes problems like pain, vomiting or bleeding it must be removed. [ citation needed ]


Swallowed  batteries  can be associated with additional damage, [ 7 ] [ 8 ]  with  mercury poisoning  (from  mercury batteries ) and  lead poisoning  (from  lead batteries ) presenting important risks. [ citation needed ]


While swallowed coins typically traverse the alimentary tract without further incident, care must be taken to monitor patients, as reaction of the metals in the coin with gastric acid and other digestive juices may produce various toxic compounds if the coin remains within the alimentary tract for a prolonged period of time. [ 9 ]


Endoscopic foreign body retrieval  is the first-line treatment for removal of a foreign body from the alimentary tract. [ 10 ]


Glucagon  has been used to treat esophageal foreign bodies, with the intent that it relaxes the smooth muscle of the lower esophageal spincter to allow the foreign body to pass into the stomach. [ 10 ]  However, evidence does not support a benefit of treatment with glucagon, and its use may result in side effects. [ 11 ]


In 2018, an international team of six  paediatric  health-care professionals undertook a self-administered test, by swallowing a  Lego  piece (specifically, a  Lego minifigure   head ) and checking when the pieces appeared. They developed a Stool Hardness and Transit (SHAT) score to normalise stool consistency over time, and resulted in a Found and Retrieved Time (FART) score.  The principal finding of this study, the FART score (n = 5), ranged from 1.14 days (27 h 20 min) to 3.04 days (72 h 35 min), with an average retrieval time of 1.71 days. Their conclusion: "This international, multicentre trial identified that small objects, such as those swallowed by children, are likely to pass in 1–3 days without complication. This should offer reassurance for parents." [ 12 ]


Functional gastrointestinal disorders  ( FGID ), also known as  disorders of gut–brain interaction , include a number of separate  idiopathic  disorders which affect different parts of the  gastrointestinal tract  and involve  visceral hypersensitivity  and  motility  disturbances. [ 1 ]


Using the Delphi method, the  Rome Foundation  and its board of directors, chairs and co-chairs of the  ROME IV  committees developed the current definition for disorders of gut-brain interaction. [ 2 ]


A group of disorders classified by GI symptoms related to any combination of: [ 2 ]


Terms such as  functional colonic disease  (or  functional bowel disorder ) refer in medicine to a group of  bowel  disorders which are characterized by chronic abdominal complaints without a structural or biochemical cause that could explain symptoms. Other  functional  disorders relate to other aspects of the process of  digestion . [ 1 ]


The consensus review process of meetings and publications organised by the Rome Foundation, known as the  Rome process , has helped to define the functional gastrointestinal disorders. [ 3 ]  Successively, the Rome I, Rome II, Rome III and Rome IV proposed consensual classification system and terminology, as recommended by the Rome Coordinating Committee. These now include classifications appropriate for adults, children and neonates/toddlers. [ 1 ]


The current  ROME IV classification , published in 2016, is as follows: [ 1 ]


A. Esophageal disorders


B. Gastroduodenal disorders


C. Bowel disorders


D. Centrally mediated disorders of gastrointestinal pain


E. Gallbladder and sphincter of Oddi disorders


F. Anorectal disorders


G. Childhood functional GI disorders: Neonate/Toddler


H. Childhood functional GI disorders: Child/Adolescent


FGIDs share in common any of several physiological features including increased motor reactivity, enhanced visceral hypersensitivity, altered mucosal immune and inflammatory function (associated with bacterial  dysbiosis ), and altered central nervous system and  enteric nervous system  (CNS-ENS) regulation.


The pathophysiology of FGID has been best conceptualized using  biopsychosocial model  help to explain the relationships between an individual factors in their early life that in turn can influence their psychosocial factor and physiological functioning. This model also shows the complex interactions between these factors through the  brain-gut axis . [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]  These factors affect how FGID manifest in terms of symptoms but also affect the clinical outcome. These factors are interconnected and the influences on these factors are bidirectional and mutually interactive.


Early life factors include genetic factors, psychophysiological and sociocultural factors, and environmental exposures.


There is a strong link between FGIDs and psychosocial factors. Psychosocial factors influence the functioning of the GI tract through the brain-gut axis, including the GI tract's motility, sensitivity, and barrier function. Psychosocial factors also affect experience and behavior, treatment selection, and clinical outcome.


Psychological stress or one's emotional response to stress exacerbates gastrointestinal symptoms and may contribute to FGID development and maintenance. [ 2 ] [ 13 ]  Specifically in children and adolescents, anxiety and depression may present as FGID-associated somatic complaints, such as  nausea ,  vomiting , and  abdominal pain . [ 14 ]  Similarly,  anxiety  in individuals with FGIDs is linked to greater pain severity, frequency, duration, chronicity, and disabling effects. [ 15 ]  This is because psychological stress can impact the gut's mucosal barrier functions, allowing bacteria and bacterial products to migrate and cause pain, diarrhea, and other GI symptoms. Conversely, since the  brain-gut axis  is bidirectional, GI inflammation and injury can amplify pain signals to the brain and contribute to worsened mental status, including  anxiety  and  depression  symptoms. [ 1 ]


Individuals with FGIDs may also experience poor socialization. Due to the nature of the disease, individuals with an FGID may have difficulty with regular school or work attendance and participation in extracurricular activities, leading to isolation and a lack of peer support. This lack of peer support may lead to depression and loneliness, conditions which exacerbate FGIDs symptoms. [ 16 ]  In addition, children with FGIDs are more likely to experience bullying. As such, stressful situations which influence socialization (seen as either a lack thereof or negative experiences) may lead to an impaired functioning in patients with FGIDs. [ 17 ]


Family interactions may also play a role in the development of FGIDs through their effects on the physical and psychosocial functioning of an individual. Family factors which may influence the development of an FGID include child attachment style, maladaptive parenting behaviors (paternal rejection and hostility), and even the parents' health status, as children of chronically ill parents experience increased  somatization , insecure attachment, and worsened biopsychosocial functioning. [ 18 ]  Each of these factors leads to the accumulation of stressors, which can ultimately lead to the development of an FGID. In addition, family units which have a member with an FGIDs diagnosis are more likely to face family functioning difficulties, including challenges to familial roles, communication, affective involvement, organization, and cohesion. These challenges arise due to the nature of the disease, and ultimately worsen symptoms for the FGID patient. [ 18 ] [ 19 ]


The physiology of FGID is characterized by abnormal motility, visceral hypersensitivity as well as dysregulation of the  immune system  and barrier function of the GI tract as well as inflammatory changes.


The brain-gut axis is a bidirectional mechanism in which psychosocial factors influence the GI tract and vice versa. Specifically, the emotional and cognitive centers of the brain influence GI activity and immune cell function, and the microbes within the gut regulate mood, cognition, and mental health. [ 29 ]  These two systems interact through several mechanisms. There are direct, physical connections between the central nervous system and nerve plexuses to the visceral muscles. In addition, neurotransmitters send signals related to thoughts, feelings, and pain regulation from the brain to the GI tract. The brain-gut axis influences the entire body through a variety of pathways; it regulates sensory, motor, endocrine, autonomic, immune, and inflammatory reactions. Within the physical and psychological interactions of FGIDs specifically, psychiatric disorders such as anxiety, depression, and even autism are well-linked to GI dysfunction. Conversely, functional GI diseases are linked to several comorbid psychiatric diseases. [ 29 ]  Negative emotions such as fear, anxiety, anger, stress, and pain may delay gastric emptying, decrease intestinal and colonic transit time, and induce defecation and diarrhea. [ 1 ]


Because FGIDs are known to be multifactorial with external stressors and environmental factors playing a role in their development, current research demonstrates that psychological treatments may be effective in relieving some symptoms of the disease. Interventions such as cognitive behavioral therapy (CBT), hypnotherapy, and biofeedback-assisted relaxation training (BART) each show promise in symptom reduction. [ 30 ]  Each of these therapies aims to alter an individual's thought patterns and behaviors while improving self-efficacy, which all work together to improve health outcomes.


Cognitive behavioral therapy is a treatment based on the theory that thinking affects one's feelings and behaviors. As such, alterations in one's thought process can have a positive or negative effect on actions and perceptions. Through the lens of FGIDs, a negative thought pattern may be associated with a negative physical experience of abdominal pain, discomfort, and general sickness. In theory, retraining the patient's thought patterns can alleviate these symptoms and improve quality of life. In patients with FGIDs, CBT is an effective treatment option; one study found 87.5% of participants to be completely pain-free following treatment. [ 16 ]  Internet-based CBT (iCBT) is similarly effective, and may be a good treatment option for individuals who either cannot afford or otherwise lack access to traditional CBT. [ 31 ]


Hypnotherapy, another method for reducing symptoms of FGIDs, teaches users how to alter their perception of uncomfortable sensations in the body. Gut-directed hypnotherapy specifically gives greater improvements in symptoms than standard treatment of the disease. [ 18 ]  Research demonstrates directed hypnotherapy to be an effective mechanism of reducing visceral hypersensitivity (a low pain threshold of the internal organs) and sympathetic activity, due to the reduced activity of the anterior cingulated cortex and state of relaxation achieved during hypnosis. [ 32 ]  For patients with irritable bowel syndrome (IBS) and functional abdominal pain (FAP), hypnotherapy reduces pain intensity and frequency. [ 30 ]


BART therapies monitor the physiological changes occurring with thoughts, feelings, and emotions. These therapies aim to teach patients how to visualize the effects of the interventions they are undergoing. BART is used to improve mood and somatic responses to anxiety disorders, which may relieve some of the psychological and physiological symptoms of FGIDs. [ 33 ]  The visual, real-time feedback given through BART empowers the patient to see the difference that the therapy is making, thus giving the patient control over the physiological components of the disease. This allows the patient to maximize their mind-body connection and eventually optimize symptom management and quality of life. BART allows the patient to break the positive feedback loop of anxiety and pain, thus reducing disease exacerbations.


