A  phytobezoar  is a type of  bezoar , or trapped mass in the gastrointestinal system, that consists of components of indigestible plant material, such as fibres, skins and seeds. While phytobezoars may be discovered incidentally on  barium x-ray  or  endoscopic  testing of the stomach, individuals with phytobezoars may develop symptoms: nausea, vomiting,  gastric outlet obstruction , perforation, abdominal pain, and  bleeding  have been reported. [ 1 ]  Conditions that lead to decreased motility in the stomach ( gastroparesis ) and surgeries on the stomach (such as  vagotomy  or  gastric bypass ) are associated with the development of phytobezoars. [ 2 ]   A specific type of phytobezoar, termed a  diospyrobezoar , is associated with ingestion of unripe  persimmons , which contain a soluble  tannin  called shibuol that  polymerizes  into a coagulative cellulose-protein compound in the acid environment of the stomach, to form the bezoar. [ 3 ]   In addition to their presence in human stomachs, phytobezoars have been documented in the stomachs of slaughtered plant-eating animals. [ 1 ]


Gastric phytobezoars are a form of  intestinal blockage  and are seen in those with poor gastric motility. The preferred treatment of bezoars includes different therapies and/or fragmentation to avoid surgery. Phytobezoars are most common and consist of undigested lignin, cellulose,  tannins, celery, pumpkin skin, grape skins, prunes, raisins, vegetables and fruits. [ 4 ]  Phytobezoars can form after eating persimmons and pineapples. These are more difficult to treat and are referred to as diospyrobezoars. [ 5 ]  Phytobezoars are more likely to form due to the ingestion of raw plant foods, even in persons without predisposing factors, as cooking softens them for easier digestion. [ 6 ]


Several treatments for phytobezoars have been described.  Endoscopy  involves using a fibre-optic flexible camera to identify the phytobezoar, that can be evacuated from the stomach using various assisted devices (such as  Roth baskets , snares, or Dormia baskets). [ 1 ] [ 3 ]  If the phytobezoar cannot be removed due to size, electrohydraulic  lithotripsy , mechanical  lithotripsy , snares, or  Nd:YAG laser  therapy may be used to fragment the mass. [ 3 ]   Papain  (meat tenderizer) and  cellulase  enzymes have been used to help reduce the size of phytobezoars. [ 3 ]   Carbonated soda  ingestion has also been found to be useful to decrease the size of diospyrobezoars. [ 3 ] [ 7 ]  A systematic review regarding initial treatment of phytobezoars with  Coca-Cola  found that Coca-Cola alone completely dissolved phytobezoars in half of cases, and that Coca-Cola combined with other endoscopic methods (particularly endoscopic fragmentation) was successful more than 90% of the time. [ 7 ]  The same review found that diospyrobezoars (which are considered more difficult to dissolve because of their hard consistency) were successfully treated with Coca-Cola alone in only 23% of cases, but that follow-up endoscopic fragmentation was successful in 84.6% of cases in the publications reviewed. [ 7 ]  When all other measures have failed, surgical  gastrotomy  is required to evacuate the bezoar. [ 8 ]


Generally, bezoars can be found in the stomach in less than 0.5% of patients having an  esophagogastroduodenoscopy . [ 4 ]  The formation of diospyrobezoars from persimmons is due to a chemical reaction between stomach acid and  phlobatannin  contained in the persimmon. [ 9 ]  Tannin and shibuol found in the skin of unripe persimmons reacts with gastric acid and  forms a coagulum. This structure then accumulates cellulose, hemicellulose and protein. [ 5 ]


In  medicine ,  pink lady  is a term used for a combination of medications used to treat  gastroesophageal reflux  or  gastritis . It usually consists of an  antacid  and the  anaesthetic   lidocaine .  Some variants contain an  anticholinergic .  The name of the preparation comes from its  colour  –  pink .


Pink ladies often relieve symptoms for  gastro-esophageal reflux disease  (GERD).  However, they are generally believed to be insufficient to  diagnose  GERD and rule-out other causes of  chest pain  and/or  abdominal pain  such as  myocardial infarction  (heart attack). [ 1 ]


The pink lady is the de facto term describing xylocaine viscous and a liquid antacid given  by mouth  to treat  emergency department  patients and help determine if the chest pains are either heart or digestive related.  If esophageal symptoms subside the treatment may indicate the symptoms are non-cardiac. [ 2 ]


Polyposis registries  exists for the purpose of understanding the  genetic disease   familial adenomatous polyposis . [ 1 ]  The registries provide a service to doctors for identification, surveillance and management of families and individuals with high  colorectal cancer  risk from  Familial Adenomatous Polyposis  (FAP) and  Hereditary Non-Polyposis Colorectal Cancer  (HNPCC). The  Centers for Disease Control and Prevention  of the United States provides,  royalty-free ,  Registry Plus  software for collecting and processing cancer registry data compliant with national standards established by  health professionals  and regulators to understand and address the burden of cancer more effectively.


Polyposis  registries have been used in numerous  academic studies  to assess  morbidity  and  mortality  of  colorectal cancer  related to  FAP , and use of registry data has resulted in improved treatment and reduced mortality from polyposis-related colorectal cancer.


The  University of Texas M. D. Anderson Cancer Center  maintains an international  list of registries  related to  hereditary colon cancer .


Some of the registries include: -


Postpolypectomy coagulation syndrome  ( Postpolypectomy syndrome  or  PPCS ) is a condition that occurs following  colonoscopy  with  electrocautery   polypectomy , which results in a burn injury to the wall of the  gastrointestinal tract . The condition results in  abdominal pain ,  fever ,  elevated white blood cell count  and elevated serum  C-reactive protein .


PPCS causes abdominal pain and fever. [ 3 ]  The condition usually onsets within 1–5 days after colonoscopy with polypectomy using electrocautery. [ 3 ]  Physical examination may show evidence of peritonitis. [ 3 ]


PPCS is caused by an electrocautery-induced injury to the wall of the colon that occurs during removal of colon polyps. [ 3 ]  PPCS occurs when the electric current extends beyond the mucosa, entering the muscularis propria and serosa, resulting in a full thickness (transmural) burn injury. [ 1 ]  The transmural burn results in localized inflammation of the peritoneum (peritonitis). [ 3 ]


PPCS may resemble perforation. Recognition of PPCS is important, since treatment usually does not require surgery, unlike gastrointestinal perforation. Laboratory studies may show elevated white blood cell count ( leukocytosis ) and elevated inflammatory markers such as  C-reactive protein . CT scan of the abdomen may show severe mural thickening, without air present outside the gastrointestinal tract. [ 4 ]


Treatment of PPCS consists of intravenous fluids, antibiotics, and avoiding any oral intake of food, water, etc. until symptoms improve. [ 3 ]


Some low quality evidence suggests that antibiotic prophylaxis may prevent PPCS. [ 2 ]


PPCS occurs about 1% of cases following polypectomy with electrocautery. [ 5 ] [ 1 ]  Risk factors for PPCS include right colon polypectomy, large polyp size (>2 cm), non-polypoid lesions (laterally spreading lesions), and hypertension. [ 1 ]


Proton-pump inhibitors  ( PPIs ) are a class of  medications  that cause a profound and prolonged reduction of  stomach acid  production. They do so by irreversibly inhibiting the stomach's  H + /K +  ATPase   proton pump . [ 1 ]  The body eventually synthesizes new proton pumps to replace the irreversibly inhibited ones, a process driven by normal cellular turnover, which gradually restores acid production. [ 2 ]


Proton-pump inhibitors have largely superseded the  H 2 -receptor antagonists , a group of medications with similar effects but a different mode of action, and heavy use of  antacids . [ 3 ]  A  potassium-competitive acid blocker  (PCAB)  revaprazan  was marketed in Korea as an alternative to a PPI. A newer PCAB  vonoprazan  with a faster and longer lasting action than revaprazan, and PPIs has been marketed in Japan (2013), Russia (2021), and the US (2023). [ 4 ] [ 5 ] [ 6 ]


PPIs are among the most widely sold medications in the world. The class of proton-pump inhibitor medications is on the  World Health Organization's List of Essential Medicines . [ 7 ] [ 8 ]   Omeprazole  is the specific listed example. [ 7 ] [ 8 ]


These medications are used in the treatment of many conditions, such as:


Specialty professional organizations recommend that people take the lowest effective PPI dose to achieve the desired therapeutic result when used to treat gastroesophageal reflux disease long-term. [ 20 ] [ 21 ] [ 22 ]  In the United States, the  Food and Drug Administration  (FDA) has advised that over-the-counter PPIs, such as Prilosec OTC, should be used no more than three 14-day treatment courses over one year. [ 23 ] [ 24 ]


Despite their extensive use, the quality of the evidence supporting their use in some of these conditions is variable. The effectiveness of PPIs has not been demonstrated for every case. For example, although they reduce the incidence of  esophageal adenocarcinoma  in Barrett's oesophagus, [ 16 ]  they do not change the length affected. [ 25 ]  In addition, research in the UK has suggested that PPIs are not effective at treating persistent throat symptoms. [ 26 ] [ 27 ]


PPIs are often used longer than necessary. In about half of people who are hospitalized or seen at a primary care clinic there is no documented reason for their long-term use of PPIs. [ 28 ]  Some researchers believe that, given the little evidence of long-term effectiveness, the cost of the medication and the potential for harm means that clinicians should consider stopping PPIs in many people. [ 29 ]


In general, proton pump inhibitors are well tolerated, and the incidence of short-term adverse effects is relatively low. The range and occurrence of  adverse effects  are similar for all of the PPIs, though they have been reported more frequently with  omeprazole . This may be due to its longer availability and, hence, clinical experience. [ citation needed ]


Common adverse effects include  headache ,  nausea ,  diarrhea ,  abdominal pain ,  fatigue , and  dizziness . [ 30 ]  Infrequent adverse effects include  rash ,  itch ,  flatulence ,  constipation ,  anxiety , and  depression . Also infrequently, PPI use may be associated with occurrence of  myopathies , including the serious reaction  rhabdomyolysis . [ 31 ]


Long-term use of PPIs requires assessment of the balance of the  benefits and risks  of the therapy. [ 32 ] [ 33 ] [ 34 ] [ 35 ]  As of March 2017, various adverse outcomes have been associated with long-term PPI use in several primary reports, but reviews assess the overall quality of evidence in these studies as "low" or "very low". [ 34 ]   They describe inadequate evidence to establish  causal relationships  between PPI therapy and many of the proposed associations, due to study design and small estimates of effect size. [ 35 ]


As of March 2017, benefits outweighed risks when PPIs are used appropriately, but when used inappropriately, modest risks become important. [ 34 ] [ 36 ]  They recommend that PPIs should be used at the lowest effective dose in people with a proven indication, but discourage dose escalation and continued chronic therapy in people unresponsive to initial empiric therapy. [ 35 ]


With regard to iron and vitamin B 12 , the data is weak and several  confounding factors  have been identified. [ 33 ]   Low levels of magnesium  can be found in people on PPI therapy and these can be reversed when they are switched to  H 2 -receptor antagonist  medications. [ 33 ] [ 37 ] [ 24 ]


High dose or long-term use of PPIs carries an increased risk of  bone fractures  which was not found with short-term, low dose use; the FDA included a warning regarding this on PPI drug labels in 2010. [ 23 ]


In infants, acid suppression therapy is frequently prescribed to treat symptomatic gastroesophageal reflux in otherwise healthy infants (that is: without gastroesophageal reflux disease). A study from 2019 showed that  PPI use alone and together with histamine H2-receptor antagonists was associated with an increased bone fracture hazard, which was amplified by days of use and earlier initiation of therapy. [ 38 ]  The reason is not clear; increased bone break down by  osteoclasts  has been suggested. [ 39 ]


A recent 2024 study published in the  Journal of Clinical Endocrinology & Metabolism  found that chronic use of PPIs in men is linked to lower trabecular bone quality. [ 40 ]  Specifically, PPI use was associated with reduced lumbar spine trabecular bone score (TBS), as well as lower bone mineral density (BMD) T-scores in the lumbar spine, total hip, and femoral neck. [ 41 ]  These findings suggest that long-term PPI use may negatively affect bone health in men.


