In 1992 a new strain appeared in Asia, a non-O1, nonagglutinable vibrio (NAG), which was named O139 Bengal. It was first identified in  Tamil Nadu , India, and for a while displaced El Tor in southern Asia. It decreased in prevalence from 1995 to around 10 percent of all cases. It is considered to be an intermediate between El Tor and the classic strain, and occurs in a new serogroup. Scientists warn of evidence of wide-spectrum resistance by cholera bacteria to drugs such as  trimethoprim ,  sulfamethoxazole  and  streptomycin . [ citation needed ]


A persistent  urban myth  states 90,000 people died in Chicago of cholera and  typhoid fever  in 1885, but this story has no factual basis. [ 129 ]  In 1885, a torrential rainstorm flushed the  Chicago River  and its attendant pollutants into  Lake Michigan  far enough that the city's water supply was contaminated. But, as cholera was not present in the city, there were no cholera-related deaths. As a result of the pollution, the city made changes to improve its treatment of sewage and avoid similar events. [ citation needed ]


Unlike  tuberculosis  ("consumption"), which in literature and the arts was often romanticized as a disease of denizens of the  demimondaine  or those with an artistic temperament, [ 130 ]  cholera is a disease that today almost entirely affects the lower-classes living in filth and poverty.  This, and the unpleasant course of the disease – which includes voluminous "rice-water" diarrhea, the hemorrhaging of liquids from the mouth, and violent muscle contractions which continue even after death – has discouraged the disease being romanticized. It is seldom presented at all in popular culture. [ 131 ]


Human feces  ( American English ) or  faeces  ( British English ), commonly and in medical literature more often called  stool , [ 1 ]  are the solid or semisolid remains of food that could not be digested or absorbed in the  small intestine  of humans, but has been further broken down by bacteria in the  large intestine . [ 2 ] [ 3 ]  It also contains bacteria and a relatively small amount of  metabolic waste  products such as bacterially altered  bilirubin , and the dead epithelial cells from the lining of the gut. [ 2 ]  It is discharged through the  anus  during a process called  defecation .


Human feces has similarities to the feces of other animals and varies significantly in appearance (i.e. size, color, texture), according to the state of the  diet ,  digestive system , and general  health . Normally, human feces are semisolid, with a  mucus  coating. Small pieces of harder, less moist feces can sometimes be seen impacted in the  distal  (final or lower) end. This is a normal occurrence when a prior  bowel movement  is incomplete, and feces are returned from the  rectum  to the large  intestine , where water is further absorbed.


Human feces together with human  urine  are collectively called  human waste  or  excretion . Containing human feces and preventing spread of  pathogens  from human feces by the  fecal–oral route  are the main goals of  sanitation .


The Bristol stool scale is a  medical  aid designed to classify the form of human feces into seven categories. Sometimes referred to in the UK as the Meyers Scale, it was developed by K.W. Heaton at the  University of Bristol  and was first published in the  Scandinavian Journal of Gastroenterology  in 1997. [ 4 ]  The form of the stool depends on the time it spends in the  colon . [ 5 ]


The seven types of stool are:


Types 1 and 2 indicate  constipation . Types 3 and 4 are optimal, especially the latter, as these are the easiest to  pass . Types 5–7 are associated with increasing tendency to  diarrhea  or urgency. [ 5 ]


Meconium  is a newborn  baby 's first feces.


Human fecal matter varies significantly in appearance, depending on diet and health.


Feces possesses physiological odor, which can vary according to diet and health status. For example, meat protein is rich in the amino acid  methionine , which is a precursor of the sulfur-containing odorous compounds listed below. [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ]  The odor of human feces is suggested to be made up from the following odorant volatiles: [ 13 ]


(H 2 S) is the most common volatile sulfur compound in feces. [ 13 ]  The odor of feces may be increased when various pathologies are present, including: [ 17 ]


Attempts to reduce the odor of feces (and  flatus ) are largely based on animal research carried out with industrial applications, such as reduced environmental impact of pig farming. See also:  Flatulence#Management , odor. Many dietary modifications/supplements have been researched, including:


On average, healthy humans eliminate 128 g of fresh feces per person per day with a  pH value  of around 6.6 as indicated by a  Fecal pH test . [ 23 ]  Fresh feces contains around 75% water and the remaining solid fraction is 84–93% organic solids along with some insoluble phosphate salts.