Antidepressants have been thoroughly studied as a potential treatment for FGIDs. Tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and selective norepinephrine reuptake inhibitors (SNRIs) show the most promise in treating some of the symptoms of FGIDs. TCAs, specifically amitriptyline, show promising results when examining common FGIDs symptoms such as pain and poor quality of life. [ 34 ]  SNRIs also demonstrate pain-relieving qualities. [ 30 ]  SSRIs are less effective in pain management, but may reduce symptoms of anxiety and depression, which would, in turn, reduce some FGIDs symptoms. [ 1 ]


Functional gastrointestinal disorders are very common. Globally, irritable bowel syndrome and functional dyspepsia alone may affect 16–26% of the population. [ 1 ] [ 35 ]


There is considerable research into the causes, diagnosis and treatments for FGIDs. Diet, microbiome, genetics, neuromuscular function and immunological response all interact. [ 1 ]  A role for mast cell activation has been proposed as one of the factors. [ 36 ] [ 37 ]


A  fundic gland polyp  is a type of  polyp , found in the  fundus  of the  stomach . Fundic gland polyps are found in 0.8 to 1.9% of patients who undergo  esophagogastroduodenoscopy , and are more common in middle-aged women. [ 2 ]


The risk of malignancy is very low or none, when sporadic. [ 3 ]


Fundic gland polyposis  is a medical syndrome with multiple fundic gland polyps. The condition has been described both in patients with  familial adenomatous polyposis  (FAP) and attenuated variants (AFAP), and in patients in whom it occurs sporadically. [ 4 ]


Fundic gland polyposis  is a medical syndrome where the  fundus  and the  body  of the  stomach  develop many  fundic gland polyps . The condition has been described both in patients with  familial adenomatous polyposis  (FAP) and attenuated variants (AFAP), and in patients in whom it occurs sporadically. [ 1 ]


Most patients with fundic gland polyps (FGPs) do not have any symptoms, and the diagnosis is made on  gastroscopy  done for other reasons.  Retrospective analysis of patients with sporadic FGPs shows that a high percentage do have symptoms, but that this is more likely to be related to the underlying disease responsible for the polyposis. [ 2 ]   These symptoms include:


The polyps on endoscopy are usually tiny, numerous and  sessile , [ 3 ]  and usually scattered throughout the fundus of the stomach, where  parietal cells  are more numerous.  They have the same colour as the gastric mucosa, and never have a stalk. [ 4 ]
When the polyps are  biopsied , the pathology typically shows shortened  gastric pits , and both superficial and deep cystic lesions in the fundic glands, lined by all three types of cells of acid-producing mucosa: mucous,  parietal and chief cells. As sometimes parietal cell hyperplasia may develop deep dilations of gland, [ 5 ]  one should be really strict in the diagnosis of FGPs (i.e. the presence of deep and superficial dilations). Infrequently, the two lesions may coexist. [ 3 ]   Foci of dysplasia can sometimes be seen. [ 4 ]


FGPs can be found in association with the following genetic conditions: [ 4 ]


Sporadic FGPs [ 1 ]  have been associated with:


The development of polyps depends on the underlying disorder. [ 17 ]  In sporadic cases of FGPs, more than 90% of patients have activating mutations in the β-catenin gene, so that they may be considered "neoplastic" polyps. [ 18 ]


In familial adenomatous polyposis, the abnormality is a mutation in the APC gene, resulting in its inactivity.  Attenuated FAP can occur from other mutations in the APC gene, and causes a  phenotype  wherein  colonic  polyps may be few in number. [ 4 ]


Both the β-catenin gene and the APC gene are involved in the same cell growth signalling pathway, but the APC gene is known to have a significantly higher association with the development of colorectal tumors. [ 19 ]


The most important consideration in evaluating patients with FGPs is distinguishing between sporadic form (patients without any other gastrointestinal condition, usually in middle age with female prevalence) and syndromic form.  This is to ascertain the risk of development of  gastric cancer  and to ascertain the risk of concomitant  colon cancer . [ 20 ] [ 21 ]


There is a risk of development of cancer with fundic gland polyposis, [ 22 ]  but it varies based on the underlying cause of the polyposis. [ 4 ]   The risk is highest with congenital polyposis syndromes, and is lowest in acquired causes. [ 4 ] [ 23 ]   As a result, it is recommended that patients with multiple fundic polyps have a  colonoscopy  to evaluate the colon. [ 4 ]  If there are polyps seen on colonoscopy,  genetic testing  and testing of family members is recommended. [ 4 ]
In the gastric adenocarcinoma associated with proximal polyposis of the stomach (GAPPS), there is a high risk of early development of proximal gastric adenocarcinoma. [ 9 ] [ 10 ]


It is still unclear which patients would benefit with surveillance  gastroscopy , but most physicians recommend endoscopy every one to three years to survey polyps for dysplasia or cancer. [ 4 ]   In the event of high grade dysplasia, polypectomy, which is done through the endoscopy, or partial  gastrectomy  may be recommended.  One study showed the benefit of  NSAID  therapy in regression of gastric polyps, but the efficacy of this strategy (given the side effects of NSAIDs) is still dubious. [ 24 ]


Gallstone ileus  is a rare form of  small bowel obstruction  caused by an impaction of a  gallstone  within the  lumen  of the  small intestine . Such a gallstone enters the bowel via a  cholecysto - enteric   fistula . The presence of large stones, >2.5 cm in diameter, within the gallbladder are thought to predispose to fistula formation by gradual erosion through the  gallbladder  fundus. [ 1 ]  Once a fistula has formed, a stone may travel from the gallbladder into the bowel and become lodged almost anywhere along the  gastrointestinal tract .  Obstruction occurs most commonly at the near the distal  ileum , within 60 cm proximally to the ileocecal valve. [ 2 ] [ 3 ]  Rarely, gallstone ileus may recur if the underlying fistula is not treated. [ 4 ]


First described by  Thomas Bartholin  in 1654, the name "gallstone ileus" is a misnomer because an  ileus  is, by definition, a  non-mechanical  bowel motility failure  (as opposed to a mechanical obstruction by a stone).


Diagnosis of gallstone ileus requires radiographic studies.  Classic radiographic findings are known as  Rigler's triad : [ 5 ]


Initial management involves fluid resuscitation and potentially nasogastric suctioning. [ 1 ]  Since gallstone ileus constitutes a form of mechanical small bowel obstruction, it can be a surgical emergency and requires open or laparoscopic surgery to remove an impacted stone. [ 1 ]  The different strategies for surgical management are either enterolithotomy alone, allowing a delayed  cholecystectomy  after an inflammation-free period of 4–6 weeks (and therefore two-stage surgery) or enterolithotomy in combination with a  cholecystectomy  and  fistula  division (one-stage surgery). The different strategies for surgical management are controversial, and depend on factors such as patient fitness for surgery and comorbidities. [ 4 ]


Bouveret's syndrome  refers to reverse gallstone ileus where the gallstone propagates proximally and causes gastric outlet obstruction by being impacted in first part of duodenum.