Some studies have shown a correlation between use of PPIs and  Clostridioides difficile  infection . While the data are contradictory and controversial, the FDA had sufficient concern to include a warning about this adverse effect on the label of PPI medications. [ 33 ]  Concerns have also been raised about  spontaneous bacterial peritonitis  (SBP) in older people taking PPIs and in people with  irritable bowel syndrome  taking PPIs; both types of infections arise in these populations due to underlying conditions and it is not clear if this is a class effect of PPIs. [ 33 ]  PPIs may predispose an individual to developing   small intestinal bacterial overgrowth  or fungal overgrowth. [ 42 ] [ 43 ]


In  cirrhotic patients , large volume of ascites and reduced esophageal motility by varices can provoke  GERD . [ 44 ] [ 45 ] [ 46 ]  Acidic irritation, in return, may induce the rupture of varices. [ 47 ]  Therefore, PPIs are often routinely prescribed for cirrhotic patients to treat GERD and prevent variceal bleeding. However, it has been recently shown that long term use of PPIs in patients with  cirrhosis  increases the risk of SBP and is associated with the development of clinical decompensation and liver-related death during long-term follow-up. [ 48 ]


There is evidence that PPI use alters the composition of the bacterial populations inhabiting the  gut , the  gut microbiota . [ 49 ]  Although the mechanisms by which PPIs cause these changes are yet to be determined, they may have a role in the increased risk of bacterial infections with PPI use. [ 50 ]  These infections can include  Helicobacter pylori  due to this species not favouring an acid environment, leading to an increased risk of ulcers and gastric cancer risk in genetically susceptible patients. [ 50 ]


PPI use in people who have received attempted  H. pylori  eradication may also be associated with an increased risk of gastric cancer. [ 51 ]  The validity and robustness of this finding, with the lack of causality, have led to this association being questioned. [ 52 ]   It is recommended that long-term PPIs should be used judiciously after considering individual's risk–benefit profile, particularly among those with history of  H. pylori  infection, and that further, well-designed, prospective studies are needed. [ 53 ]


Long-term use of PPIs is associated with the development of benign  polyps  from  fundic glands  (which is distinct from  fundic gland polyposis ); these polyps do not cause cancer and resolve when PPIs are discontinued. [ 33 ]  There is concern that use of PPIs may mask  gastric  cancers or other serious gastric problems. [ 33 ]


PPI use has also been associated with the development of  microscopic colitis . [ 54 ]


Associations of PPI use and cardiovascular events have also been widely studied but clear conclusions have not been made as these relative risks are confounded by other factors. [ 55 ] [ 56 ]  PPIs are commonly used in people with cardiovascular disease for gastric protection when  aspirin  is given for its antiplatelet actions. [ 55 ] [ 57 ]  An interaction between PPIs and the metabolism of the platelet inhibitor  clopidogrel  is known and this drug is also often used in people with cardiac disease. [ 58 ] [ 59 ] [ 22 ]  There are associations with an increased risk of stroke, but this appears to be more likely to occur in people who already have an elevated risk. [ 60 ]


One suggested mechanism for cardiovascular effects is because PPIs bind and inhibit  dimethylargininase , the enzyme that degrades  asymmetric dimethylarginine  (ADMA), resulting in higher ADMA levels and a decrease in bioavailable  nitric oxide . [ 61 ]


A 2022 umbrella review of 21 meta-analyses shows an association between proton-pump inhibitor use and an increased risk of four types of cancer. [ 62 ]


Associations have been shown between PPI use and an increased risk of pneumonia, particularly in the 30 days after starting therapy, where it was found to be 50% higher in community use. [ 63 ] [ 64 ]  Other very weak associations of PPI use have been found, such as with  chronic kidney disease , [ 65 ] [ 66 ] [ 67 ] [ 22 ] [ 68 ] [ 69 ]   dementia [ 70 ] [ 34 ] [ 71 ]  and  Hepatocellular carcinoma  (HCC). [ 72 ]


As of 2016, results were derived from observational studies, it remained uncertain whether such associations were causal relationships. [ 34 ] [ 35 ] [ 73 ]


Proton pump  inhibitors act by irreversibly blocking the  hydrogen / potassium   adenosine triphosphatase   enzyme  system (the  H + /K +  ATPase , or, more commonly, the gastric proton pump) of the gastric  parietal cells . [ 74 ]  The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H +  ions into the gastric lumen, making it an ideal target for inhibiting acid secretion. [ citation needed ]  Because the H,K-ATPase is the final step of acid secretion, an inhibitor of this enzyme is more effective than receptor antagonists in suppressing gastric acid secretion. [ 75 ]  All of these drugs inhibit the gastric H,K-ATPase by covalent binding, so the duration of their effect is longer than expected from their levels in the blood. [ 76 ]


Targeting the terminal step in acid production, as well as the  irreversible  nature of the inhibition, results in a class of medications that are significantly more effective than  H 2  antagonists  and reduce gastric acid secretion by up to 99%. [ 77 ]


Decreasing the acid in the stomach can aid the healing of  duodenal  ulcers and reduce the pain from indigestion and  heartburn . However,  stomach acids  are needed to digest proteins, vitamin B 12 , calcium, and other nutrients, and too little stomach acid causes the condition  hypochlorhydria . [ citation needed ]


The PPIs are given in an inactive form, which is neutrally charged ( lipophilic ) and readily crosses  cell membranes  into intracellular compartments (like the parietal cell canaliculus) with acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will  covalently  and irreversibly bind to the gastric proton pump, deactivating it.


In  H. pylori  eradication , PPIs help by increasing the stomach pH, causing the bacterium to shift out of its coccoid form which is resistant to both acids and antibiotics. PPIs also show some weaker additional effects in eradication. [ 78 ]


The rate of omeprazole absorption is decreased by concomitant food intake. [ 79 ]  In addition, the absorption of lansoprazole and esomeprazole is decreased and delayed by food. It has been reported, however, that these  pharmacokinetic  effects have no significant impact on efficacy. [ 80 ] [ 81 ]


In healthy humans, the half-life of PPIs is about 1 hour (9 hours for  tenatoprazole ), but the duration of acid inhibition is 48 hours because of irreversible binding to the H,K-ATPase. [ 82 ]  All the PPIs except tenatoprazole are rapidly metabolized in the liver by CYP enzymes (mostly by CYP2C19 and 3A4). [ 82 ]  Dissociation of the inhibitory  complex  is probably due to the effect of the  endogenous   antioxidant   glutathione  which leads to the release of omeprazole sulfide and reactivation of the enzyme. [ 83 ] [ 84 ]


Medically used proton pump inhibitors: [ citation needed ]


There is no clear evidence that one proton pump inhibitor works better than another. [ 1 ] [ 89 ]


PPIs were developed in the 1980s, with omeprazole being launched in 1988. Most of these medications are  benzimidazole  derivatives, related to omeprazole, but  imidazopyridine  derivatives such as  tenatoprazole  have also been developed. [ 77 ]  Potassium-competitive inhibitors such as  revaprazan  reversibly block the potassium-binding site of the proton pump, acting more quickly, but are not available in most countries. [ 90 ]


In  British Columbia, Canada  the cost of the PPIs varies significantly from  CA$0.13  to  CA$2.38  per dose [ 91 ]  while all agents in the class appear more or less equally effective. [ 1 ] [ 89 ]


A comparative table of  FDA -approved indications for PPIs is shown below.


Gastric acid is important for breakdown of food and release of  micronutrients , and some studies have shown possibilities for interference with absorption of  iron ,  calcium ,  magnesium , and  vitamin B 12 .<ref name="pmid20882439"> Ito T, Jensen RT (December 2010).  "Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium" .  Current Gastroenterology Reports .  12  (6):  448– 57.  doi : 10.1007/s11894-010-0141-0 .  PMC   2974811 .  PMID   20882439 .


Pseudopolyps  are projecting masses of  scar tissue  that develop from  granulation tissue  during the  healing  phase in repeated cycle of  ulceration  (especially in  inflammatory bowel disease ).  Inflammatory   tissue  without  malignant  potential, [ 1 ]  pseudopolyps may represent either regenerating mucosal islands between areas of ulceration, edematous polypoid tags or granulation tissue covered by epithelium. [ 2 ]  There are reported cases when localized giant pseudopolyposis resulted in intestinal obstruction. [ 3 ]


Residual mucosal islands between ulcerated and denuded areas of mucosa may have a polypoid appearance and are referred to as pseudopolyps. [ 4 ]  Polyposis syndromes, such as  familial adenomatous polyposis , could give rise to a similar appearance on  imaging , although the  clinical presentation  would differ from that of inflammatory pseudopolyposis. [ 5 ]


Numerous, confluent ulcerations with bulging of the edematous residual mucosa determine a  cobblestone  appearance at endoscopy. [ 6 ] [ 7 ]


A  rectal  or  anal dilator  is a medical device similar to a  speculum  designed to open and relax the  internal / external anal sphincter  and  rectum  in order to facilitate  medical inspection  or relieve  constipation . [ 1 ]  One early version of a rectal dilator was  Dr. Young's Ideal Rectal Dilators , invented in 1892. [ citation needed ]


Rectal dilators are also used as  sex toys . [ 2 ]


Rectal discharge  is intermittent or continuous expression of liquid from the anus ( per rectum ). Normal rectal mucus is needed for proper excretion of waste. Otherwise, this is closely related to types of  fecal incontinence  (e.g., fecal leakage) but the term rectal discharge does not necessarily imply degrees of incontinence. Types of fecal incontinence that produce a liquid leakage could be thought of as a type of rectal discharge.