These organic solids consist of: 25–54% bacterial biomass, 2–25% protein or nitrogenous matter, 25% carbohydrate or undigested plant matter, and 2–15% fat. Protein and fat come from the colon due to secretion, epithelial shedding, and gut bacterial action. These proportions vary considerably depending on many factors but mainly  diet  and  body weight . [ 24 ]  The remaining solids are composed of insoluble calcium and iron phosphate salts, intestinal secretions, small amounts of dried  epithelial  cells, and  mucus . [ 24 ]


Sometimes undigested food may make an appearance in feces. Common undigested foods found in human feces are seeds, nuts, and corn, mainly because of their high  fiber  content. Beets may turn feces different hues of red. Artificial food coloring in some processed foods, such as highly colorful packaged breakfast cereals, can cause an unusual coloring of feces if eaten in sufficient quantities.


Undigested objects such as seeds can pass through the human digestive system, and later  germinate . One result of this is  tomato  plants growing where treated  sewage sludge  has been used as  fertilizer .


Clinical laboratory examination of feces, usually termed as stool examination or  stool test , is conducted for the sake of diagnosis; for example, to detect the presence of parasites such as  pinworms  and their eggs (ova) or to detect disease-spreading bacteria. A  stool culture —the controlled growth of microbial organisms in  culture media  under laboratory conditions—sometimes is performed to identify specific pathogens in stool. The  stool guaiac test  (or guaiac fecal occult blood test) is conducted to detect the presence of blood in stool that is not apparent to the unaided eye.


The main pathogens that are commonly looked for in feces include:


Intestinal parasites  and their  ova  (eggs) can sometimes be visible to the  naked eye .


Feces can be analyzed for various markers that are indicative of various diseases and conditions. For example,  fecal calprotectin  levels indicate an inflammatory process such as  Crohn's disease ,  ulcerative colitis , and  neoplasms  ( cancer ).


Also, feces may be analyzed for any  fecal occult blood , which is indicative of a  gastrointestinal bleeding .


A quick test for fecal contamination of water sources or soil is a check for the presence of  E. coli   bacteria  performed with the help of  MacConkey agar  plates or  Petri dishes .  E. coli  bacteria uniquely develop red colonies at temperature of approximately 43 °C (109 °F) overnight. Although most strains of  E. coli  are harmless, their presence is indicative of fecal contamination, and hence an increased possibility of the presence of more dangerous organisms.


Fecal contamination of water sources is highly prevalent worldwide, accounting for the majority of unsafe  drinking water . In  developing countries  most sewage is discharged without treatment. Even in  developed countries  events of  sanitary sewer overflow  are not uncommon and regularly pollute the  Seine River  ( France ) and the  River Thames  ( England ), for example.


Diarrhea (or diarrhoea in  British English ) is the condition of having three or more loose or liquid  bowel movements  per day. [ 26 ]  This condition can be a symptom of injury,  disease , or  foodborne illness  and is usually accompanied by abdominal pain. There are other conditions which involve some but not all of the symptoms of diarrhea, and so the formal medical definition of diarrhea involves defecation of more than 200 grams per day (though formal weighing of stools to determine a diagnosis is never actually carried out).


It occurs when insufficient fluid is absorbed by the colon. As part of the  digestion  process, or due to fluid intake,  food  is mixed with large amounts of water. Thus, digested food is essentially liquid prior to reaching the colon. The colon absorbs water, leaving the remaining material as a semisolid stool. If the colon is damaged or inflamed, however, absorption is inhibited, and watery stools result.