Gastrointestinal bleeding  ( GI bleed ), also called  gastrointestinal hemorrhage  ( GIB ), is all forms of  bleeding  in the  gastrointestinal tract , from the  mouth  to the  rectum . [ 9 ]  When there is significant  blood  loss over a short time, symptoms may include  vomiting red blood ,  vomiting black blood ,  bloody stool , or  black stool . [ 1 ]  Small amounts of bleeding over a long time may cause  iron-deficiency anemia  resulting in  feeling tired  or  heart-related chest pain . [ 1 ]  Other symptoms may include  abdominal pain ,  shortness of breath ,  pale skin , or  passing out . [ 1 ] [ 9 ]  Sometimes in those with small amounts of bleeding no symptoms may be present. [ 1 ]


Bleeding is typically divided into two main types:  upper gastrointestinal bleeding  and  lower gastrointestinal bleeding . [ 2 ]  Causes of upper GI bleeds include:  peptic ulcer  disease,  esophageal varices  due to liver  cirrhosis  and  cancer , among others. [ 3 ]   Causes of lower GI bleeds include:  hemorrhoids , cancer, and  inflammatory bowel disease  among others. [ 2 ] [ 1 ]  Small amounts of bleeding may be detected by  fecal occult blood  test. [ 1 ]   Endoscopy  of the lower and upper gastrointestinal tract may locate the area of bleeding. [ 1 ]   Medical imaging  may be useful in cases that are not clear. [ 1 ]  Bleeding may also be diagnosed and treated during  minimally invasive   angiography  procedures such as  hemorrhoidal artery embolization . [ 10 ] [ 11 ]


Initial treatment focuses on  resuscitation  which may include  intravenous fluids  and  blood transfusions . [ 4 ]  Often blood transfusions are not recommended unless the  hemoglobin  is less than 70 or 80 g/L. [ 7 ] [ 12 ]  Treatment with  proton pump inhibitors ,  octreotide , and  antibiotics  may be considered in certain cases. [ 5 ] [ 6 ] [ 13 ]  If other measures are not effective, an  esophageal balloon  may be attempted in those with presumed esophageal varices. [ 2 ]   Endoscopy of the esophagus, stomach, and duodenum  or  endoscopy of the large bowel  are generally recommended within 24 hours and may allow treatment as well as diagnosis. [ 4 ]


An upper GI bleed is more common than lower GI bleed. [ 2 ]  An upper GI bleed occurs in 50 to 150 per 100,000 adults per year. [ 8 ]  A lower GI bleed is estimated to occur in 20 to 30 per 100,000 per year. [ 2 ]  It results in about 300,000 hospital admissions a year in the  United States . [ 1 ]  Risk of death from a GI bleed is between 5% and 30%. [ 1 ] [ 7 ]  Risk of bleeding is more common in males and increases with age. [ 2 ]


Gastrointestinal bleeding can be roughly divided into two clinical syndromes:  upper gastrointestinal bleeding  and  lower gastrointestinal bleeding . [ 2 ]  About 2/3 of all GI bleeds are from upper sources and 1/3 from lower sources. [ 14 ]  Common causes of gastrointestinal bleeding include  infections ,  cancers , vascular disorders, adverse effects of medications, and  blood clotting disorders . [ 2 ]  Obscure gastrointestinal bleeding (OGIB) is when a source is unclear following investigation. [ 15 ]


Upper gastrointestinal bleeding is from a source between the  pharynx  and the  ligament of Treitz . An upper source is characterised by  hematemesis  (vomiting up blood) and  melena  (tarry stool containing altered blood). About half of cases are due to  peptic ulcer disease  ( gastric  or  duodenal ulcers ). [ 3 ]   Esophageal inflammation  and erosive disease are the next most common causes. [ 3 ]  In those with  liver cirrhosis , 50–60% of bleeding is due to  esophageal varices . [ 3 ]  Approximately half of those with peptic ulcers have an  H. pylori  infection. [ 3 ]  Other causes include  Mallory-Weiss tears , cancer, and  angiodysplasia . [ 2 ]


A number of medications are found to cause upper GI bleeds. [ 16 ]   NSAIDs  or  COX-2 inhibitors  increase the risk about fourfold. [ 16 ]   SSRIs ,  corticosteroids , and  anticoagulants  may also increase the risk. [ 16 ]  The risk with  dabigatran  is 30% greater than that with  warfarin . [ 17 ]


Lower gastrointestinal bleeding is typically from the colon, rectum or anus. [ 2 ]  Common causes of lower gastrointestinal bleeding include  hemorrhoids , cancer, angiodysplasia,  ulcerative colitis ,  Crohn's disease , and  aortoenteric fistula . [ 2 ]  It may be indicated by the passage of  fresh red blood rectally , especially in the absence of  bloody vomiting . Lower gastrointestinal bleeding could also lead to melena if the bleeding occurs in the small intestine or proximal colon. [ 1 ]


Gastrointestinal bleeding can range from small non-visible amounts, which are only detected by laboratory testing, to massive bleeding where bright red blood is passed and  shock  develops. Rapid bleeding may cause  syncope . [ 18 ]  The presence of bright red blood in stool, known as  hematochezia , typically indicates lower gastrointestinal bleeding. Digested blood from the upper gastrointestinal tract may appear black rather than red, resulting in "coffee ground" vomit or melena. [ 2 ]  Other signs and symptoms include  feeling tired ,  dizziness , and pale skin color. [ 18 ]


A number of foods and medications can turn the stool either red or black in the absence of bleeding. [ 2 ]   Bismuth  found in many antacids may turn stools black as may  activated charcoal . [ 2 ]  Blood from the vagina or urinary tract may also be confused with blood in the stool. [ 2 ]


Diagnosis is often based on direct observation of blood in the stool or vomit.  Although  fecal occult blood  testing has been used in an emergency setting, this use is not recommended as the test has only been validated for colon cancer screening. [ 19 ]  Differentiating between upper and lower bleeding in some cases can be difficult. The severity of an upper GI bleed can be judged based on the  Blatchford score [ 4 ]  or  Rockall score . [ 16 ]  The Rockall score is the more accurate of the two. [ 16 ]  As of 2008 there is no scoring system useful for lower GI bleeds. [ 16 ]


Gastric aspiration and or lavage , where a tube is inserted into the stomach via the nose in an attempt to determine if there is blood in the stomach, if negative does not rule out an upper GI bleed [ 20 ]  but if positive is useful for ruling one in. [ 14 ]  Clots in the stool indicate a lower GI source while melana stools an upper one. [ 14 ]


Recommended laboratory blood testing includes: cross-matching blood, hemoglobin, hematocrit, platelets, coagulation time, and electrolytes. [ 4 ]  If the ratio of  blood urea nitrogen  to  creatinine  is greater than 30 the source is more likely from the upper GI tract. [ 14 ]


A  CT angiography  is useful for determining the exact location of the bleeding within the gastrointestinal tract. [ 21 ]  Nuclear scintigraphy is a sensitive test for detecting occult gastrointestinal bleeding when direct imaging with upper and lower endoscopies are negative. Direct angiography allows for embolization of a bleeding source, but requires a bleeding rate faster than 1mL/minute. [ 22 ]


In patients with significant varices or cirrhosis  nonselective β-blockers  reduce the risk of future bleeding. [ 13 ]  With a target heart rate of 55 beats per minute B-blockers reduce the absolute risk of bleeding by 10%. [ 13 ]   Endoscopic band ligation  (EBL) is also effective at improving outcomes. [ 13 ]  Either B-blockers or EBL is recommended as initial preventative measures. [ 13 ]  In patients who have had a previous variceal bleed both treatments are recommended. [ 13 ]  Some evidence supports the addition of  isosorbide mononitrate . [ 23 ]  Testing for and treating those who are positive for  H. pylori  is recommended. [ 16 ]   Transjugular intrahepatic portosystemic shunting  (TIPS) may be used to prevent bleeding in people who re-bleed despite other measures. [ 16 ]


Among patients admitted to the ICU with high risk of bleeding, a PPI or H2RA appears useful. [ 24 ] [ 25 ]


The initial focus is on  resuscitation  beginning with airway management and fluid resuscitation using either intravenous fluids and or blood. [ 4 ]  A number of medications may improve outcomes depending on the source of the bleeding. [ 4 ]


Based on evidence from people with other health problems  crystalloid  and  colloids  are believed to be equivalent for peptic ulcer bleeding. [ 4 ]   Proton pump inhibitor  (PPI) treatment before endoscopy may decrease the need for endoscopic hemostatic treatment, however it is not clear if this treatment reduces mortality, the risk of re-bleeding, or the  [ clarification needed ]  and the need for surgery. [ 26 ]  Oral and intravenous formulations may be equivalent; however, the evidence to support this is suboptimal. [ 27 ]  In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance. [ 26 ]  There is tentative evidence of benefit for  tranexamic acid  which inhibits clot breakdown. [ 28 ]   Somatostatin  and  octreotide , while recommended for varicial bleeding, have not been found to be of general use for non variceal bleeds. [ 4 ]  After treatment of a high risk bleeding ulcer endoscopically giving a PPI once or a day rather than as an infusion appears to work just as well and is less expensive (the method may be either by mouth or intravenously). [ 29 ]


For initial fluid replacement, colloids or  albumin  is preferred in people with cirrhosis. [ 4 ]  Medications typically include  octreotide  or, if not available,  vasopressin  and  nitroglycerin  to reduce portal venous pressures. [ 13 ]   Terlipressin  appears to be more effective than octreotide, but it is not available in many areas of the world. [ 16 ] [ 30 ]  It is the only medication that has been shown to reduce mortality in acute variceal bleeding. [ 30 ]  This is in addition to  endoscopic banding  or  sclerotherapy  for the varices. [ 13 ]  If this is sufficient then  beta blockers  and  nitrates  may be used for the prevention of re-bleeding. [ 13 ]  If bleeding continues, balloon tamponade with a  Sengstaken-Blakemore tube  or  Minnesota tube  may be used in an attempt to mechanically compress the varices. [ 13 ]  This may then be followed by a  transjugular intrahepatic portosystemic shunt . [ 13 ]  In those with cirrhosis,  antibiotics  decrease the chance of bleeding again, shorten the length of time spent in hospital, and decrease mortality. [ 5 ]  Octreotide reduces the need for blood transfusions [ 31 ]  and may decrease mortality. [ 32 ]  No trials of  vitamin K  have been conducted. [ 33 ]