Different types of discharge are described. Generally "rectal discharge" refers to either a mucous or  purulent  discharge, but, depending upon what definition of rectal discharge is used, the following could be included:


There are many different types of rectal discharge, but the most common presentation of a discharge is passage of mucus or pus wrapped around an otherwise normal bowel movement. [ 10 ]


Rectal discharge has many causes, and may present with other symptoms: [ 10 ] [ 11 ]


Pus  usually indicates  infection . Frequently medical sources do not differentiate between the two types of discharge, instead using the general term  mucopurulent discharge , which, strictly speaking, should only be used to refer to a discharge that contains both mucus and pus. Purulent discharges may be blood-streaked. [ citation needed ]


Mucus  coats the walls of the  colon  in health, functioning as a protective barrier and also to aid  peristalsis  by  lubrication  of  stool . Mucous discharges can be thought of in three broad categories:


A mucous rectal discharge may be blood-streaked. With some conditions, the blood can be homogenously mixed with the mucus, creating a pink goo. An example of this could be the so-called "red currant jelly" stools in  intussusception . This appearance refers to the mixture of sloughed  mucosa , mucus, and blood. [ 12 ]


Note : "mucus" is a noun, used to name the substance itself, and "mucous" is an adjective, used to describe a discharge. "Mucoid" is also an adjective and means mucus-like. "Mucinous" strictly speaking refers to something having a  mucin -like attribute, but it often is used interchangeably with the word "mucous" (as mucus usually contains a high percentage of mucin).


The differential diagnosis of rectal discharge is extensive,  but the general  etiological  themes are  infection  and  inflammation . [ 11 ]   Some lesions can cause a discharge by mechanically interfering with, or preventing the complete closure of, the  anal canal . This type of lesion may not cause discharge intrinsically, but instead, allow transit of liquid stool components and mucus.


Perianal  Crohn's disease  is associated with fistulizing, fissuring and perianal abscess formation. [ 18 ]


After  colostomy , the distal section of bowel continues to produce mucus despite fecal diversion, often resulting in mucinous discharge. [ 19 ]


Occasionally,  intestinal parasitic  infection can present with discharge, for example  whipworm . [ 20 ]


Several pathologies can present with perianal discharge. Although not exactly the same as rectal discharge, perianal discharge can be misinterpreted as such, given the anatomical proximity. [ citation needed ]


Fistulae  draining into the perianal region, as well as  pilonidal diseases , are the main entities that fall within this category. Perianal tumours can also discharge when they fungate or otherwise become cystic or necrotic. [ citation needed ]


Proctitis is inflammation of the lining of the rectum [ 21 ]  including the  distal  15 cm (6 in) of the rectum. [ citation needed ]


Proctitis  has many causes. Common infection causes include: sexual intercourse with someone who has a sexually transmitted disease (STD), infection from a foodborne illness, and strep throat (in children). [ 22 ]   Proctitis may also be caused by some types of inflammatory bowel disease, radiation therapy, injury to the rectum or anus, or some types of antibiotic. [ 22 ] [ clarification needed ] [ citation needed ]


Tuberculosis  proctitis can create a mucous discharge. [ 23 ]


Anal warts are irregular, verrucous lesions caused by  human papilloma virus . Anal warts are usually transmitted by unprotected,  anoreceptive intercourse .  Anal warts may be asymptomatic, [ 24 ]  or may cause rectal discharge, anal wetness,  rectal bleeding , and  pruritus ani . [ 14 ]  Lesions can also occur within the anal canal, where they are more likely to create symptoms. [ citation needed ]


The bacterium  Chlamydia trachomatis  can cause 2 conditions in humans; viz.  trachoma  and  lymphogranuloma venereum . Trachoma can cause an asymptomatic  proctitis , but the symptoms of lymphogranuloma venereum are usually more severe, including  pruritus ani , purulent rectal
discharge,  hematochezia   rectal pain  and  diarrhea  or  constipation . [ 14 ] [ 24 ]  Lymphogranuloma venereum can cause  fistulas ,  strictures  and  anorectal abscesses  if left untreated. Hence, it can be confused with Crohn's disease. [ 25 ] [ 26 ]


Rectal gonorrhea is caused by  Neisseria gonorrhoeae . [ 24 ]  The condition is usually asymptomatic, but symptoms can include rectal discharge (which can be creamy, purulent or bloody),  pruritus ani ,  tenesmus , and possibly  constipation . When symptomatic, these usually appear 5–7 days post-exposure. [ 14 ]  Discharge is the most common symptom, and it is usually a brownish mucopurulent consistency. [ 27 ]


Anorectal syphilis is caused by  Treponema pallidum  and is contracted through anoreceptive intercourse. Symptoms are usually minimal, but mucous discharge, bleeding, and  tenesmus  may be present. [ 27 ]


When the fecal stream is diverted as part of a  colostomy , a condition called  diversion colitis  may develop in the section of bowel that no longer is in contact with stool. The mucosal lining is nourished by short-chain fatty acids, which are produced as a result of bacterial fermentation in the gut. Long-term lack of exposure to these nutrients can cause inflammation of the colon (colitis). [ 28 ]  Symptoms include  rectal bleeding , mucous discharge,  tenesmus , and  abdominal pain . [ 27 ]


Anal carcinoma is much less common than  colorectal cancer . The most common form is  squamous cell carcinoma , followed by  adenocarcinoma  and  melanoma . [ 29 ]  SCC usually occurs in the anal canal, and more rarely on the anal margin. Anal margin SCC presents as a lesion with rolled, everted edges and central ulceration. [ 27 ]  Symptoms include a painful lump, bleeding,  pruritus ani ,  tenesmus , discharge or possibly  fecal incontinence . SSC in the anal canal most commonly causes bleeding, but may also cause anal pain, a lump,  pruritus ani , discharge,  tenesmus , change in bowel habits and  fecal incontinence . Because these symptoms are so unspecific, and because symptoms of anal carcinoma may not always be typical, this can lead to delays in diagnosis. [ 30 ]


Rare neoplasms at this site that can give rise to discharge include Paget's disease (which is possibly a type of adenocarcinoma) and verrucous carcinoma. [ 27 ]


Adenoma  is the most common colorectal  polyp . Adenomas are not malignant, but rarely  adenocarcinoma  can develop from them. Large adenomas can cause  rectal bleeding , mucus discharge,  tenesmus , and a sensation of urgency. Mucus production may be so great that it can cause  electrolyte  disturbances in the blood. [ 27 ]


Juvenile polyps  may cause rectal discharge.


The  Rome process and Rome criteria  are an international effort to create scientific data to help in the  diagnosis  and treatment of  functional gastrointestinal disorders , such as  irritable bowel syndrome ,  functional dyspepsia  and  rumination syndrome . The Rome diagnostic criteria are set forth by  Rome Foundation , a  not for profit  501(c)(3) organization based in  Raleigh, North Carolina , United States.


Several systematic approaches attempted to classify  functional gastrointestinal disorders  (FGIDs). As a result, there were several key events which ultimately led to the current Rome Classification. In 1962, Chaudhary and Truelove published their study of IBS patients in Oxford, England. This was the first attempt to classify the new field of functional gastrointestinal disorders. Much of what they reported has persisted to the present day. [ 1 ]


Subsequently, in 1978 came the "Manning Criteria" developed by  Kenneth Heaton  and colleagues in Bristol. This characterized IBS-D (IBS with predominant diarrhea), but importantly, a cluster of symptoms which were characteristic for this disorder. This ultimately became the basis for Rome's symptom-based criteria for IBS. [ 2 ]


From 1980 to 1994, there were several epidemiological and clinical studies evaluating symptom prevalence and frequency in healthy subjects and IBS patients. Thompson, Drossman, Talley, Whitehead, and Kruis. [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ]
In 1989, the first consensus-based diagnostic criteria for IBS were established. [ 3 ] [ 10 ]  The following year, a classification system for FGIDs was established. [ 3 ] [ 11 ]


From 1991 to 1993, several working teams (esophagus, gastroduodenal, bowel, biliary, anorectal) published symptom-based criteria and clinical features of the functional GI disorders within these anatomic domains in  Gastroenterology International . [ 3 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ]


In 1993, a validated questionnaire of all the diagnostic criteria was created and was then applied in a national survey, the US Householder Survey: the first national epidemiological database on the prevalence, demographic factors, and health care seeking features of people with FGIDs. [ 3 ] [ 18 ]


In 1994, FGIDs were categorized into anatomical domains and resulted in a book now recognized as Rome I –  The Functional Gastrointestinal Disorders: Diagnosis, Pathophysiology and Treatment – A Multinational Consensus . [ 3 ] [ 19 ]


The Rome criteria have been evolving from the first set of criteria issued in 1989 (The Rome Guidelines for IBS) through the Rome Classification System for functional gastrointestinal disorders (1990), or Rome-1, the Rome I Criteria for IBS (1992) and the functional gastrointestinal disorders (1994), the Rome II Criteria for IBS (1999) and the functional gastrointestinal disorders (1999) to the Rome III Criteria (2006). "Rome II" and "Rome III" incorporated  pediatric  criteria to the consensus.
The Rome IV update was published 10 years later in May 2016. [ 20 ]   This covers epidemiology, pathophysiology, psychosocial and clinical features, and diagnostic evaluation and treatment recommendations for 33 adult and 17 pediatric functional gastrointestinal disorders. [ 21 ]


The Rome criteria are achieved and finally issued through a  consensual process , using the  Delphi method  (or Delphi technique). The Rome Foundation process is an international effort to create scientific data to help in the diagnosis and treatment of functional gastrointestinal disorders, also known as disorders of gut-brain interaction. [ 22 ]   The Rome Diagnostic criteria are set forth by the Rome Foundation, an independent, not for profit 501(c)(3) organization. [ 22 ] [ 23 ]


The Rome Foundation, incorporated in 1996 and based in Raleigh, North Carolina, is an independent not for profit 501(c) 3 organization. The foundation provides support for activities which foster clinical research, data and educational information which aid in the diagnosis and treatment of functional gastrointestinal disorders. [ 22 ] [ 23 ] [ 24 ] [ 25 ]


Over the last 25 years, the Rome organization has sought to legitimize and update the knowledge of functional GI disorders. This has been accomplished by bringing together scientists and clinicians from around the world to classify and critically appraise the science of gastrointestinal function and dysfunction. This knowledge permits clinical scientists to make recommendations for diagnosis and treatment that can be applied in research and clinical practice. The mission is to improve the lives of people with these disorders. [ citation needed ]


The goals of the Rome Foundation are to promote global recognition and legitimization of FGIDs, advance the scientific understanding of their pathophysiology, optimize clinical management for these patients and develop and provide educational resources to accomplish these goals. [ 23 ]


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. [ 22 ]


A group of disorders classified by GI symptoms related to any combination of: [ 22 ]


In 1994, Rome I was published as The Functional Gastrointestinal Disorders:Diagnosis, Pathophysiology, and Treatment—A Multinational Consensus. [ 19 ]


By the mid-1990s, the concept of FGID classification and the use of diagnostic criteria was promoted due to the US Food and Drug Administration (FDA) recommended the use of the IBS criteria for selection into pharmaceutical studies, and the pharmaceutical companies took interest in supporting the efforts of the Rome Foundation to improve the understanding, diagnosis, and treatment of FGIDs and to also apply the use of these criteria in their pharmaceutical studies. In Rome II, the pediatric population of FGIDs was added.