Diarrhea is most commonly caused by a myriad of  viral  infections but is also often the result of  bacterial  toxins and sometimes even infection. In sanitary living conditions and with ample food and water available, an otherwise healthy patient typically recovers from the common viral infections in a few days and at most a week. However, for ill or malnourished individuals diarrhea can lead to severe  dehydration  and can become life-threatening without treatment.


Constipation refers to  bowel movements  that are infrequent or hard to pass. [ 27 ]  Constipation is a common cause of painful defecation. Severe constipation includes obstipation (failure to pass stools or gas) and  fecal impaction , which can progress to  bowel obstruction  and become life-threatening.


Bile  overload is very rare, and not a health threat. Problems as simple as serious  diarrhea  may cause blood in one's stool. Black stools caused by the presence of blood usually indicate a problem in the intestines (the black color is a sign of digested blood), whereas red streaks of blood in stool usually are caused by bleeding in the rectum or anus.


Human feces has historically been used as  fertilizer  for centuries in the form of  night soil ,  fecal sludge , and  sewage sludge . The use of untreated human feces in agriculture poses significant health risks and has contributed to widespread infection with  parasitic worms —a disease called  helminthiasis , affecting over 1.5 billion people in developing countries.


There are methods available to safely reuse human feces in  agriculture  as per the "multiple barrier concept" described by the  World Health Organization  in 2006. [ 28 ]  The approach to "close the loop" between human excreta ( sanitation ) and agriculture is also called  ecological sanitation . It may involve certain types of  dry toilets  such as  urine-diversion dry toilets  or  composting toilets .


In humans, fecal transplants (or  stool transplant ) is the process of transplantation of fecal bacteria from a healthy individual into a recipient who has a certain disease, such as  irritable bowel syndrome . The resulting  inoculation  of healthy  gut flora  can sometimes improve the physiology of the recipient gut.


Fecal bacteriotherapy —also known as a fecal transplant—is a medical procedure wherein fecal bacteria are transplanted from a healthy individual into a patient. [ 29 ] [ 30 ]  Recent research indicates that this may be a valuable method to re-establish normal gut cultures that have been destroyed through the use of antibiotics or some other medical treatments.


The  biogas  produced from feces when it is contained in  sewage  and treated in an  anaerobic digestion  process could be worth as much as US$9.5 billion. [ 31 ]


Washington DC plans to produce biogas from  sewage sludge , the by-product of  sewage treatment , which will save US$13 million a year. [ 32 ]  Teams from the Cambridge Development Initiative, led by Stanford researcher Maisam Pyarali, began a project in 2015 to convert sewage from the slums of  Dar Es Salaam  into biogas and fertilizer with solar concentrators. [ 33 ]


Paleofeces , also known as coprolites (though that name is more commonly used in reference to animal feces), are ancient human feces, often found as part of  archaeological  excavations or surveys. Intact feces of ancient people may be found in caves in arid climates and in other locations with suitable preservation conditions. These are studied to determine the diet and health of the people who produced them through the analysis of seeds, small bones, and parasite eggs found inside. They also may be analyzed chemically for more in-depth information on the individual who excreted them, using  lipid analysis  and  DNA analysis . The success rate of usable DNA extraction is relatively high in paleofeces, making it more reliable than skeletal DNA retrieval. [ 34 ]


In most human cultures, feces elicit varying degrees of  disgust . Disgust is experienced primarily in relation to the sense of taste (either perceived or imagined) and, secondarily to anything that causes a similar feeling by sense of smell, touch, or vision. As such, human feces are regarded as something to be avoided diligently: expelled in private and disposed of immediately and without a trace. It often is considered an unacceptable topic in polite conversation and its mere mention may cause offence in certain contexts.