The evidence for benefit of blood transfusions in GI bleed is poor with some evidence finding harm. [ 8 ]  In those in  shock   O-negative packed red blood cells  are recommended. [ 2 ]  If large amounts of pack red blood cells are used additional  platelets  and  fresh frozen plasma  (FFP) should be administered to prevent  coagulopathies . [ 4 ]  In  alcoholics  FFP is suggested before confirmation of a coagulopathy due to presumed blood clotting problems. [ 2 ]  Evidence supports holding off on blood transfusions in those who have a  hemoglobin  greater than 7 to 8 g/dL and moderate bleeding, including in those with preexisting  coronary artery disease . [ 7 ] [ 12 ]


If the INR is greater than 1.5 to 1.8 correction with fresh frozen plasma or  prothrombin complex  may decrease mortality. [ 4 ]  Evidence of a harm or benefit of  recombinant activated factor VII  in those with liver diseases and gastrointestinal bleeding is not determined. [ 34 ]  A  massive transfusion protocol  may be used, but there is a lack of evidence for this indication. [ 16 ]


The benefits versus risks of placing a  nasogastric tube  in those with upper GI bleeding are not determined. [ 4 ]  Endoscopic evaluation within 24 hours is recommended, [ 4 ]  in addition to medical management. [ 35 ]  A number of endoscopic treatments may be used, including:  epinephrine  injection, band ligation, sclerotherapy, and fibrin glue depending on what is found. [ 2 ]  Prokinetic agents such as  erythromycin  before endoscopy can decrease the amount of blood in the stomach and thus improve the operators view. [ 4 ]  They also decrease the amount of blood transfusions required. [ 36 ]  Early endoscopy decreases hospital and the amount of blood transfusions needed. [ 4 ]  A second endoscopy within a day is routinely recommended by some [ 16 ]  but by others only in specific situations. [ 22 ]  Proton pump inhibitors, if they have not been started earlier, are recommended in those in whom high risk signs for bleeding are found. [ 4 ]  High and low dose PPIs appear equivalent at this point. [ 37 ]  It is also recommended that people with high risk signs are kept in hospital for at least 72 hours. [ 4 ]  Those at low risk of re-bleeding may begin eating typically 24 hours following endoscopy. [ 4 ]  If other measures fail or are not available,  esophageal balloon tamponade  may be attempted. [ 2 ]  While there is a success rate up to 90%, there are some potentially significant complications including  aspiration  and  esophageal perforation . [ 2 ]


Colonoscopy  is useful for the diagnosis and treatment of lower GI bleeding. [ 2 ]  A number of techniques may be employed including clipping, cauterizing, and sclerotherapy. [ 2 ]  Preparation for colonoscopy takes a minimum of six hours which in those bleeding briskly may limit its applicability. [ 38 ]  Surgery, while rarely used to treat upper GI bleeds, is still commonly used to manage lower GI bleeds by cutting out the part of the intestines that is causing the problem. [ 2 ]   Angiographic embolization  may be used for both upper and lower GI bleeds. [ 2 ]   Transjugular intrahepatic portosystemic shunting  (TIPS) may also be considered. [ 16 ]


Death in those with a GI bleed is more commonly due to other illnesses (some of which may have contributed to the bleed, such as cancer or cirrhosis) than the bleeding itself. [ 2 ]  Of those admitted to a hospital because of a GI bleed, death occurs in about 7%. [ 16 ]  Despite treatment, re-bleeding occurs in about 7–16% of those with upper GI bleeding. [ 3 ]  In those with esophageal varices, bleeding occurs in about 5–15% a year and if they have bled once, there is a higher risk of further bleeding within six weeks. [ 13 ]  Testing and treating  H. pylori  if found can prevent re-bleeding in those with peptic ulcers. [ 4 ]  The benefits versus risks of restarting blood thinners such as  aspirin  or  warfarin  and  anti-inflammatories  such as  NSAIDs  need to be carefully considered. [ 4 ]  If aspirin is needed for cardiovascular disease prevention, it is reasonable to restart it within seven days in combination with a PPI for those with nonvariceal upper GI bleeding. [ 22 ]


Gastrointestinal bleeding from the upper tract occurs in 50 to 150 per 100,000 adults per year. [ 8 ]  It is more common than lower gastrointestinal bleeding which is estimated to occur at the rate of 20 to 30 per 100,000 per year. [ 2 ]  Risk of bleeding is more common in males and increases with age. [ 2 ]


A  gastrojejunocolic fistula  is a disorder of the human  gastrointestinal tract . It may form between the transverse colon and the upper  jejunum  after a  Billroth II  surgical procedure.  (The Billroth procedure attaches the jejunum to the remainder of the stomach.) Fecal matter thereby passes improperly from the colon to the stomach, and causes  halitosis . [ citation needed ]


Patients may present with  diarrhea , [ 1 ]   weight loss  and  halitosis  as a result of fecal matter passing through the  fistula  from the colon into the stomach.


Globus pharyngis ,  globus hystericus  or  globus sensation  is the persistent but painless sensation of having a pill, food  bolus , or some other sort of obstruction in the  throat  when there is none. Swallowing is typically performed normally, so it is not a true case of  dysphagia , but it can become quite irritating. It is common, with 22–45% of people experiencing it at least once in their lifetime. [ 1 ] [ 2 ]


The "lump in the throat" sensation that characterizes globus pharyngis is often caused by  inflammation  of one or more parts of the throat, such as the  larynx  or  hypopharynx , due to  cricopharyngeal spasm ,  gastroesophageal reflux  (GERD), or  laryngopharyngeal reflux .
In some cases the cause is unknown and symptoms may be attributed to a  psychogenic  cause  i.e.  a  somatoform  or  anxiety disorder . It has been recognised as a symptom of depression, which responds to anti-depressive treatment. [ 3 ] [ 4 ]


The results of recent studies have strongly suggested that  GERD  is a major cause of globus, though this remains under considerable debate. [ 5 ]


A less common cause, distinguished by a "lump in the throat" accompanied with clicking sensation and considerable pain when swallowing, may be due to thyroid-cartilage rubbing against anomalous asymmetrical laryngeal anatomy  e.g.  the superior cornu abrading against the  thyroid lamina , [ 6 ] [ 7 ]  surgically trimming the offending thyroid-cartilage provides immediate relief in all cases. [ 8 ]  However this cause is frequently misdiagnosed, despite requiring a simple clinical examination involving careful palpation of the neck side to side which elicits the same click sensation (laryngeal crepitus) and pain as when swallowing, most cases are due to prior trauma to the neck. [ 8 ]  High resolution  computed tomographic  (CT) or  MRI  scan of the larynx is usually required to fully understand the anomalous laryngeal anatomy. Anterior displacement of the thyroid ala on the affected side while swallowing can help resolve symptoms. [ citation needed ]  Other anomalous laryngeal anatomy with the potential to cause the globus sensation include thyroid nodules or parathyroid adenomas. [ 9 ]


As  globus sensation  is a symptom, a diagnosis of  globus pharyngis  is typically a  diagnosis of exclusion . If globus sensation is presenting with other symptoms such as pain, swallowing disorders such as aspiration or regurgitation (dysphagia), weight loss, or voice change, [ 10 ]  an organic cause needs to be investigated, typically with  endoscopy .  Barium swallows  are not recommended as a diagnostic tool as although they are less invasive than endoscopy and may be reassuring to the patient, they commonly miss sinister causes. It is very rare that globus sensation presenting with no other symptoms has a sinister cause and therefore endoscopy is not recommended in this case. [ 10 ] [ 11 ]


Differential diagnosis must be made from  Eagle syndrome  which uses the patient's description of "something caught in my throat" as a diagnostic tool. Eagle syndrome is an elongation of the styloid process causing irritation to nerves and muscles in the region resulting in a number of unusual symptoms. [ citation needed ]


Reassurance of the patient is recommendable when no cause can be found.
If a cause is identified, treat the cause symptomatically or, if possible, systemically. [ citation needed ]


Hematochezia  is a form of  blood in stool , in which fresh  blood  passes through the  anus  while  defecating . It differs from  melena , which commonly refers to blood in stool originating from  upper gastrointestinal bleeding  (UGIB). [ 1 ]  The term derives from Greek αἷμα ("blood") and χέζειν ("to defaecate"). Hematochezia is commonly associated with  lower gastrointestinal bleeding , but may also occur from a brisk upper gastrointestinal bleed. The difference between hematochezia and  rectorrhagia  is that rectal bleeding is not associated with defecation; instead, it is associated with expulsion of fresh bright red blood without stools. [ 2 ]  The phrase  bright red blood per rectum  is associated with hematochezia and rectorrhagia.


In adults, most common causes are  hemorrhoids  and  diverticulosis , both of which are relatively benign; however, it can also be caused by  colorectal cancer , which is potentially fatal. In a newborn infant, haematochezia may be the result of swallowed maternal blood at the time of delivery, but can also be an initial symptom of  necrotizing enterocolitis , a serious condition affecting premature infants. In babies, hematochezia in conjunction with abdominal pain is associated with  intussusception . In  adolescents  and young adults,  inflammatory bowel disease , particularly  ulcerative colitis , is a serious cause of hematochezia that must be considered and excluded.