After publication of Rome II, the number of studies published using the Rome criteria in clinical trials grew tremendously over the next 15 years. Rome III differed from Rome I and II by the use of more evidence-based rather than consensus-based data.


After publication of Rome III in 2006, the Rome Foundation was well recognized as the authoritative body developing diagnostic criteria for research and also for providing education about the FGIDs. Rome IV tried to address the limitations of a symptom-based criteria in several ways:


In Rome IV, the classification moved from a physiologically based classification to a symptom-based classification. The classifications were based upon organ regions (i.e. esophageal, gastroduodenal, bowel, biliary, anorectal).


The original Rome classification was first published in 1990 and has since been modified with each iteration to develop the subsequent classifications with Rome II, III and IV. Beginning with the original publication in 1990 and leading to Rome I, the classification moved from a physiologically based classification to a symptom-based classification with additional classifications based upon organ regions (i.e. esophageal, gastroduodenal, bowel, biliary, anorectal). [ 22 ]  The current Rome IV classification [ 22 ]  is the culmination of the evolution of a series of iterations (Rome I, [ 19 ]  Rome II, [ 27 ]  and Rome III [ 28 ] ) with its inception as Rome I. [ 19 ]


The Rome criteria are a set of criteria used by clinicians to classify a diagnosis of a patient with an FGID (disorder of gut-brain interaction). These Rome criteria are updated every 6–10 years. [ 24 ]


The current Rome IV classification, published in 2016, is as follows: [ 21 ]


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


As a non-profit organization the Rome Foundation has a number of industry sponsors who provide financial support. [ 29 ]


Rotaviruses  are the most common cause of  diarrhoeal disease  among infants and young children. [ 1 ]  Nearly every child in the world is infected with a rotavirus at least once by the age of five. [ 2 ]   Immunity  develops with each infection, so subsequent infections are less severe. Adults are rarely affected. [ 3 ]   Rotavirus  is a  genus  of  double-stranded RNA viruses  in the  family   Reoviridae . There are nine  species  of the genus, referred to as A, B, C, D, F, G, H, I and J.  Rotavirus A  is the most common species, and these rotaviruses cause more than 90% of rotavirus infections in humans. [ 4 ]


The virus is transmitted by the  faecal–oral route . It infects and damages the  cells  that line the  small intestine  and causes  gastroenteritis  (which is often called "stomach flu" despite having no relation to  influenza ). Although rotavirus was discovered in 1973 by  Ruth Bishop  and her colleagues by electron micrograph images [ 5 ]  and accounts for approximately one third of hospitalisations for severe diarrhoea in infants and children, [ 6 ]  its importance has historically been underestimated within the  public health  community, particularly in  developing countries . [ 7 ]  In addition to its impact on human health, rotavirus also infects other animals, and is a  pathogen  of livestock. [ 8 ]


Rotaviral enteritis is usually an easily managed disease of childhood, but among children under 5 years of age rotavirus caused an estimated 151,714 deaths from diarrhoea in 2019. [ 9 ]  In the United States, before initiation of the  rotavirus vaccination  programme in the 2000s, rotavirus caused about 2.7   million cases of severe gastroenteritis in children, almost 60,000 hospitalisations, and around 37 deaths each year. [ 10 ]  Following rotavirus vaccine introduction in the United States, hospitalisation rates have fallen significantly. [ 11 ] [ 12 ]  Public health campaigns to combat rotavirus focus on providing  oral rehydration therapy  for infected children and  vaccination  to prevent the disease. [ 13 ]  The incidence and severity of rotavirus infections has declined significantly in countries that have added rotavirus vaccine to their routine childhood  immunisation policies . [ 14 ] [ 15 ] [ 16 ]


There are nine species of rotavirus (sometimes informally called  groups ) referred to as A, B, C, D, F, G, H, I and J. [ 17 ] [ 18 ]  Humans are primarily infected by rotaviruses in the species  Rotavirus A . A–I species cause disease in other animals, [ 19 ]  species H in pigs, D, F and G in birds, I in cats and J in bats. [ 20 ] [ 21 ] [ 22 ] [ 23 ]


Within group A  rotaviruses there are different strains, called  serotypes . [ 24 ]  As with  influenza  virus, a dual classification system is used based on two proteins on the surface of the virus. The  glycoprotein  VP7 defines the G serotypes and the  protease -sensitive protein VP4 defines P serotypes. [ 25 ]  Because the two genes that determine G-types and P-types can be passed on separately to progeny viruses, different combinations are found. [ 25 ]  A whole genome genotyping system has been established for group A rotaviruses, which has been used to determine the origin of atypical strains. [ 26 ]  The prevalence of the individual G-types and P-types varies between, and within, countries and years. [ 27 ]  There are at least 36 G types and 51 P types [ 28 ]  but in infections of humans only a few combinations of G and P types predominate. They are G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8]. [ 29 ]


The  genome  of rotaviruses consists of 11 unique double helix molecules of  RNA  (dsRNA) which are 18,555 nucleotides in total. Each helix, or segment, is a  gene , numbered 1 to 11 by decreasing size. Each gene codes for one  protein , except genes 9, which codes for two. [ 30 ]  The RNA is surrounded by a three-layered  icosahedral  protein  capsid . Viral particles are up to 76.5   nm in diameter [ 31 ] [ 32 ]  and are not  enveloped . [ 33 ]


There are six viral proteins (VPs) that form the virus particle ( virion ). These  structural  proteins are called VP1, VP2, VP3, VP4, VP6 and VP7. In addition to the VPs, there are six  nonstructural  proteins  (NSPs), that are only produced in cells infected by rotavirus. These are called  NSP1 ,  NSP2 ,  NSP3 ,  NSP4 ,  NSP5  and  NSP6 . [ 19 ]


At least six of the twelve proteins  encoded  by the rotavirus genome bind  RNA . [ 35 ]  The role of these proteins in rotavirus replication is not entirely understood; their functions are thought to be related to RNA synthesis and packaging in the virion, mRNA transport to the site of genome replication, and  mRNA  translation and regulation of gene expression. [ 36 ]


VP1 is located in the core of the virus particle and is an  RNA-dependent RNA polymerase   enzyme . [ 37 ]  In an infected cell this enzyme produces mRNA transcripts for the synthesis of viral proteins and produces copies of the rotavirus genome RNA segments for newly produced virus particles. [ 38 ]


VP2 forms the core layer of the virion and binds the RNA genome. [ 39 ]


VP3 is part of the inner core of the virion and is an enzyme called  guanylyl transferase . This is a  capping enzyme  that catalyses the formation of the  5' cap  in the  post-transcriptional modification  of mRNA. [ 40 ]  The cap stabilises viral mRNA by protecting it from  nucleic acid  degrading enzymes called  nucleases . [ 41 ]


VP4 is on the surface of the virion that protrudes as a spike. [ 42 ]  It binds to molecules on the surface of cells called  receptors  and drives the entry of the virus into the cell. [ 43 ]  VP4 has to be modified by the  protease  enzyme  trypsin , which is found in the gut, into VP5* and VP8* before the virus is infectious. [ 44 ]  VP4 determines how  virulent  the virus is and it determines the P-type of the virus. [ 45 ]  In humans there is an association between the  blood group  ( Lewis antigen system ,  ABO blood group system  and  secretor status ) and susceptibility to infection. Non-secretors seem resistant to infection by types P[4] and P[8], indicating that blood group antigens are the receptors for these genotypes. [ 46 ]  This resistance is dependent on the rotavirus genotype. [ 47 ]


VP6 forms the bulk of the capsid. It is highly  antigenic  and can be used to identify rotavirus species. [ 48 ]  This protein is used in laboratory tests for rotavirus infections. [ 49 ]


VP7 is a  glycoprotein  that forms the outer surface of the virion. Apart from its structural functions, it determines the G-type of the strain and, along with VP4, is involved in  immunity  to infection. [ 31 ]


NSP1, the product of gene 5, is a  nonstructural  RNA-binding protein. [ 50 ]  NSP1 also blocks the  interferon  response, the part of the  innate immune system  that protects cells from viral infection. NSP1 causes the  proteosome  to degrade key signaling components required to stimulate production of interferon in an infected cell and to respond to interferon secreted by adjacent cells.


Targets for degradation include several  IRF  transcription factors required for interferon gene transcription. [ 51 ]


NSP2 is an  RNA-binding protein  that accumulates in cytoplasmic inclusions ( viroplasms ) and is required for genome replication. [ 52 ] [ 39 ]


NSP3 is bound to viral mRNAs in infected cells and it is responsible for the shutdown of cellular protein synthesis. [ 53 ]  NSP3 inactivates two translation initiation factors essential for synthesis of proteins from host mRNA.


First, NSP3 ejects  poly(A)-binding protein  (PABP) from the translation initiation factor  eIF4F .  PABP is required for efficient translation of transcripts with a 3'  poly(A) tail , which is found on most host cell transcripts. Second, NSP3 inactivates  eIF2  by stimulating its phosphorylation. [ 54 ]  Efficient translation of rotavirus mRNA, which lacks the 3' poly(A) tail, does not require either of these factors. [ 55 ]


NSP4 is a viral  enterotoxin  that induces diarrhoea and was the first viral enterotoxin discovered. [ 56 ]  It is a  viroporin  that elevates cytosolic Ca 2+  in mammalian cells. [ 57 ]


NSP5 is encoded by genome segment 11 of rotavirus A. In virus-infected cells NSP5 accumulates in the viroplasm. [ 58 ]


NSP6 is a nucleic acid binding protein [ 59 ]  and is encoded by gene 11 from an out-of-phase  open reading frame . [ 60 ]


This table is based on the  simian  rotavirus strain SA11. RNA-protein coding assignments differ in some strains.