An example of repulsion by feces from the  ancient world  is found in the writings called  Deuteronomy  used by  Jews  and  Christians :


Designate a place outside the camp where you can go to relieve yourself. As part of your equipment have something to dig with, and when you relieve yourself, dig a hole and cover up your excrement. For the LORD your God moves about in your camp to protect you and to deliver your enemies to you. Your camp must be holy, so that he will not see among you anything indecent and turn away from you. [ 35 ]


Evolution can explain this disgust since feces are a significant disease vector, carrying many kinds of microorganisms that can sicken humans, including  E. coli .


People from different cultures employ a variety of personal cleansing practices after defecation. The  anus  and  buttocks  may be either washed with liquids or wiped with  toilet paper  or other solid materials. In many  Muslim ,  Hindu  and  Sikh  cultures, as well as  Southeast Asia  and Southern Europe, water is usually used for anal cleansing using a jet, as with a  bidet , or most commonly, splashed and washed with the hand. In other cultures (such as many  Western countries ), cleaning after defecation is generally done with  toilet paper  only.


There are many synonyms in informal  registers  for human feces. Many are  euphemistic ,  colloquial , or both; some are  profane  (such as  shit ), whereas most belong chiefly to  child-directed speech  (such as  poo  or  poop ) or to  crude humor  (such as  turd ). An example of an euphemistic term for feces is  number two .


Human feces together with human  urine  are collectively referred to as  human waste  or human  excreta .


In  medicine , the  ileal pouch–anal anastomosis  ( IPAA ), also known as  restorative proctocolectomy  ( RPC ),  ileal-anal reservoir  ( IAR ), an  ileo-anal pouch ,  ileal-anal pullthrough , or sometimes referred to as a  J-pouch ,  S-pouch ,  W-pouch , or a  pelvic pouch , is an  anastomosis  of a reservoir pouch made from  ileum  (small intestine) to the  anus , bypassing the former site of the  colon  in cases where the colon and rectum have been removed. The pouch retains and restores functionality of the anus, with stools passed under voluntary control of the person, preventing  fecal incontinence  and serving as an alternative to a total proctocolectomy with  ileostomy .


During a total proctocolectomy, a surgeon removes a person's diseased colon, rectum, and anus. [ citation needed ]   For the ileostomy, the end of the small intestine is brought to the surface of the body through an opening in the abdominal wall for waste to be removed.  People with ileostomies wear an external bag, also known as an  ostomy system  or stoma appliance, to collect waste which can be emptied and changed as needed.


With an optional ileo-anal pouch procedure, the pouch component is a surgically constructed internal intestinal reservoir; usually situated near where the  rectum  would normally be. It is formed by folding loops of small intestine (the  ileum ) back on themselves and stitching or stapling them together. The internal walls are then removed thus forming a reservoir often referred to as a 'pouch'. The reservoir is then stitched or stapled into anal area where the bottom of the rectum was.  The first pouch anal-anastomosis surgery in the world was performed by British surgeon  Sir Alan Parks  in 1976 at the London Hospital (called the  Royal London Hospital  since 1990).  After the first surgery, he continued to develop the procedure at  St Mark's Hospital  in London along with his colleague  John Nicholls . [ 1 ]


Pouch surgery is elective, meaning it is entirely optional, and should be done on the basis of choice by people who doctors deem suitable for a pouch after medical evaluations.  Pouch surgery is considered reconstructive with the benefit being for quality of life and not disease removal, similar in theory to a breast reconstruction after a mastectomy removes diseased breast tissue.  Before a pouch is created, a person's diseased colon and rectum are removed.  After disease removal, standard medical screening exams for pouch candidates include but are not limited to biopsies, radiology imaging, sphincter function tests, fertility consultations for people of childbearing age with the wish to get pregnant, and psychological support due to intensity of the pouch operations. [ 2 ]


A similar ileal pouch without the anal anastomosis is a  Kock pouch .  A Kock pouch is also called a 'continent ileostomy' because while a person has a pouch constructed inside their body, it is located near the abdominal wall and empties via a stoma from the ileum at the person's convenience. [ 3 ]   A Kock pouch does not restore the anal function.  The procedure was first premiered by Finnish surgeon  Nils Kock  in Sweden during 1969.  It was an evolution in bowel surgery because it created an ileum pouch for storage of waste inside the body eliminating the need for an external bag for waste collection.  An  ileostomy  without a Kock pouch functions constantly, meaning, a patient with ileostomy by itself is incontinent because waste is always moving down the bowel and thus the need for an external appliance bag.  Kock pouch surgery is also elective surgery that only provides a reconstructive benefit after disease removal.  It should be the patient's optional choice based on how a person wants to live their life.