Hematochezia can be due to  upper gastrointestinal bleeding .  However, as the blood from such a bleed is usually chemically modified by action of  acid  and  enzymes , it presents more commonly as black "tarry" feces known as  melena . Haematochezia from an upper gastrointestinal source is an ominous sign, as it suggests a very significant bleed which is more likely to be life-threatening. Eating  beetroot  can cause harmless red-colored feces ( beeturia ) because of insufficient metabolism of a red pigment, and is a differential sign that may be mistaken as hematochezia. Consumption of dragon fruit ( pitaya ) or blackberries may also cause red or black discoloration of the stool and sometimes the urine (pseudohematuria). This too, is a differential sign that is sometimes mistaken for hematochezia. [ citation needed ]


In infants, the  Apt test  can be used to distinguish  fetal hemoglobin  from maternal blood.


Other common causes of blood in the stool include:


A complete blood count as well as an hemoglobin test should be performed when a patient presents symptoms of hematochezia. A colonoscopy may be necessary if there is suspicion of bleed from colon particularly in the elderly to look for the site and many causes of bleed like carcinoma, ulcerative colitis, rectal varices or other lesions and in certain instances upper gastrointestinal endoscopy may be required as well to look for any rapid and massive fresh bleed from upper gastrointestinal tract when there may not be sufficient time for the change of colour of blood to occur. [ 20 ]


High-altitude flatus expulsion  ( HAFE ) is a  gastrointestinal  syndrome which involves the spontaneous passage of increased quantities of  rectal gases  at high altitudes. [ 1 ]


High-altitude flatus expulsion was first described by Joseph Hamel in c. 1820 [ 2 ]  and occasionally described afterward. [ 3 ]  A landmark study of this phenomenon was published in 1981 by  Paul Auerbach  and York Miller. [ 1 ]


The feeling of fullness or need to expel brought on by this differential in  atmospheric pressure  has been verified by studies involving  military pilots  subjected to pressure changes simulating flight. [ 4 ]


This  human digestive system  article is a  stub . You can help Wikipedia by  expanding it .


Hirschsprung's disease  ( HD  or  HSCR ) is a  birth defect  in which  nerves  are missing from parts of the  intestine . [ 1 ] [ 3 ]  The most prominent symptom is  constipation . [ 1 ]  Other symptoms may include  vomiting ,  abdominal pain ,  diarrhea  and  slow growth . [ 1 ]  Most children develop signs and symptoms shortly after birth. However, others may be diagnosed later in infancy or early childhood. [ 4 ] [ 5 ]  About half of all children with Hirschsprung's disease are diagnosed in the first year of life. [ 4 ]  Complications may include  enterocolitis ,  megacolon ,  bowel obstruction  and  intestinal perforation . [ 1 ] [ 2 ]


The disorder may occur by itself or in association with other  genetic disorders  such as  Down syndrome  or  Waardenburg syndrome . [ 1 ] [ 2 ]  About half of isolated cases are linked to a specific genetic  mutation , and about 20% occur within families. [ 1 ]  Some of these occur in an  autosomal dominant  manner. [ 1 ]  The cause of the remaining cases is unclear. [ 1 ]  If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected. [ 2 ]  The condition is divided into two main types, short-segment and long-segment, depending on how much of the bowel is affected. [ 1 ]  Rarely, the  small bowel  may be affected, as well. [ 2 ]  Diagnosis is based on symptoms and confirmed by  biopsy . [ 3 ]


Treatment is generally by surgery to remove the affected section of bowel. [ 2 ]  The surgical procedure most often carried out is known as a " pull through ". [ 3 ]  Occasionally, an  intestinal transplantation  may be recommended. [ 2 ]  Hirschsprung's disease occurs in about one in 5,000 of newborns. [ 1 ]  Males are more often affected than females. [ 1 ]  The condition is believed to have first been described in 1691 by Dutch anatomist  Frederik Ruysch [ 6 ]  and is named after Danish physician  Harald Hirschsprung  following his description in 1888. [ 7 ] [ 8 ]


Typically, Hirschsprung disease is diagnosed shortly after birth, although it may develop well into adulthood,  because of the presence of  megacolon , or because the baby fails to pass the first stool ( meconium ) [ 9 ]  within 48 hours of delivery.  Normally, 90% of babies pass their first meconium within 24 hours, and 99% within 48 hours. [ 10 ]


Some other signs and symptoms in newborns include a swollen belly, vomiting (green or brown vomit), and flatulence. In older children, some other signs and symptoms include chronic constipation, flatulence, swollen belly, fatigue, and failure to thrive. [ 11 ]


Other symptoms include symptoms of bowel perforation such as vomiting, constipation, poor feeding, lethargy, and diarrhea. Symptoms of bowel obstruction would include vomiting of bile and abdominal distension. Those who do not pass stools after 36 to 48 hours after birth should raise suspicion of Hirschsprung disease. Such suspicion can also be risen if there is only passage of stools after suppository, rectal exam, or enema. Children who do not respond to constipation treatment for six months should also raise suspicion of such disease.  Enterocolitis , an acute complication of Hirschsprung disease, is characterised by sudden onset of fever, abdominal distension, vomiting, passage of bloody stools or release of explosive gas or stools after rectal examination. [ 12 ]


Some cases are diagnosed later, into childhood, but usually before age 10. [ 9 ]  The child may experience fecal retention, constipation, or abdominal distention. [ 9 ]


Hirschsprung's disease can also present as part of multi system disorders, such as: [ 13 ]


The disorder may occur by itself or in association with other  genetic disorders  such as  Down syndrome . [ 2 ]  About half of isolated cases are linked to a specific genetic  mutation  and about 20% occur within families. [ 1 ]  Some of these occur in an  autosomal dominant  manner. [ 1 ]  The cause of the remaining cases is unclear. [ 1 ]  If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected. [ 2 ]


Several  genes  and specific regions on chromosomes ( loci ) have been shown or suggested to be associated with Hirschsprung's disease [ citation needed ]


The  RET  proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region. [ 20 ]  A  proto-oncogene   can cause cancer if it is mutated or overexpressed. [ 21 ]


RET  is a gene that codes for proteins that assist  cells of the neural crest  in their movement through the digestive tract during the development of the embryo.  Those neural crest cells eventually form bundles of nerve cells called ganglions.  EDNRB  codes for proteins that connect these nerve cells to the digestive tract. Thus, mutations in these two genes could directly lead to the absence of certain nerve fibers in the colon. Research suggests that several genes are associated with Hirschsprung's disease. [ 22 ]  Also, new research suggests that mutations in genomic sequences involved in regulating  EDNRB  have a bigger impact on Hirschsprung's disease than previously thought. [ citation needed ]


RET  can mutate in many ways and is associated with Down syndrome.  Since Down syndrome is comorbid in 2% of Hirschsprung's cases, a likelihood exists that  RET  is involved heavily in both Hirschsprung's disease and Down syndrome.   RET  is also associated with  medullary thyroid cancer  and  neuroblastoma , which is a type of cancer common in children.  Both of these disorders are more common in Hirschsprung's patients than in the general population.  One function that  RE T controls is the travel of the  neural crest cells  through the intestines in the developing  fetus . The earlier the  RET  mutation occurs in Hirschsprung's disease, the more severe the disorder becomes. [ citation needed ]


Common and rare DNA variations in the neuregulin 1 ( NRG1 ) and NRG3 ( NRG3 ) were first shown to be associated with the disease in Chinese patients through a Genome Wide Association Study by the Hong Kong team in 2009  [ 23 ]  and 2012, respectively [ 24 ]  Subsequent studies in both Asian and Caucasian patients confirmed the initial findings by the University of Hong Kong. Both rare and common variants in these two genes have been identified in additional Chinese, [ 25 ]  Thai, Korean, Indonesian, and Spanish patients. These two genes are known to play a role in the formation of the enteric nervous system; thus, they are likely to be involved in the pathology of Hirschsprung's disease, at least in some cases. [ citation needed ]


Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 ( NOX5 ). [ 26 ]  This gene is located on the long arm of  chromosome 15  (15q23). [ citation needed ]


During normal  prenatal development ,  cells from the neural crest  migrate into the large intestine (colon) to form the networks of nerves called the  myenteric plexus  (Auerbach plexus) (between the  smooth muscle  layers of the gastrointestinal tract wall) and the  submucosal plexus  (Meissner plexus) (within the submucosa of the gastrointestinal tract wall). In Hirschsprung disease, the migration is not complete and part of the colon lacks these  nerve bodies  that regulate the activity of the colon. The affected segment of the  colon  cannot relax and pass  stool  through the colon, creating an obstruction. [ 27 ]


The most accepted theory of the cause of Hirschsprung is a defect in the craniocaudal migration of neuroblasts originating from the neural crest that occurs during the first 12 weeks of  gestation .  Defects in the differentiation of  neuroblasts  into ganglion cells and accelerated ganglion cell destruction within the intestine may also contribute to the disorder. [ 28 ]