The attachment of the virus to the host cell is initiated by VP4, which attaches to molecules, called  glycans , on the surface of the cell. [ 33 ]  The virus enters cells by  receptor mediated endocytosis  and form a  vesicle  known as an  endosome . Proteins in the third layer (VP7 and the VP4 spike) disrupt the membrane of the endosome, creating a difference in the  calcium  concentration. This causes the breakdown of VP7  trimers  into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP). [ 62 ]


The eleven dsRNA strands remain within the protection of the two protein shells and the viral  RNA-dependent RNA polymerase  creates mRNA transcripts of the double-stranded viral genome. By remaining in the core, the viral RNA evades innate host immune responses including  RNA interference  that are triggered by the presence of double-stranded RNA. [ 63 ]


During the infection, rotaviruses produce mRNA for both  protein biosynthesis  and gene replication. Most of the rotavirus proteins accumulate in viroplasm, where the RNA is replicated and the DLPs are assembled. In the viroplasm the positive sense viral RNAs that are used as templates for the synthesis of viral genomic dsRNA are protected from  siRNA -induced RNase degradation. [ 64 ]  Viroplasm is formed around the cell nucleus as early as two hours after virus infection, and consists of viral factories thought to be made by two viral nonstructural proteins: NSP5 and NSP2. Inhibition of NSP5 by RNA interference  in vitro  results in a sharp decrease in rotavirus replication. The DLPs migrate to the  endoplasmic reticulum  where they obtain their third, outer layer (formed by VP7 and VP4). The  progeny  viruses are released from the cell by  lysis . [ 44 ] [ 65 ] [ 66 ]


Rotaviruses are transmitted by the  faecal–oral route , via contact with contaminated hands, surfaces and objects, [ 67 ]  and possibly by the respiratory route. [ 68 ]  Viral diarrhoea is highly contagious. The faeces of an infected person can contain more than 10 trillion infectious particles per gram; [ 48 ]  fewer than 100 of these are required to transmit infection to another person. [ 3 ]


Rotaviruses are stable in the environment and have been found in  estuary  samples at levels up to 1–5 infectious particles per US   gallon. The viruses survive between 9 and 19 days. [ 69 ]  Sanitary measures adequate for eliminating  bacteria  and  parasites  seem to be ineffective in control of rotavirus, as the incidence of rotavirus infection in countries with high and low health standards is similar. [ 68 ]


Rotaviral enteritis is a mild to severe disease characterised by  nausea ,  vomiting , watery diarrhoea and low-grade  fever . Once a child is infected by the virus, there is an  incubation period  of about two days before symptoms appear. [ 70 ]  The period of illness is acute. Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea.  Dehydration  is more common in rotavirus infection than in most of those caused by bacterial pathogens, and is the most common cause of death related to rotavirus infection. [ 71 ]


Rotavirus infections can occur throughout life: the first usually  produces symptoms , but subsequent infections are typically mild or  asymptomatic , [ 72 ] [ 48 ]  as the immune system provides some protection. [ 73 ]  Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45 years of age. [ 74 ]  The most severe symptoms tend to occur in children six months to two years of age, the elderly, and those with  immunodeficiency . Due to immunity acquired in childhood, most adults are not susceptible to rotavirus; gastroenteritis in adults usually has a cause other than rotavirus, but asymptomatic infections in adults may maintain the transmission of infection in the community. [ 75 ]  There is some evidence to suggest blood group can impact on the susceptibility to infection by rotaviruses. [ 76 ]


Rotaviruses replicate mainly in the  gut , [ 77 ]  and infect enterocytes of the  villi  of the  small intestine , leading to structural and functional changes of the  epithelium . [ 78 ]  There is evidence in humans, and particularly in animal models of extraintestinal dissemination of infectious virus to other organs and macrophages. [ 79 ]


The diarrhoea is caused by multiple activities of the virus. [ 80 ]   Malabsorption  occurs because of the destruction of gut cells called  enterocytes . The  toxic  rotavirus protein  NSP4  induces age- and  calcium  ion-dependent  chloride  secretion, disrupts  SGLT1 (sodium/glucose cotransporter 2)   transporter -mediated reabsorption of water, apparently reduces activity of  brush-border membrane   disaccharidases , and activates the calcium ion-dependent  secretory   reflexes  of the  enteric nervous system . [ 56 ]  The elevated concentrations of calcium ions in the cytosol (which are required for the assembly of the progeny viruses) is achieved by NSP4 acting as a  viroporin . This increase in calcium ions leads to autophagy (self destruction) of the infected enterocytes. [ 81 ]


NSP4 is also secreted. This extracellular form, which is modified by  protease  enzymes in the gut, is an enterotoxin which acts on uninfected cells via  integrin  receptors, which in turn cause and increase in intracellular calcium ion concentrations, secretory diarrhoea and autophagy. [ 82 ]


The vomiting, which is a characteristic of rotaviral enteritis, is caused by the virus infecting the  enterochromaffin cells  on the lining of the digestive tract. The infection stimulates the production of 5' hydroxytryptamine ( serotonin ). This activates vagal afferent nerves, which in turn activates the cells of the brain stem that control the vomiting reflex. [ 83 ]


Healthy enterocytes secrete  lactase  into the small intestine; milk intolerance due to lactase deficiency is a symptom of rotavirus infection, [ 84 ]  which can persist for weeks. [ 85 ]  A recurrence of mild diarrhoea often follows the reintroduction of milk into the child's diet, due to bacterial fermentation of the  disaccharide   lactose  in the gut. [ 86 ]


Rotaviruses elicit both B and T cell immune responses. Antibodies to the rotavirus VP4 and VP7 proteins neutralise viral infectivity  in vitro  and  in vivo . [ 87 ]  Specific antibodies of the classes IgM, IgA and IgG are produced, which have been shown to protect against rotavirus infection by the passive transfer of the antibodies in other animals. [ 88 ]  Maternal trans-placental IgG might play a role in the protection neonates from rotavirus infections, but on the other hand might reduce vaccine efficacy. [ 89 ]


Following infection by rotaviruses there is a rapid innate immune response involving types I and III  interferons  and other  cytokines  (particularly Th1 and Th2) [ 90 ]  which inhibit the replication of the virus and recruit  macrophages  and  natural killer cells  to the rotavirus infected cells. [ 91 ]  The rotavirus dsRNA activates pattern recognition receptors such  toll-like receptors  that stimulate the production of interferons. [ 92 ]  The rotavirus protein NSP1 counteracts the effects of type 1 interferons by suppressing the activity of the interferon regulatory proteins IRF3, IRF5 and IRF7. [ 92 ]


The levels of IgG and IgA in the blood and IgA in the gut correlate with protection from infection. [ 93 ]  Rotavirus specific serum IgG and IgA at high  titres  (e.g. >1:200) have been claimed to be protective and there is a significant correlation between IgA titres and rotavirus vaccine efficacy. [ 94 ]


Diagnosis of infection with a rotavirus normally follows diagnosis of  gastroenteritis  as the cause of severe diarrhoea. Most children admitted to hospital with gastroenteritis are tested for rotavirus. [ 95 ] [ 96 ]


Specific  diagnosis  of infection with rotavirus is made by finding the virus in the child's  stool  by  enzyme immunoassay . There are several licensed test kits on the market which are sensitive, specific and detect all serotypes of rotavirus. [ 97 ]  Other methods, such as  electron microscopy  and  PCR  (polymerase chain reaction), are used in research laboratories. [ 98 ]  Reverse transcription-polymerase chain reaction ( RT-PCR ) can detect and identify all species and serotypes of human rotaviruses. [ 99 ]


Treatment of acute rotavirus infection is nonspecific and involves management of symptoms and, most importantly,  management of dehydration . [ 13 ]  If untreated, children can die from the resulting severe dehydration. [ 100 ]  Depending on the severity of diarrhoea, treatment consists of  oral rehydration therapy , during which the child is given extra water to drink that contains specific amounts of salt and sugar. [ 101 ]  In 2004, the World Health Organisation (WHO) and UNICEF recommended the use of low-osmolarity  oral rehydration solution  and  zinc  supplementation as a two-pronged treatment of acute diarrhoea. [ 102 ]  Some infections are serious enough to warrant hospitalisation where fluids are given by  intravenous therapy  or  nasogastric intubation , and the child's  electrolytes  and  blood sugar  are monitored. [ 95 ]  Rotavirus infections rarely cause other complications and for a well managed child the prognosis is excellent. [ 103 ]   Probiotics  have been shown to reduce the duration of rotavirus diarrhoea, [ 104 ]  and according to the European Society for Pediatric Gastroenterology "effective interventions include administration of specific probiotics such as  Lactobacillus rhamnosus  or  Saccharomyces boulardii ,  diosmectite  or  racecadotril ." [ 105 ]


Rotaviruses are highly contagious and cannot be treated with antibiotics or other drugs. Because improved  sanitation  does not decrease the prevalence of rotaviral disease, and the rate of hospitalisations remains high despite the use of oral rehydrating medicines, the primary public health intervention is vaccination. [ 2 ]  In 1998, a  rotavirus vaccine  was licensed for use in the United States.  Clinical trials  in the United States, Finland, and Venezuela had found it to be 80–100% effective at preventing severe diarrhoea caused by  rotavirus A , and researchers had detected no  statistically significant  serious  adverse effects . [ 106 ] [ 107 ]  The manufacturer, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for  intussusception , a type of  bowel obstruction , in one of every 12,000 vaccinated infants. [ 108 ]  The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine. [ 109 ]


In 2006, two new vaccines against  rotavirus A  infection were shown to be safe and effective in children, [ 110 ]  and in 2009, the WHO recommended that rotavirus vaccine be included in all national immunisation programmes. [ 111 ]


The incidence and severity of rotavirus infections has declined significantly in countries that have acted on this recommendation. [ 14 ] [ 15 ] [ 16 ]  A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunisation programs found that rotavirus vaccines have reduced rotavirus hospitalisations by 49–92% and all cause diarrhoea hospitalisations by 17–55%. [ 112 ]  In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, diarrhoeal disease death rates dropped during the 2009 rotavirus season by more than 65 percent among children age two and under. [ 113 ]  In Nicaragua, which in 2006 became the first developing country to introduce a rotavirus vaccine, severe rotavirus infections were reduced by 40 percent and emergency room visits by a half. [ 114 ]  In the United States, rotavirus vaccination since 2006 has led to drops in rotavirus-related hospitalisations by as much as 86 percent. [ 115 ]  The vaccines may also have prevented illness in non-vaccinated children by limiting the number of circulating infections. [ 115 ] [ 116 ]  In developing countries in Africa and Asia, where the majority of rotavirus deaths occur, a large number of safety and efficacy trials as well as recent post-introduction impact and effectiveness studies of Rotarix and RotaTeq have found that vaccines dramatically reduced severe disease among infants. [ 16 ] [ 117 ] [ 118 ] [ 119 ]  In September 2013, the vaccine was offered to all children in the UK, aged between two and three months. [ 120 ]  A 2022 study found that the number of rotavirus cases in infants in England under one year of age was reduced by 77–88%. In all age groups, the number of laboratory-confirmed rotavirus infections was reduced by 69–83%. [ 121 ]   In Europe, hospitalisation rates following infection by rotaviruses have decreased by 65% to 84% following the introduction of the vaccine. [ 122 ]  Globally, vaccination has reduced hospital admissions and emergency department visits by a median of 67%. [ 123 ]


Rotavirus vaccines are licensed in over 100 countries, and more than 80 countries have introduced routine rotavirus vaccination, almost half with the support of the  GAVI  vaccine alliance. [ 124 ]  To make rotavirus vaccines available, accessible, and affordable in all countries—particularly low- and middle-income countries in Africa and Asia where the majority of rotavirus deaths occur,  PATH  (formerly Program for Appropriate Technology in Health), the WHO, the U.S.  Centers for Disease Control and Prevention , and GAVI have partnered with research institutions and governments to generate and disseminate evidence, lower prices, and accelerate introduction. [ 125 ]


The vaccine may prevent  type 1 diabetes . [ 126 ] [ 127 ]