Ileo-anal pouches are constructed for people who have had their  colon  and  rectum  surgically removed due to disease, injury, or infection. Several diseases and conditions may trigger the need for surgical removal. [ 4 ]


There is debate about whether patients with  Crohn's disease  and  indeterminate colitis  are suitable candidates for an ileo-anal pouch due to the risk of the disease occurring in the pouch. Crohn's disease can manifest in many different parts of the digestive tract, so the removal of the colon and creation of a pouch, while alleviating symptoms that occurred in the large intestine plus possibly the rectum, does not eliminate Crohn's disease. [ 6 ] [ 7 ]


Additional contradictions that may prevent a person from being able to undergo pouch surgery include but are not limited to weak sphincter muscles, advanced age (elderly) due to the higher risk of fecal incontinence, pelvic radiation therapy, and women with a history of obstetric complications. [ 8 ]


Ileum pouch surgery (Kock and IPAA) are  reconstructive procedures .  Reconstructive procedures do not cure disease.  Since they are not  curative , reconstructive surgeries are not medically necessary, meaning they are elective operations.  Several words can be used to describe an ' elective surgery ' including optional and patient's choice.  Pouch reconstruction should never be offered as the only option to a person because it is elective and should be a voluntary choice offered alongside other options that are safe for the person's individual circumstances. [ 9 ]


While both  ulcerative colitis  (UC) and  familial adenomatous polyposis  (FAP) patients and are sometimes controversially considered cured of problematic symptoms after pouch creation due to the removal of disease activity in the colon and rectum, there are still many complications that can arise. While life with a pouch is typically viewed by some people plus some medical professionals as a significant improvement compared to life with an ileostomy, patients living with a pouch may still face daily pains and discomforts including the inability to sleep through the night, a changed diet, severe or frequent gas pain, nutrient deficiencies, and the inability to digest certain foods.


With regards to  ulcerative colitis  (UC), the disease is a systemic  immune mediated inflammatory disease , also often referred to as an  autoimmune  condition. [ 10 ]   The main risk UC presents is typically inflammation that causes ulcers in the lining of the colon and rectum.  This common expression happens in the mucosal layer of the intestine that is only present in the colon and rectum (not the small intestine), which is why the disease was named 'ulcerative colitis'.  Therefore, ulcerative colitis is considered 'cured' of the problematic disease activity in the colon and rectum only, after both the large intestine and rectum are removed.  Reasons to remove this mucosal layer include severe discomfort that reduces quality of life, bowel perforation from inflammation, and development of tumors that are cancerous from long-term inflammation.


Even after a person has their colon and rectum removed, the circumstances that created ulcerative colitis still lives on inside that person's body because it is a systemic  immune mediated  condition.  These conditions occasionally manifest in other ways including additional illnesses considered related to ulcerative colitis like  primary sclerosing cholangitis  (PSC) in the liver, the eye condition  uveitis , and certain forms of  arthritis  throughout the body.