This lack of ganglion cells in the myenteric and submucosal plexus is well documented in Hirschsprung's disease. [ 9 ]  With Hirschsprung's disease, the segment lacking neurons (aganglionic) becomes constricted, causing the normal, proximal section of bowel to become distended with feces. This narrowing of the distal colon and the failure of relaxation in the aganglionic segment are thought to be caused by the lack of neurons containing nitric oxide synthase. [ 9 ]


The most cited feature is absence of ganglion cells: notably in males, 75% have none in the end of the colon (rectosigmoid) and 8% lack ganglion cells in the entire colon. The enlarged section of the  bowel  is found proximally, while the narrowed, aganglionic section is found distally, closer to the end of the bowel. The absence of ganglion cells results in a persistent overstimulation of nerves in the affected region, resulting in contraction. [ citation needed ]


The equivalent disease in horses is  lethal white syndrome . [ 29 ]


Definitive diagnosis is made by suction biopsy of the distally narrowed segment. [ 30 ]  A histologic examination of the tissue would show a lack of ganglionic nerve cells. Diagnostic techniques involve  anorectal manometry , [ 31 ]   barium enema , and rectal  biopsy . The suction rectal biopsy is considered the current international  gold standard  in the diagnosis of Hirschsprung's disease. [ 32 ]


Radiologic findings may also assist with diagnosis. [ 33 ]  An abdominal x-ray can reveal a lack of stool in the large intestine or a bulging caused by blocked stool. [ 34 ]  Cineanography ( fluoroscopy  of  contrast medium  passing anorectal region) assists in determining the level of the affected intestines. [ 35 ]


Treatment of Hirschsprung's disease consists of surgical removal (resection) of the abnormal section of the colon, followed by  reanastomosis . [ citation needed ]


The first stage of treatment used to be a reversible  colostomy .  In this approach, the healthy end of the large intestine is cut and attached to an opening created on the front of the abdomen. The contents of the bowel are discharged through the hole in the abdomen and into a bag.  Later, when the patient's weight, age, and condition are right, the "new" functional end of the bowel is connected with the anus. The first surgical treatment involving surgical resection followed by reanastomosis without a colostomy occurred as early as 1933 by Doctor Baird in  Birmingham  on a one-year-old boy. [ citation needed ]


The Swedish-American surgeon  Orvar Swenson  (1909–2012), who discovered the cause of Hirschsprung's, first performed its surgical treatment, the  pull-through surgery , in 1948. [ 36 ]  The pull-through procedure repairs the colon by connecting the functioning portion of the bowel to the anus. The pull-through procedure is the typical method for treating Hirschsprung's in younger patients. Swenson devised the original procedure, and the pull-through surgery has been modified many times. [ 37 ] '


Currently,  several different surgical approaches are used, which include the Swenson, Soave, Duhamel, and Boley procedures. [ 37 ]  The Swenson procedure leaves a small portion of the diseased bowel. The Soave procedure, named after the Italian pediatric surgeon,  Franco Soave  [ it ]  (1917–1984), leaves the outer wall of the colon unaltered. The Boley procedure, pioneered by the American surgeon,  Scott Boley  (born 1941), is a small modification of the Soave procedure, so the term "Soave-Boley" procedure is sometimes used. [ 38 ] [ 39 ]   The Duhamel procedure, named for the French pediatric surgeon  Bernard Duhamel  (1917–1996), uses a  surgical stapler  to connect the good and bad bowel. [ citation needed ]


For the 15% of children who do not obtain full bowel control, other treatments are available. Constipation may be remedied by laxatives or a high-fiber diet. In those patients, serious dehydration can play a major factor in their lifestyles. A lack of bowel control may be addressed by an  ileostomy  – similar to a colostomy, but uses the end of the small intestine rather than the colon. The Malone antegrade colonic enema (ACE) is also an option. [ 40 ]  In a  Malone ACE , a tube goes through the abdominal wall to the appendix, or if available, to the colon. The bowel is then flushed daily. [ 41 ]  Children as young as 6 years of age may administer this daily flush on their own. [ citation needed ]


If the affected portion of the lower intestine is restricted to the lower portion of the rectum, other surgical procedures may be performed, such as a posterior rectal myectomy. The prognosis is good in 70% of cases. Chronic postoperative constipation is present in 7 to 8% of the operated cases. Postoperative  enterocolitis , a severe manifestation, is present in the 10–20% of operated patients. [ citation needed ]


According to a 1984 study conducted in  Maryland , Hirschsprung's disease appears in 18.6 per 100,000 live births. [ 42 ]   In Japan, it occurs at a similar rate of about one in 5,000 births (20 per 100,000). [ 43 ]  It is more common in male than female (4.32:1) and in white rather than nonwhite. [ 44 ]   Nine percent of the Hirschsprung cases were also diagnosed as having Down syndrome. [ 42 ]  Most cases are diagnosed before the patient is 10 years of age. [ 9 ]


The first report of Hirschsprung's disease dates to 1691, [ 45 ]  when it was described by  Dutch   anatomist   Frederik Ruysch . [ 46 ]  However, the disease is named after  Harald Hirschsprung , the  Danish  physician who first described two infants who died of this disorder in 1888. [ 7 ] [ 8 ]


Hirschsprung's disease is a  congenital  disorder of the colon in which certain nerve cells, known as  ganglion cells , are absent, causing  chronic   constipation . [ 47 ]  In patients with Hirschsprung disease, both myenteric and submucosal plexuses are absent. [ 48 ]  A barium enema is the mainstay of diagnosis of Hirschsprung's, though a rectal biopsy showing the lack of ganglion cells is the only certain method of diagnosis. [ citation needed ]


The first publication on an important genetic discovery of the disease was from Martucciello Giuseppe  et al.  in 1992. The authors described a case of a patient with total colonic aganglionosis associated with a 46, XX, del 10 (q11.21 q21.2) karyotype. [ 49 ]  The major gene of Hirschsprung disease was identified in this chromosomal 10 region, it was the RET proto-oncogene. [ 50 ]


The usual treatment is "pull-through" surgery where the portion of the colon that does have nerve cells is pulled through and sewn over the part that lacks nerve cells. [ 51 ]  For a long time, Hirschsprung's was considered a multifactorial disorder, where a combination of nature and nurture was considered to be the cause. However, in August 1993, two articles by independent groups in  Nature Genetics  said that Hirschsprung's disease could be mapped to a stretch of  chromosome 10 . [ 52 ] [ 53 ]


EDAR  ( EDAR hypohidrotic ectodermal dysplasia )


Hyperchlorhydria , sometimes called  chlorhydria ,  sour stomach  or  acid stomach , [ 1 ]   [ 2 ]  refers to the state in the  stomach  where  gastric acid  levels are higher than the  reference range . The  combining forms  of the name ( chlor-  +  hydr- ), referring to  chlorine  and  hydrogen , are the same as those in the name of  hydrochloric acid , which is the  active constituent  of gastric acid.


In humans, the normal  pH  is around 1 to 3, which varies throughout the day.  The highest basal secretion levels are in the late evening (around 12 A.M. to 3 A.M.).  Hyperchlorhydria is usually defined as having a pH less than 2.


In  Zollinger–Ellison syndrome   gastrin  levels are increased, leading to excess gastric acid production, which can cause  gastric ulcers . [ 3 ]
 Hypercalcemia  also increases gastrin and gastric acid and can cause ulcers. [ citation needed ]


This article about a  disease , disorder, or medical condition is a  stub . You can help Wikipedia by  expanding it .


An  ileosigmoid knot  or  compound volvulus  is an uncommon cause of  intestinal blockage . [ 1 ]  The condition arises when  ileum  loops wrap around the bottom of a redundant  sigmoid  loop. [ 2 ]  In some countries in Africa, Asia, and the Middle East, the ileosigmoid knot is a well-known ailment; this condition is uncommon in the West. [ 3 ]


Ileosigmoid knotting typically manifests as sudden, severe  abdominal pain . It can quickly worsen into  sigmoid colon  and  ileum  gangrene, which can lead to potentially fatal side effects like  sepsis , generalized  peritonitis ,  electrolyte imbalance , and  dehydration . [ 4 ]   Abdominal pain  and tenderness (100%) and distension of the abdomen (94%–100%),  vomiting  and  nausea  (87–100%), rebound tenderness (69%), as well as  shock  (0–60%) are the main symptoms and presentation indicators. [ 3 ] [ 5 ]


The ileosigmoid knot is caused by three things: eating a high-bulk diet while the  small bowel  is empty; having a long,  sigmoid colon  on a tiny pedicle; and having a long, mesentery, and freely moving  small bowel . The intestines become more mobile when a semi-liquid, heavy meal moves into the proximal  jejunum , and the heavier sections of the  jejunum  fall to the left lower quadrant. Around the base of the narrow  sigmoid colon , the empty loops of the  ileum  and distal  jejunum  rotate in a clockwise direction. With two closed-loop obstructions—one in the small bowel and the other in the  sigmoid colon —further  peristalsis  creates an ileosigmoid knot. [ 6 ]