Rotavirus A , which accounts for more than 90% of rotavirus gastroenteritis in humans, [ 4 ]  is  endemic  worldwide. Each year rotaviruses cause millions of cases of diarrhoea in developing countries, almost 2   million of which result in hospitalisation. [ 7 ]  In 2019, an estimated 151,714 children younger than five died from rotavirus infections, 90 percent of whom were in developing countries. [ 9 ]  Almost every child has been infected with rotaviruses by age five. [ 2 ] [ 128 ]  Rotaviruses are the leading single cause of severe diarrhoea among infants and children, are responsible for about a third of the cases requiring hospitalisation, [ 11 ]  and cause 37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than five. [ 129 ]  Boys are twice as likely as girls to be admitted to hospital for rotavirus infections. [ 130 ] [ 131 ]  In the pre-vaccination era, rotavirus infections occurred primarily during cool, dry seasons. [ 132 ] [ 133 ]  The number attributable to food contamination is unknown. [ 134 ]


Outbreaks of  rotavirus A  diarrhoea are common among hospitalised infants, young children attending day care centres, and elderly people in nursing homes. [ 75 ] [ 135 ]  An outbreak caused by contaminated municipal water occurred in Colorado in 1981. [ 136 ]  During 2005, the largest recorded epidemic of diarrhoea occurred in Nicaragua. This unusually large and severe outbreak was associated with mutations in the  rotavirus A  genome, possibly helping the virus escape the prevalent immunity in the population. [ 137 ]  A similar large outbreak occurred in Brazil in 1977. [ 138 ]


Rotavirus B , also called adult diarrhoea rotavirus or ADRV, has caused major epidemics of severe diarrhoea affecting thousands of people of all ages in China. These epidemics occurred as a result of sewage contamination of drinking water. [ 139 ] [ 140 ]   Rotavirus B  infections also occurred in India in 1998; the causative strain was named CAL. Unlike ADRV, the CAL strain is endemic. [ 141 ] [ 142 ]  To date, epidemics caused by  rotavirus B  have been confined to  mainland China , and surveys indicate a lack of immunity to this species in the United States. [ 143 ]   Rotavirus C  has been associated with rare and sporadic cases of diarrhoea in children, and small outbreaks have occurred in families. [ 144 ]


Rotaviruses infect the young of many species of animals and they are a major cause of diarrhoea in wild and reared animals worldwide. [ 8 ]  As a pathogen of livestock, notably in young calves and piglets, rotaviruses cause  economic loss to farmers because of costs of treatment associated with high morbidity and mortality rates. [ 147 ]  These rotaviruses are a potential reservoir for genetic exchange with human rotaviruses. [ 147 ]  There is evidence that animal rotaviruses can infect humans, either by direct transmission of the virus or by contributing one or several RNA segments to  reassortants  with human strains. [ 148 ] [ 149 ] [ 150 ]


In 1943, Jacob Light and Horace Hodes proved that a filterable agent in the faeces of children with infectious diarrhoea also caused scours (livestock diarrhoea) in cattle. [ 151 ]  Three decades later, preserved samples of the agent were shown to be rotavirus. [ 152 ]  In the intervening years, a virus in mice [ 153 ]  was shown to be related to the virus causing scours. [ 154 ]  In 1973,  Ruth Bishop  and colleagues described related viruses found in children with gastroenteritis. [ 5 ]


In 1974,  Thomas Henry Flewett  suggested the name  rotavirus  after observing that, when viewed through an  electron microscope , a rotavirus particle looks like a wheel ( rota  in Latin) [ 155 ] [ 156 ]  the name was officially recognised by the  International Committee on Taxonomy of Viruses  four years later. [ 157 ]  In 1976, related viruses were described in several other species of animals. [ 154 ]  These viruses, all causing acute gastroenteritis, were recognised as a collective pathogen affecting humans and other animals worldwide. [ 155 ]  Rotavirus serotypes were first described in 1980, [ 158 ]  and in the following year, rotaviruses from humans were first grown in  cell cultures  derived from monkey kidneys, by adding  trypsin  (an enzyme found in the  duodenum  of  mammals  and now known to be essential for rotavirus to replicate) to the culture medium. [ 159 ]  The ability to grow rotaviruses in culture accelerated the pace of research, and by the mid-1980s the first candidate vaccines were being evaluated. [ 160 ]


The  rotavirus vaccine  is a  vaccine  used to protect against  rotavirus  infections, which are the leading cause of severe  diarrhea  among young children. [ 6 ]  The vaccines prevent 15–34% of severe diarrhea in the  developing world  and 37–96% of the risk of death among young children due to severe diarrhea. [ 6 ]  Immunizing babies decreases rates of disease among older people and those who have not been immunized. [ 7 ]


The  World Health Organization  (WHO) recommends that rotavirus vaccine be included in national  routine vaccinations  programs, especially in areas where the disease is common. [ 6 ]  This should be done along with promoting  breastfeeding , handwashing, clean water, and good sanitation. [ 6 ]  It is given  by mouth  and requires two or three doses. [ 6 ]  The vaccines are safe. [ 6 ]  This includes their use in people with  HIV/AIDS . [ 6 ]  The vaccines are made from  weakened rotavirus . [ 6 ]


The vaccine first became available in the United States in 2006. [ 8 ]  It is on the  World Health Organization's List of Essential Medicines . [ 9 ]  The vaccine is available in many countries. [ 6 ]


Safety and efficacy trials in Africa and Asia found that the vaccines dramatically reduced severe disease among infants in developing countries, where a majority of rotavirus-related deaths occur. [ 10 ] [ 11 ]  A 2021  Cochrane  systematic review concluded that Rotavac, Rotateq, and Rotarix vaccines are safe and are effective at preventing diarrhea that is related to a rotavirus infection. [ 12 ]


Rotavirus vaccines are licensed in more than 100 countries, and more than 80 countries have introduced routine rotavirus vaccination. [ 13 ]  The incidence and severity of rotavirus infections has declined significantly in countries that have acted on the recommendation to introduce the rotavirus vaccine. [ 14 ]  In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, the diarrheal disease death rates from rotavirus dropped by more than 65% among children age two and under during the 2009 rotavirus season. [ 15 ]  In Nicaragua, which in 2006 became the first developing country to introduce the rotavirus vaccine, investigators recorded a substantial impact, with rotavirus vaccine preventing 60% of cases against severe rotavirus and cutting emergency room visits in half. [ 16 ]  In the United States, vaccination has reduced rotavirus-related hospitalizations by as much as 86% since 2006. In April 2016, the World Health Organization released statistics for the period of 2000–2013, which showed developing countries that have introduced rotavirus vaccines experienced significant decreases in deaths and hospitalizations from rotavirus diarrhea after introduction. [ 17 ] [ 11 ]


Additionally, the vaccines may also prevent illness in non-vaccinated children by limiting exposure through the number of circulating infections. [ 7 ]  A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunization programs found that rotavirus vaccines have reduced rotavirus hospitalizations by 49–92% and all-cause diarrhea hospitalizations by 17–55%. [ 18 ]


The World Health Organization recommends the first dose of vaccine be given right after six weeks of age. [ 6 ]


Rotarix is a  monovalent , human, live attenuated rotavirus vaccine containing one rotavirus strain of G1P[8] specificity.
Rotarix is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9) when administered as a 2-dose series in infants and children. [ 19 ]  It was approved in the European Union in 2006, and by the US FDA in April 2008. [ 20 ] [ 21 ]  It is taken  by mouth . [ 22 ] [ 23 ]


Rotateq is a live, oral  pentavalent vaccine  that contains five rotavirus strains produced by  reassortment . [ medical citation needed ]  The rotavirus   A parent strains of the reassortants were isolated from human and bovine hosts. [ medical citation needed ]  Four reassortant rotaviruses express one of the outer capsid, VP7, proteins (serotypes G1, G2, G3, or G4) from the human rotavirus parent strain and the attachment protein VP4 (type P7) from the bovine rotavirus parent strain. [ medical citation needed ]  The fifth reassortant virus expresses the attachment protein VP4, (type P1A), from the human rotavirus parent strain and the outer capsid protein VP7 (serotype G6) from the bovine rotavirus parent strain. [ medical citation needed ]  In February 2006, the US  Food and Drug Administration  (FDA) approved Rotateq for use in the United States. [ 24 ] [ 25 ]  In August 2006,  Health Canada  approved Rotateq for use in Canada. [ 26 ]  Merck worked with a range of partners including governmental and non-governmental organisations to develop and implement mechanisms for providing access to this vaccine in the developing world, [ 27 ]  an effort which was slated to come to an end in 2020. [ 28 ]


Rotavac was licensed for use in India in 2014 and is manufactured by  Bharat Biotech International Limited . It is a live attenuated, monovalent vaccine containing a G9P[11] human strain isolated from an Indian child. [ 29 ]  It is given by mouth in a three-dose series, four weeks apart, beginning at six weeks of age up until eight months of age. [ 30 ]


Rotavin-M1 was licensed for use in Vietnam in 2007 and is manufactured by the Center for Research and Production of Vaccines. The vaccine contains a G1P[8] human rotavirus strain. [ 31 ]


The Lanzhou lamb rotavirus vaccine was licensed for use in China in 2000 and is manufactured by the Lanzhou Institute of Biological Products. It contains a G10P[12] lamb rotavirus strain. [ 31 ]


Rotasiil is a  lyophilized  pentavalent vaccine licensed for use in India in 2018. It contains human bovine reassortant strains of rotavirus serotypes G1, G2, G3, G4, and G9. This is the world's first thermostable vaccine which can be stored without refrigeration at or below 25 °C. Rotasiil is manufactured by the  Serum Institute of India . [ 32 ] [ 33 ]


In 1998, a rotavirus vaccine (RotaShield, by  Wyeth ) was licensed for use in the United States. Clinical trials in the United States,  Finland , and  Venezuela  had found it to be 80 to 100% effective at preventing severe diarrhea caused by rotavirus   A, and researchers had detected no statistically significant serious adverse effects. However post-licensure studies conducted in the United States by  Trudy Murphy  and her colleagues at the Centers For Disease Control and Prevention (CDC) and Kramarz et al., found that Infants who received the vaccine were 30 times more likely to develop a severe form of bowel obstruction, called intussusception, during 3 to 7 days after the first dose than unvaccinated infants. [ 34 ] [ 35 ]  The excess risk was estimated between one case in 5,000 to 10,000 vaccinees. Based on these data, the Advisory Committee on Immunization Practices (ACIP) withdrew its recommendation to use the vaccine, [ 36 ]  and the manufacturer of the vaccine withdrew it from the market in 1999. There then followed eight years of delay until rival manufacturers were able to introduce new vaccines that were shown to be more safe and effective in children: Rotarix by  GlaxoSmithKline [ 19 ]  and Rotateq by  Merck . [ 37 ]  Both are taken orally and contain disabled live virus. [ 8 ]


The World Health Organization recommends that rotavirus vaccine be included in all national immunization schedules because the risk of intussusception following rotavirus vaccination remains very low compared with the benefits of preventing the impact of severe and deadly diarrhoea. [ 38 ]