It is important to understand that pouch surgery does not cure a patient of ulcerative colitis, removal of the diseased mucosal layer in the colon and rectum cures the disease in the colon and rectum only, if the entire colon and full rectum are removed.  For example, if a rectal remnant remains, UC disease can be retained in the small remnant.  Active disease feels similar to ulcerative proctosis when the full natural rectum was in place.  It is also medically treated the same way ulcerative proctosis was before any surgery.  Even if the entire colon and rectum are removed to stop disease activity in this area, the underlying reasons for the expression of the disease in the large bowel and rectum's mucosal layer remain with the person. [ 11 ]


A pouch should never be offered as the only treatment option due to the fact it is  reconstructive  and not  curative .  People who need to have their colon and rectum removed are usually presented with several options including total proctocolectomy with end ileostomy ("Barbie" or "Ken" butt), colectomy with rectum left in place, pelvic pouch (ileo-anal pouch / IPAA), ileo-rectum anastomosis (IRA), or continent ileostomy such as a Kock pouch, for example, if someone has weak  sphincter  muscles or a diseased anus.  The end decision should always be the patient's choice, based on if their health permits the option to have a good outcome. [ 12 ] [ 13 ]


Pouch surgery comes with a number of well known complications that a person will not be able to imagine as possibilities themselves, therefore, as part of the education and  informed consent  process before pouch creation surgery is scheduled, risks, complications, and safe alternatives need to be communicated. [ 14 ] [ 15 ]   If a person has  indeterminate colitis , they should also be informed before a pouch is recommended and created that their pathology is unknown due to the even higher risk indeterminate folks face. [ 16 ] [ 17 ]


The most common complication of pouch surgery is an umbrella term called pouchitis that encompasses many causes of inflammation of the pouch.  The word 'pouchitis' simply means 'pouch inflammation' similar to 'tonsillitis' meaning 'tonsil inflammation' or 'sinusitis' meaning 'sinus inflammation'.  While ulcerative colitis pouch patients may experience a dysbiosis sparked type of inflammation more than people who get a pouch because of cancer or FAP, pouchitis can be caused by a number of factors in any pouch. [ 18 ]   Pouchitis is grouped into four main categories of origin: inflammatory, mechanical, surgical, or functional.  Pouchitis, meaning pouch inflammation from various root causes, can be a driver of pouch dysfunction for some. [ 19 ]


The surgical procedure for forming an ileal pouch-anal anastomosis (IPAA) was pioneered by  Sir Alan Parks  at the London Hospital, today called the  Royal London Hospital , in 1976.


Parks' pouch surgery was originally envisioned as a quality of life enhancing procedure for people who needed to have their colon and rectum removed.  People who opted to have the procedure would be able to avoid an ileostomy by restoring intestinal continuity with elective, or optional, ileo-anal pouch surgery.  Shortly after performing the world's first few pouch procedures in 1976, Sir Alan along with  John Nicholls  joined  St Mark's Hospital  also in London where they continued to develop the intestinal pouch procedure.  The pair first published details of the procedure in the  British Medical Journal  in 1978 with the article "Proctocolectomy without ileostomy for ulcerative colitis". [ 20 ]


Sir Alan Parks' ileo pouch-anal anastomosis (IPAA), was a surgical advancement from the ileoanal anastomosis procedure developed in the 1940s.  With an ileum-anal anastomosis, the entire colon and rectum were removed.  Next a surgical join (anastomosis) was used to connect the end of the small intestine (ileum) to the anus.  It was described by the German surgeon Nissen in 1934 and American surgeons Ravitch and Sabiston in 1947.  The ileum-anal anastomisis [ check spelling ]  was reported to have a high of frequency of liquid movements making it uncomfortable for many people. [ 21 ]   It was also a surgical advancement from the  Kock pouch  first performed in Sweden by Finnish surgeon  Nils Kock  in 1969 because Parks' ileum pouch-anal anastomosis (IPAA), unlike Kock's 'continent ileostomy' allowed for restoration of anal evacuation.