Even though radiographic findings indicate colonic obstruction, which is uncommon in small bowel obstruction, clinical features like  vomiting  point to  small bowel obstruction . [ 7 ]  Ileosigmoid knotting is frequently confused radiographically with a straightforward  sigmoid volvulus . On the other hand, in contrast to  sigmoid volvulus , attempts to deflate the enlarged colon with a flatus tube or  sigmoidoscope  frequently fail and may even be hazardous in ileosigmoid knotting. This is because the ileum firmly encloses the sigmoid colon's base, thwarting any such attempt. [ 4 ]  These three characteristics—the inability to insert a  sigmoidoscope , radiographic evidence of primarily  large bowel obstruction , and the clinical picture of small  bowel obstruction —might make up a helpful diagnostic triad. [ 8 ]


Due to their unfamiliarity, the radiographic findings of ileosigmoid knotting—which include multiple air-fluid levels in the small intestine and a double loop of dilated sigmoid shadow—are only occasionally described. [ 9 ] [ 10 ]


The descending colon, medial deviation of the cecum, and "the whirl sign," which is produced by the twisted  intestinal tract  and sigmoid mesocolon in ileosigmoid knot, are findings in a  CT scan  that are suggestive of ileosigmoid knotting. Furthermore, some have observed the radial distribution of the mesenteric vasculature and the intestine and believe this to be useful diagnostic data. [ 4 ]


Ileosigmoid knotting has been classified into the three types listed below: [ 4 ]


Type 1:  The  ileum , which is the active component, encircles the  sigmoid colon , which is the passive component, either clockwise or counterclockwise (type A when clockwise and type B when counterclockwise). [ 4 ]


Type 2:  In either a clockwise or counterclockwise direction, the  sigmoid colon , the active component, encircles an  ileum  loop, the passive component. [ 4 ]


Type 3:  The  sigmoid colon  (passive component) is encircled by the  ileocecal  segment (active component). [ 4 ]


Aggressive resuscitation with fluid and  electrolytes , along with the correction of any  acid-base imbalance , are the initial management measures. The earliest possible surgical intervention should be performed following hemodynamic stabilization. After the procedure, appropriate  antibiotic  therapy is started as soon as possible and is continued for 5-7 days.  Metronidazole ,  aminoglycosides , and  cephalosporins  are the typical  antibiotic  combinations. [ 4 ]


Males account for 80.2% of cases of ileosigmoid knotting, with a mean age of 40 years (range: 4-90 years). The literature indicates the presence of additional secondary causative factors in addition to the aforementioned anatomic prerequisites, such as late pregnancy,  Meckel's diverticulitis  with a band, trans mesenteric  herniation , floating  cecum , and ileocecal  intussusceptions . [ 6 ]


Ileosigmoid knotting is uncommon in the white population, although it is primarily documented in some African, Asian, and Middle Eastern countries. [ 11 ]


E Parker is credited with describing the first case of ileosigmoid knotting in 1846. [ 12 ]


Impaction  is  bowel obstruction  that can occur in various kinds of  animals  when they consume something that they cannot  digest , typically  substrate . Once the substance is ingested it will block the  digestive tract  and, if untreated, cause death.


Some symptoms include a lack of appetite or  lethargy . On many reptiles a large blue seemingly bruised spot will be visible in the  abdomen ; however, this only shows through if the skin on the species is clear enough to see the lower internal organs. [ 1 ]


Common treatments involve placing the reptile in a lukewarm bath and gently rubbing the area under the impaction to help the passing of the consumed substance. Place both thumbs on the back at the middle, put the first two fingers of the hand under the belly and rub gently in a circular way until the reptile defecates. If this fails, the animal must have an  enema . [ 1 ]


Indolent T cell lymphoproliferative disorder of the gastrointestinal tract  or  Indolent T cell lymphoproliferative disorder of the GI tract  (ITCLD-GT) is a rare and recently recognized disorder in which mature  T cell  lymphocytes accumulation abnormally in the gastrointestinal tract (GI tract). [ 1 ]  This accumulation causes various lesions (e.g.  polyps , thickened mucosal folds, small areas of redness, and superficial ulcerations) in the  mucosal  layer lining the GI tract. Individuals with ITCLD-GT commonly complain of chronic  GI tract symptoms  such as nausea, vomiting, diarrhea, abdominal pain, and  rectal bleeding . [ 2 ]


Carbonnell et al. [ 3 ]  first described a case of an indolent GI tract lymphoproliferation disorder in 1994 and defined the lymphocytes involved in it to be T cells expressing the  CD4   glycoprotein  on their  surface membranes . Subsequent studies reported on patients who had a similar indolent GI tract disorder that involved T cells which expressed either the CD4,  CD8 , or neither surface membrane glycoprotein. The disorder resembled certain aggressive GI tract lymphomas and was variably termed  indolent  lymphoma  or indolent T cell lymphoproliferative disorder of the gastrointestinal tract. [ 4 ]  However, the disease differed from the aggressive lymphomas which it mimicked in having a prolonged and usually non-progressive course. Furthermore, the disorder's lesions consisted of normal-appearing T cells that proliferated very slowly and usually caused little or no tissue destruction. [ 5 ]  In 2017, the  World Health Organization  provisionally classified ITCLD-GT as an extranodal (i.e. usually not involving  lymph nodes ), indolent disorder in which various subtypes of T cells proliferate in the GI tract. [ 6 ]


While usually acting like a benign disease, ITCLD-GT has malignant features:  1)  its normal-appearing T cells are  clonal  in nature, i.e. descended from a single cell; [ 6 ]   2)  these T cells may contain genetic abnormalities [ 7 ]  that are known to occur in and contribute to the development of very aggressive lymphomas; [ 8 ]  and  3)  ITCLD-GI, after many years of indolent behavior, may progress to an aggressive lymphoma. [ 2 ]  Thus, ITCLD-GT can act as a  premalignat disorder . Nonetheless, most cases of it run an indolent, non-malignant course and when mistakenly treated as an aggressive lymphoma, do not responded to standard  chemotherapy  treatments. [ 5 ]  The disorder has also been mistaken for, and found unresponsive to therapies that treat  inflammatory  or  autoimmune  bowel diseases. [ 1 ] [ 4 ]  Clinically, ITCLD-GT must be distinguished from the malignant, inflammatory, and autoimmune bowel diseases that it mimics in order to avoid useless and potentially harmful therapies. [ 5 ]


ITCLD-GT occurs more commonly in males of middle age (median age 48.4, range 15–77 years in one study). [ 2 ]  Individuals with the disease present with GI tract symptoms which often are serious and/or debilitating [ 9 ]  and may mimic those occurring in malignant lymphoproliferative, inflammatory, or autoimmune bowel diseases. [ 4 ]  These symptoms include chronic  epigastric  pain, abdominal pain, heartburn, nausea, diarrhea, vomiting, weight loss, relapsing oral ulcers, relapsing colorectal ulcers, rectal bleeding, and/or  night sweats . [ 4 ]  Several patients presenting with these symptoms have been diagnosed with and unsuccessfully treated for  peripheral T-cell lymphoma , [ 5 ]  an inflammatory bowel disease (either  Crohn disease  or  ulcerative colitis ), [ 1 ]  or the autoimmune GI tract disorder, celiac disease. [ 10 ]  It has been shown or appears very likely that these patients had ITCLD-GT rather than the cited diagnoses. [ 1 ] [ 5 ] [ 10 ]


Most patients with ITCLD-GT have chronic, relapsing and recurring GI tract symptoms that persist over many years. In one retrospective study, 19 of 23 patients with CD4+ ITCLD-GT had persistent disease over a follow-up period of 1–14 years (median 4.8 years), 2 of 23 patients had clinical and morphologic (i.e. negative GI tract evaluations) remissions enduring for at least 5–7 years, and 1 of 23 patients developed and died from a  large-cell lymphoma  of undetermined type. In the same study, 10 of 10 patients with CD8+ ITCLD-GT had persistent disease that had not progressed to a malignancy over an observation period of 1–18 years (median 2 years) although one patient had developed bone marrow involvement and therefore may have had disease which was in the process of transforming to a malignant state. [ 4 ]  Other reports have found that the disorder in one patient with CD4-, CD8- ITCLD-GT disease progressed to involve the liver [ 5 ]  and the disorder in two patients with CD4+ ITCLD-GT disease progressed to an undetermined type of  large T-cell lymphoma . [ 9 ]  In another retrospective analysis, 6 of 34 (17.6%) patients with ITCLD-GT progressed to a malignant state as evidenced by its spread to the blood or bone marrow: 2 (5.6%) patients died as a direct result of this spreading. [ 2 ]