A 2009 review estimated that vaccination against rotavirus would prevent about 45% of deaths due to rotavirus gastroenteritis, or about 228,000 deaths annually worldwide. At US$5 per dose, the estimated cost per life saved was $3,015, $9,951, and $11,296 in low-, lower-middle-, and upper-middle-income countries, respectively. [ 39 ]


More than 80 countries have introduced routine rotavirus vaccination, almost half with the support of  Gavi, the Vaccine Alliance . [ 31 ]


In March 2010, the detection of DNA from  porcine circovirus  types 1 and 2 within Rotateq and Rotarix prompted the FDA to suspend the use of rotavirus vaccines while conducting an investigation the finding of DNA from porcine circovirus-1 (PCV1) in the vaccine in collaboration with the 12 members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC). [ 40 ]  On 6 May 2010, the FDA announced its decision to revoke the suspension, stating that porcine circovirus types 1 and 2 pose no safety risks in humans and concluded that health risks involved did not offset the benefits of the vaccination. [ 40 ]  In May 2010 the suspension of the Rotarix vaccine was lifted. [ 41 ]


Doctors Without Borders  (MSF) developed a heat-stable version named BRV-PV. Phase 3 of the clinical trials was completed in Niger on 31 December 2020. [ 42 ] [ 43 ]


The vaccine has been associated with lower rates of  type 1 diabetes . [ 44 ] [ 45 ]


SeHCAT  ( 23-seleno-25-homotaurocholic acid ,  selenium homocholic acid taurine , or  tauroselcholic acid ) is a drug used in a clinical test to diagnose  bile acid malabsorption . [ 1 ]


SeHCAT is a taurine-conjugated  bile acid   analog  which was synthesized for use as a  radiopharmaceutical  to investigate  in vivo  the  enterohepatic circulation  of  bile salts . [ 2 ]  By incorporating the gamma-emitter  75 Se into the SeHCAT molecule, the retention in the body or the loss of this compound into the feces could be studied easily using a standard gamma camera, available in most clinical  nuclear medicine  departments. [ citation needed ]


SeHCAT has been shown to be absorbed from the gut and excreted into the bile at the same rate as  cholic acid , one of the major natural bile acids in humans. It undergoes secretion into the biliary tree, gallbladder and intestine in response to food, and is reabsorbed efficiently in the ileum, with kinetics similar to natural bile acids. [ 2 ] [ 3 ]  It was soon shown to be the most convenient and accurate method available to assess and measure  bile acid  turnover in the intestine. [ 4 ]  SeHCAT testing was commercially developed by Amersham International Ltd ( Amersham plc  is now part of  GE Healthcare  Medical Diagnostics division) for clinical use to investigate  malabsorption  in patients with  diarrhea . This test has replaced  14 C-labeled glycocholic acid (or taurocholic acid) breath tests and fecal bile acid measurements, which now have no place in the routine clinical investigation of  malabsorption . [ citation needed ]


A capsule containing radiolabelled  75 SeHCAT (with 370 kBq of Selenium-75 and less than 0.1 mg SeHCAT) is taken orally with water, to ensure passage of the capsule into the gastrointestinal tract. The physical half life of  75 Se is approximately 118 days; activity is adjusted to a standard reference date. [ citation needed ]


Patients may be given instructions to fast prior to capsule administration; there is significant variation in clinical practice in this regard. [ 5 ]  The effective dose of radiation for an adult given 370 kBq of SeHCAT is 0.26 mSv. [ 6 ]  (For comparison, the radiation exposure from an abdominal  CT scan  is quoted at 5.3 mSv and annual background exposure in the UK 1-3 mSv. [ 7 ] ) Measurements were originally performed with a whole-body counter but are usually performed now with an uncollimated gamma camera.  The patient is scanned supine or prone with anterior and posterior acquisition from head to thigh 1 to 3 hours after taking the capsule. Scanning is repeated after 7 days. Background values are subtracted and care must be taken to avoid external sources of radiation in a nuclear medicine department.


From these measurements, the percent retention of SeHCAT at 7 days is calculated.  A 7-day SeHCAT retention value greater than 15% is considered to be normal, with values less than 15% signifying excessive bile acid loss, as found in  bile acid malabsorption .


With more frequent measurements, it is possible to calculate SeHCAT retention whole-body half-life; this is not routinely measured in a clinical setting. A half-life of greater than 2.8 days has been quoted as normal. [ 8 ]


The SeHCAT test is used to investigate patients with suspected  bile acid malabsorption , who usually experience  chronic diarrhea , often passing watery feces 5 to 10 times each day. When ileum has been removed following surgery, or is inflamed in  Crohn's disease , the 7-day SeHCAT retention usually is abnormal, and most of these patients will benefit from treatment with  bile acid sequestrants . [ 9 ] [ 10 ]  The  enterohepatic circulation  of bile acids is reduced in these patients with ileal abnormalities and, as the normal bile acid retention exceeds 95%, only a small degree of change is needed.  Bile acid malabsorption  can also be secondary to  cholecystectomy ,  vagotomy  and other disorders affecting intestinal motility or digestion such as radiation enteritis,  celiac disease , and  small intestinal bacterial overgrowth . [ citation needed ]


A similar picture of  chronic diarrhea , an abnormal SeHCAT retention and a response to  bile acid sequestrants , in the absence of other disorders of the intestine, is characteristic of idiopathic  bile acid malabsorption  – also called  primary bile acid diarrhea . These patients are frequently misdiagnosed as having the  irritable bowel syndrome , as clinicians fail to recognize the condition, do not think of performing a SeHCAT test, or do not have it available. [ 11 ]


There have been at least 18 studies of the use of SeHCAT testing in diarrhea-predominant  irritable bowel syndrome  patients. When these data were combined, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a  bile acid sequestrant . [ 12 ]


A  self-expandable metallic stent  (or  SEMS ) is a metallic tube, or  stent  that holds open a structure in the  gastrointestinal tract  to allow the passage of food,  chyme ,  stool , or other secretions related to  digestion . Surgeons insert SEMS by  endoscopy , inserting a  fibre optic  camera—either through the  mouth  or  colon —to reach an area of narrowing. As such, it is termed an  endoprosthesis . SEMS can also be inserted using  fluoroscopy  where the surgeon uses an X-ray image to guide insertion, or as an adjunct to endoscopy.


The vast majority of SEMS are used to alleviate symptoms caused by  cancers  of the gastrointestinal tract that obstruct the interior of the tube-like (or luminal) structures of the bowel — namely the  esophagus ,  duodenum ,  common bile duct  and colon. SEMS are designed to be permanent and, as a result, are often used when the cancer is at an advanced stage and cannot be removed by surgery.


Self-expandable metallic stents are cylindrical in shape, and are devised in a number of diameters and lengths to suit the application in question. [ 1 ]  They typically consist of cross-hatched, braided or interconnecting rows of metal that are assembled into a tube-like structure. SEMS, when unexpanded, are small enough to fit through the channel of an  endoscope , which is meant for delivery of devices for therapeutic endoscopy. They expand through a deployment device placed at the end of the SEMS, and are held in place against the wall of the luminal surface by friction. [ 2 ]


SEMS may be coated with chemicals designed to prevent tumour ingrowth; these are termed "covered" stents.  Nitinol [ 3 ]  (a  shape memory   nickel - titanium  alloy),  polyurethane , [ 4 ]  and  polyethylene [ 5 ]  are typically used as coatings for SEMS. Covered stents carry the advantage of preventing tumours from growing into the stent, although they run the risk of increased migration after deployment. [ 6 ]


A plastic self-expanding stent (Polyflex,  Boston Scientific ) has also been developed for similar applications. It confers an additional advantage as it is designed to be removable, and may have a less traumatic insertion than metal stents. The Polyflex stent has shown benefit in palliation of esophageal malignancies. [ 7 ]


The primary application of SEMS is in the  palliation  of tumours that obstruct the gastrointestinal tract. When they expand within the lumen, they are able to hold open the structure and allow passage of material, such as food, stool, or other secretions. The usual applications are for cancers of the  esophagus ,  pancreas ,  bile ducts  and  colon  that are not amenable to surgical therapy. SEMS are used to treat additional complications of cancer, such as  tracheoesophageal fistulas  from esophageal cancer, [ 8 ]  and  gastric outlet obstruction  from  stomach , duodenal, or pancreatic cancer. [ 9 ]


SEMS and self-expanding plastic stents have also been used for non-malignant conditions that cause narrowing or leaks of the esophagus or colon. These include  peptic strictures  caused by esophageal reflux [ 10 ]  and perforations of the esophagus. [ 11 ]  SEMS may also be placed in tandem fashion to treat ingrowth or overgrowth tumours, and fractures or migration of other SEMS. For the latter, the second SEMS in usually deployed within the lumen of the first. [ 12 ]


SEMS are also sometimes used in the  vascular system , usually in the  aorta  and  peripheral vascular system . In the past they have been used for  saphenous vein graft  and native  coronary artery   percutaneous coronary interventions . [ citation needed ]


Self-expandable metallic stents are typically inserted at the time of  endoscopy , usually with assistance with  fluoroscopy  or  x-ray  images taken to guide placement. Prior to the development of SEMS small enough to pass through the channel of the endoscopy, SEMS were deployed using fluoroscopy alone. [ 13 ]


Esophageal SEMS are placed after a gastroscopy is performed to identify the area of narrowing. The area may need to be dilated to allow the gastroscope to pass. [ 14 ]  The tumour is usually better seen with the direct vision of endoscopy than on a fluoroscopic image. As a result, radio-opaque markers are usually placed on the surface of the patient to mark the area of narrowing on fluoroscopy. The SEMS is placed through the channel of the endoscope into the esophagus over a guidewire, marked on fluoroscopy, and mechanically deployed (using a device that sits outside of the endoscope) such that it expands when in position.  Hypaque  or other water-soluble dye may be placed through the passage to ensure patency of the stent on fluoroscopy. [ 15 ]  Enteric and colonic SEMS are inserted in a similar fashion, but in the duodenum and colon respectively. [ 16 ]


Biliary SEMS are used to palliatively treat tumours of the pancreas or bile duct that obstruct the  common bile duct . They are inserted at the time of  ERCP , a procedure that uses endoscopy and fluoroscopy to access the common bile duct. The bile duct is  cannulated  with the assistance of a guidewire and the  sphincter of Oddi  that is located at its base is typically cut. A wire is kept in the bile duct, and the SEMS is deployed over the wire in a similar fashion as  esophageal stents . The location of the SEMS is confirmed by fluoroscopy. [ 17 ]


The complications of SEMS are related to a number of factors. The first is that the endoscopic procedure used to insert a SEMS involves the use of  sedative  medications, which may lead to oversedation,  aspiration , or  drug reaction . SEMS also expand and can lead to  perforation  of the bowel or compression of structures adjacent to the bowel. [ 18 ]