The lesions in ITCLD-GT consists of slowly growing, mature, and benign-appearing T cells. The reasons for their accumulations in the GI tract are unclear. However, these cells often carry potentially  oncogenic  mutations. In a recent study, the T cells in 4 of 5 patients with CD4+ T-cell disease carried a  STAT3 - JAK2   fusion gene . [ 6 ]  This gene consists of a fusion between the  STAT3  gene at position 2.2 on the long (or "g") arm of  chromosome 17  (location abbreviated 17q21.2) and the  JAK2  gene at position 24.1 on the short ("q") of  chromosome 9  (9p24.1). The disorder in two of the patients with this t(9;17)(p24.1;q21/2) fusion gene progressed to malignant lymphomas. [ 9 ]  Abnormalities in the expression and/or activity of  STAT3  and  JAK2 [ 11 ]  as well as various  JAK2  fusion genes [ 9 ]  are associated with the development and progression of various  myeloproliferative  and lymphoproliferative malignancies. These findings suggest that the  STAT3-JAK2 -fusion gene may contribute to the malignant progression and perhaps development of CD4+ ITCLD-GT. [ 9 ]  Numerous other genetic abnormalities occur in the T-cells of ITCLD-GT but unlike the  STAT3-JAK  fusion gene have been limited to single cases. These abnormalities include  trisomy  of  chromosome 5 , a t(4;16)(q26;p13) fusion between  interleukin-2  and  B-cell maturation antigen  genes, loses in the 4p26 and 16p13 chromosomal areas involved in formation of the t(4;16)9q26;p13) fusion gene, and one or more  copy number variations  in diverse areas of different chromosomes. [ 4 ]  The role(s), if any, of these abnormalities in ITCLD-GT is unclear. [ citation needed ]


The cells involved in all cases of ITCLD-GT are mature T cells [ 1 ]  that exhibit a clonal rearrangement of their  T-cell receptors  and, therefore, are derived from a common ancestry cell. [ 4 ]  They express the  αβ  as opposed to the  γδ  surface membrane T-cell receptor and therefore are αβ rather than  γδ T-cells . In all reported cases, these T cells express the  CD3   cluster of differentiation   protein complex  but vary in their expression of the CD4 cluster of differentiation glycoprotein as well as the  CD8  glycoprotein component of the T cell receptor. Individuals with ITCLD-GT, therefore, have pathological accumulations of either CD4+, CD8+, or, very rarely, CD4-, CD8- T cells. [ 4 ]  A single case of CD4+, CD8+ T cell disease has been reported recently. [ 9 ]  There may be differences in the presentation, course, and malignant potential of ITCLD-GT based or these different expressions of CD4 and CD8 but this requires further study. Unlike certain types of T cell lymphomas for which it has been mistaken, the T cells in ITCLD-GT do not express the neutral cell  adhesion molecule ,  CD56 , and are not infected with the  Epstein–Barr virus  and therefore do not express this virus's  latency proteins  or  latency ncRNAs . [ 1 ]  The origin of these cells is unknown but it is thought that the CD4+ and CD8+ T-cells derive from mucosal  T helper  and  cytotoxic T  lymphocytes, respectively. The CD4-, CD8- T cells that may cause rare cases of the disorder exhibit  cytology  and  morphology  features of both of the latter two mucosal cell types. [ 4 ]


Histological  analysis of tissues biopsied from the GI tract generally reveals dense infiltrates of small, mature lymphocytes in the mucosa that may displace [ 2 ]  but usually do not invade [ 4 ]  the  epithelium ; these cells sometimes extend through the  muscularis mucosa  to invade the  submucosa . [ 4 ]  The lesions may contain reactive  plasma cells ,  eosinophils ,  granulomas  (in CD4+ disease), and  lymphoid follicles . [ 2 ]  There is little or no tissue destruction. [ 1 ]  Immunohistochemistry analyses indicate that the small lymphocytes are CD4+, [ 9 ]  CD8+, [ 9 ]  CD4-/CD8-, [ 4 ]  or CD4+/CD8+ T-cells [ 9 ]  that stain for CD3 [ 4 ]  but not CD56 or Epstein-Barr virus products. [ 1 ]  Notably, the affected T cells have an extremely low rate of proliferation as determined by examining their  KI-67 protein  using  immunofluorescence  analysis. [ 4 ]


The diagnosis of indolent T cell lymphoproliferative disorder of the GI tract depends on identifying the presentation, clinical course, and laboratory and histological findings given in the previous four sections. [ 4 ]  (Future studies may find that the diagnosis is supported by demonstrating the presence of the  STAT3-JAK2  fusion gene in the CD4+ T cells of suspicious tissues. [ 6 ] )


Inspection of the entire GI tract by  endoscopy  and  colonoscopy  generally finds  mucosal   redness , erosions, small superficial ulcerations, occasional small  polyps , [ 2 ]   fissures ,  diverticula , and, rarely, tumor-like masses and deep ulcers. [ 4 ]  These lesions may be localized, occur in multiple sites, or extend throughout the GI tract; [ 4 ]  they are more common in the small intestine and colon [ 2 ]  but can also occur in the stomach,  esophagus , oral cavity (e.g.  palate ), and rectum. [ 4 ]  Whole body  computed tomography scans  (i.e. CT scans) frequently find enlarged  mesenteric lymph nodes  (i.e. lymph nodes attached to the intestinal  mesentery ) and may show evidence of liver, spleen, and/or other organ involvement in cases which are advancing or have advanced to a malignant lymphoma.  Positron emission tomography  scans (i.e. PET scans) and  positron emission tomography–computed tomography  scans (i.e. PET-CT scans) likewise often show that the mesenteric lymph nodes in ITCLD-GT exhibit modestly increased  metabolic  or  biochemical  activity and, in cases of progressing or overt malignant disease, show increased activity in other organs. [ 4 ]  Inspection of patients'  peripheral blood smearss  and  bone marrow tissues  may identify excessive numbers of ITCLD-GT's T cells and thereby likewise indicate progressing or malignant disease. [ 2 ]


Because of the radical differences in their prognoses and treatments, ITCLD-GT should be distinguished from the malignant, inflammatory, autoimmune, and other diseases that it can mimic. [ citation needed ]  Key findings that distinguish ITCLD-GT from the following major diseases which ITCLD-GT may mimic are:


Studies indicate that patients with ITCLD-GT should be treated conservatively. Chemotherapy regimens directed at malignant lymphoma and treatment regimens used to treat celiac disease, Crohn's disease, or ulcerative colitis have had little or no beneficial effects on the course of the disease. [ 4 ]  Patients should be follow regularly with peripheral blood and bone marrow examinations, GI tract endoscopic examinations [ 4 ]  and PET scans [ 2 ]  in order to detect the progression of ITCLD-GT to a malignant phase.


Studies to date [ when? ]  indicate that most patients experience a prolonged course of persistent or recovering-relapsing GI tract symptoms. A small percentage of patients have had spontaneous and sustained recoveries or progressed to a malignant lymphoma. [ 4 ]


Inflammatory bowel disease  ( IBD ) is a group of  inflammatory  conditions of the  colon  and  small intestine , with  Crohn's disease  and  ulcerative colitis  (UC) being the principal types. [ 3 ]  Crohn's disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas UC primarily affects the colon and the rectum. [ 4 ] [ 5 ] [ 6 ]


In spite of Crohn's and UC being very different diseases, both may present with any of the following symptoms: abdominal pain,  diarrhea ,  rectal bleeding , severe internal cramps/muscle spasms in the region of the pelvis and  weight loss .  Anemia  is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD). [ 9 ] [ 10 ]  Associated complaints or diseases include  arthritis ,  pyoderma gangrenosum ,  primary sclerosing cholangitis , and  non-thyroidal illness syndrome  (NTIS). [ 11 ]  Associations with  deep vein thrombosis  (DVT) [ 12 ]  and  bronchiolitis obliterans organizing pneumonia  (BOOP) have also been reported. [ 13 ]  Diagnosis is generally by assessment of inflammatory markers in stool followed by  colonoscopy  with  biopsy  of pathological lesions. [ 14 ]


IBD is a complex disease which arises as a result of the interaction of environmental and genetic factors leading to immunological responses and inflammation in the intestine. [ 4 ]


People living with IBD are very interested in diet, but little is known about the impact of diet on these patients. Recent reviews underlined the important role of nutritional counselling in IBD patients. Patients should be encouraged to adopt diets that are best supported by evidence and involve monitoring for the objective resolution of inflammation. [ 22 ] [ 23 ]


A 2022 study found that diets with increased intake of fruits and vegetables, reduction of processed meats and refined carbohydrates, and preference of water for hydration were associated with lower risk of active symptoms with IBD, although increased intake of fruits and vegetables alone did not reduce risk of symptoms with Crohn's disease. [ 24 ]  A 2022 scientific review also found generally positive outcomes for IBD patients who adhered to the Mediterranean diet (high fruit and vegetable intake). [ 25 ]


Dietary patterns are associated with a risk for ulcerative colitis. In particular, subjects who were in the highest  tertile  of the  healthy dietary pattern  had a 79% lower risk of ulcerative colitis. [ 26 ]


Gluten sensitivity  is common in IBD and associated with having flareups. Gluten sensitivity was reported in 23.6% and 27.3% of Crohn's disease and ulcerative colitis patients, respectively. [ 27 ]


A  diet  high in  protein , particularly animal protein, and/or high in sugar may be associated with increased risk of IBD and relapses. [ 28 ] [ 29 ]


Emerging evidence indicates that  bile acids  are important etiological agents in IBD pathogenesis. [ 30 ]  IBD patients have a consistent pattern of an increased abundance of primary bile acids such as  cholic acid  and  chenodeoxycholic acid  (and their conjugated forms), and a decreased abundance of secondary bile acids such as  lithocholic acid  and  deoxycholic acid . [ 30 ]