Long-term complications of SEMS may be related to the underlying tumour being treated: the tumour may grow into the stent wall (tumour ingrowth) or over the end of the stent (tumour overgrowth), leading to obstruction. These complications may be limited by the use of coated stents. [ 6 ] [ 19 ]  Tumour ingrowth or overgrowth can be additionally palliated by the placement of a second stent through the lumen of the first, [ 6 ]  through  electrocautery  or  argon plasma coagulation  of the tumour tissue in the stent, [ 6 ]  or through the use of  photodynamic therapy . [ 20 ]


Over time, SEMS may also migrate to a different position that does not help with treatment of the obstructed area. [ 6 ]  This may be treated with placement of a second SEMS, or endoscopic attempts to reposition or remove the first. [ 21 ]  Rarely, SEMS may fracture [ 12 ]  or  intussescept  after endoscopic intervention. [ 22 ]


A  Sengstaken–Blakemore tube  is a  medical device  inserted through the nose or mouth and used occasionally in the management of  upper gastrointestinal hemorrhage  due to  esophageal varices  (distended and fragile veins in the esophageal wall, usually a result of  cirrhosis ). The use of the tube was originally described in 1950, [ 1 ]  although similar approaches to bleeding varices were described by Westphal in 1930. [ 2 ]  With the advent of  modern endoscopic techniques  which can rapidly and definitively control variceal bleeding, Sengstaken–Blakemore tubes are rarely used at present. [ 3 ]


The device consists of a flexible plastic tube containing several internal channels and two inflatable balloons. Apart from the balloons, the tube has an opening at the bottom (gastric tip) of the device. More modern models also have an opening near the upper esophagus; such devices are properly termed  Minnesota tubes . [ 3 ] [ 4 ]  The tube is passed down into the  esophagus  and the gastric balloon is inflated inside the stomach. A traction of 1 kg is applied to the tube so that the gastric balloon will compress the gastroesophageal junction and reduce the blood flow to esophageal varices. If the use of traction alone cannot stop the bleeding, the esophageal balloon is also inflated to help stop the bleeding. The esophageal balloon should not remain inflated for more than six hours, to avoid necrosis. The gastric lumen is used to aspirate stomach contents. [ citation needed ]


Generally, Sengstaken–Blakemore tubes and Minnesota tubes are used only in emergencies where bleeding from presumed varices is impossible to control with medication alone. The tube may be difficult to position, particularly in an unwell patient, and may inadvertently be inserted in the  trachea , hence endotracheal intubation before the procedure is strongly advised to secure the airway. The tube is often kept in the refrigerator in the hospital's emergency department, intensive care unit and gastroenterology ward. It is a temporary measure: ulceration and rupture of the esophagus and stomach are recognized complications. [ 4 ] [ 5 ]


A related device with a larger gastric balloon capacity (about 500 ml), the  Linton–Nachlas tube , is used for bleeding  gastric varices . It does not have an esophageal balloon.


It is named after Robert William Sengstaken Sr. (1923–1978), an American neurosurgeon, and Arthur Blakemore (1897–1970), an American vascular surgeon. They conceptualized and invented the tube in the early 1950s.


A  sentinel loop  is a  sign  seen on a radiograph that indicates localized  ileus  from nearby inflammation. [ 1 ]  Simply put, it is the dilation of a segment of  small intestine  to be differentiated from  colonic cutoff sign  which is a dilation of a segment of large bowel. [ citation needed ]


An isolated distended loop of bowel is seen near the site of injured viscus or inflamed organ. This loop is called a "sentinel loop." It arises from the body's efforts to localize traumatic or inflammatory lesions. The local distention of that intestinal loop is due to local paralysis and accumulation of gas in the intestinal loop. In acute  pancreatitis , the sentinel loop is usually seen in the left  hypochondrium , while in acute  cholecystitis , it is seen in the right hypochondrium. In acute  appendicitis , the sentinel loop is seen in the  right lower quadrant . [ 2 ]


Sleisenger and Fordtran's Gastrointestinal and Liver Disease  is a textbook on  hepatology  and  gastroenterology  for medical students, internists, and surgeons. [ 1 ]  First published in 1978, it has undergone many revisions to reflect the rapid advances in internal medicine and is currently in its 11th edition. It has been described as "a comprehensive and authoritative textbook of gastrointestinal diseases", [ 2 ]  the "standard bearer in gastrointestinal textbooks", [ 3 ]  and "the dominant textbook of gastroenterology". [ 4 ]


In  anatomy , a  stoma  ( pl. :  stomata   / ˈ s t oʊ m ə t ə /  or  stomas ) is any opening in the body. For example, a  mouth , a  nose , and an  anus  are natural stomata. Any hollow  organ  can be manipulated into an artificial stoma as necessary.  This includes the  esophagus ,  stomach ,  duodenum ,  ileum ,  colon ,  pleural cavity ,  ureters ,  urinary bladder , and  renal pelvis . Such a stoma may be permanent or temporary. [ citation needed ]


Surgical procedures that involve the creation of an artificial stoma have names that typically end with the suffix "-ostomy", and the same names are also often used to refer to the stoma thus created. For example, the word " colostomy " often refers either to an artificial anus or the procedure that creates one. Accordingly, it is not unusual for a stoma to be called an  ostomy  (plural  ostomies ), as is the norm in  wound, ostomy, and continence nursing .


Stomata are created in particular in surgical procedures involving the  gastrointestinal tract  (GIT) or gastrointestinal system (GIS). The GIT begins at the mouth or oral cavity and continues until its termination, which is the anus. Examples of gastrointestinal stomata include: [ citation needed ]


One well-known form of an artificial stoma is a  colostomy , which is a surgically created opening in the  large intestine  that allows the removal of  feces  out of the body, bypassing the  rectum , to drain into a  pouch  or other collection device. This  surgical  procedure is invoked usually as a result of and solution to disease in the GIT. The procedure involves bisecting this tube, usually between the later stage of the small intestine ( ileum ) and the large intestine or  colon , hence colostomy, and exiting it from the body in the abdominal region. The point of exiting is what is known as the stoma.


For greatest success and to minimize negative effects, it is preferable to perform this procedure as low down in the tract as possible, as this allows the maximal amount of natural  digestion  to occur before eliminating  fecal  matter from the body. The stoma is usually covered with a removable pouching system (adhesive or mechanical) that collects and contains the output for later disposal. Modern  pouching systems  enable most individuals to resume normal activities and lifestyles after surgery, often with no outward physical evidence of the stoma or its pouching system.


When planning the position of the stoma, a stoma nurse should bear in mind the height of the person's waist and beltline so that clothes can fit as before. Also a peri-stomal hernia belt worn from the start can help prevent the stoma from developing a serious hernia problem.


The historical practice of  trepanation  was also a type of stoma.


Stomachic  is a historic term for a medicine that serves to  tone  the  stomach , improving its function and increase appetite.  While many  herbal remedies  claim stomachic effects, modern  pharmacology  does not have an equivalent term for this type of action.


Herbs with putative stomachic effects include: [ citation needed ]


The purported stomachic  mechanism of action  of these substances is to stimulate the appetite by increasing the gastric secretions of the stomach; however, the actual therapeutic value of some of these compounds is dubious.  Some other important agents used are:


In  fecal incontinence  (FI), surgery may be carried out if conservative measures alone are not sufficient to control symptoms. There are many surgical options described for FI, and they can be considered in 4 general groups. [ 1 ]


The relative effectiveness of surgical options for treating fecal incontinence is not known. [ 2 ]  A combination of different surgical and non-surgical therapies may be optimal. [ 2 ]  A surgical treatment algorithm has been proposed for FI, [ 3 ]  although this did not appear to include some surgical options. Isolated sphincter defects may be initially treated with sphincteroplasty and if this fails, the patient can be assessed for sacral nerve stimulation. Functional deficits of the external anal sphincter (EAS) and/or internal anal sphincter (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.


This operation aims to repair sphincter defects (which may be of unknown cause) or damage from trauma (usually caused by obstetric damage). Where the sphincter has separated from a tear, this procedure brings these ends back together. Primary sphincteroplasty is repair carried out soon after the trauma has occurred, whilst other repairs may be carried out years after the original trauma (secondary or delayed sphincter repair), usually because the trauma went unrecognised. Usually, sphincter defects are in the anterior position on the sphincter, when an anterior sphincteroplasty may be carried out. Where the sphincter defect is laterally or posteriorly placed, this carries a less successful outcome. [ 3 ] [ 4 ] [ 5 ]  Overlapping anterior sphincteroplasty is preceded by a bowel preparation and possibly antibiotics. Once the patient is under anesthesia, an incision is made in front of the anus (the anterior perineum). Scar tissue is removed and the mucosa of the anal canal separated from the damaged sphincter. The sphincter is cut and its ends overlapped and then stitched back together. The exact method of the procedure varies, e.g. the cut sphincter may be stitched back end to end, rather than overlapped, or the IAS and EAS may be repaired as separate stages. Sphincter repair may sometimes be combined with an anterior levatorplasty (an operation to tighten the pelvic floor). A surgical drain is left to prevent buildup of fluid. After the operation,  sitz baths  are recommended to maintain hygiene during healing, and laxatives prescribed to avoid hard stool. [ 5 ]  Overlapping anterior sphincteroplasty improves FI symptoms in the short term in most (50-80%) patients with sphincter defects. Thereafter, continence deteriorates. Most who undergo this operation are incontinent again after 5 years. Poor results with this procedure may be related to pelvic floor denervation (nerve damage). Primary sphincter repair is inadequate in most women with obstetric ruptures following vaginal delivery. Residual sphincter defects remain in most and around 50% remain incontinent. If there is a residual sphincter defect following the operation (as demonstrated by endoanal ultrasonography), then the procedure may be repeated. [ 4 ] [ 5 ]


This procedure aims to improve FI by restoring the anorectal angle and lengthen the anal canal.  The main indication is denervation of the pelvic floor (e.g. descending perineum syndrome). After the patient is anesthetized, an incision is made posterior to (behind) the anus and a space between the EAS and IAS is opened up. This plane is followed, freeing the rectum from its attachment to the pelvic floor. Puborectalis and pubococcygeus are folded and held with stitches. These folds will lengthen the anal canal. It is safe and simple, but long term improvements in FI are poor (30-40%). Total pelvic floor repair refers to a procedure combining postanal and anterior anal repair. [ 5 ]


These procedures aim to inject  bio-compatible  material into the walls of the anal canal, aiming to bulk out these tissues. This may bring the walls of the anal canal into tighter contact, raising the resting pressure, creating more of a barrier to the loss of stool, and thereby reducing FI. Originally, this technique was described for urinary incontinence, but was first used for FI in 1993, [ 6 ]  especially passive soiling due to IAS dysfunction. The procedure can be carried out under  local anesthetic  on an  out patient  basis, or with  caudal epidural anesthesia , [ 7 ]  or with  intravenous sedation , or under  general anesthesia . [ 8 ]  This measure has many advantages over more invasive surgery, since there are rarely any serious complications. [ 8 ]  Many different materials have been used as perianal injectable bulking agents. [ 9 ]  Of the available materials, which one is the best is not known. [ 7 ]