The original Sir Alan S-pouches had a bit of intestine at the bottom of the design that often made them difficult to evacuate.  Some patients later underwent advancement surgery to remove the extra tip of small intestine and lower the pouch directly onto the anus to remedy evacuation difficulties. [ 22 ]


In 1980, surgeons in Japan published the first study on the J-shaped pouch. J. Utunomiya is created with its creation. [ 23 ]   The J-shaped pouch design eliminated the 'conduit' or bit of intestine at the bottom of Sir Alan Parks' S-pouch formation making it easier for people to empty a J-pouch.  As intestinal pouch surgery became more common, the J-pouch eventually became the dominant shape.  J-pouches are easier for surgeons to construct than the hand sewn S or W formations because the Js are from two loops of ileum plus with the invention of the stapler, Js could be stapled, instead of hand-sewn.  J-pouches are considered faster and easier to make over Ss and Ws. [ 24 ] [ 25 ]


The same year as Sir Alan Parks' unexpected death in 1982, his St Mark's Hospital colleague,  John Nicholls  premiered the W-pouch which was an augmentation of the J-pouch made to expand the pouch's capacity and reduce the person's frequency of bowel movements. [ 26 ]   Nicholls' W-pouch is explained as two J-pouches placed together to make the higher capacity W-pouch.


The W-pouch was entirely hand-sewn and required a very experienced and highly skilled surgeon plus more time in the operating room. [ 27 ] [ 28 ]   A J-pouch was not as technical and therefore, more surgeons could perform the procedure.


In the United States, Australian born colorectal surgeon  Victor Warren Fazio  was a driving force behind the procedure's adaptation into American colorectal surgery offerings.  He established the  Cleveland Clinic 's prestigious pouch practice in 1983 when the clinic performed its first pouch surgery.  In 2002 the Cleveland Clinic opened the world's first pouch center with its "Ileal Pouch Center".


About the same time as the Cleveland Clinic began offering the restorative proctocolectomy procedure (RPC), surgeons at the  Mayo Clinic  in Minnesota also started offering it to suitable patients including Roger R. Dozois who published several early studies on the pouch operation in the United States. [ 29 ] [ 30 ]


By the early 1980s, the ileal pouch procedure had become part of specialist colorectal surgical practices not just in the United Kingdom and United States but worldwide.  Following the unexpected death of  Sir Alan Parks  in 1982, his colleague  John Nicholls  along with the pouch surgery team at  St Marks Hospital  collaborated with a number of leading hospitals globally to share pouch surgery knowledge Zane Cohen is credited with being a leader in Canada's development of pouch surgery. [ 31 ] [ 32 ]  Rolland Parc was a force behind its early evolution in France. [ 33 ]  Gilberto Poggioli is credited with being at the forefront of establishing the pouch a surgical offering in Italy. [ 34 ] [ 35 ] [ 36 ]


It is generally considered best practice to create and manage ileum pouches at a facility that has specialized and experienced clinicians specifically for intestinal pouch care.  Individual doctors and facilities can communicate their level of pouch experience to potential pouchees, people already living with a pouch interested in continued care, or loved ones who care for a person eligible for pouch construction surgery, or for loved ones already with a pouch.  Colorectal ,  coloproctology , and/or  proctology surgeons  should be able to communicate their pouch surgery success and failure rates.  Gastroenterologists  and surgeons should also be able to refer people to pouch specialists for a second opinion on an existing recommendation or for continued pouch care.


Intestinal pouches are considered optional reconstructive procedures to be done by the patient's choice since pouch surgery itself does not cure disease.  Pouch surgery can only take place after disease is removed.  Many national gastroenterology associations including the  British Society of Gastroenterology  (BSG) [ 37 ]  and the European Crohn's and Colitis Organisation (ECCO) [ 38 ]  recommend that pouches should ideally be created at facilities that have specialized pouch centers when possible due to the high level of technical skill required for multidisciplinary management of a pouch.  Numerous studies also show that there is a direct relation between the success of a pouch and the experience a surgeon has with previous pouch creations. [ 39 ] [ 40 ]


In addition to specialized doctors for colorectal surgery, gastroenterology, pathology, radiology, gynecology and urology, fertility, psychology, nutrition, and rehabilitation including physiotherapy, facilities with pouch centers often also have a specialized pouch nurse or pouch nursing team.  The pouch nurse is usually an extension of the IBD nursing team or stoma nurse team.  However, pouch nurses are also trained for pouches created from injury, infection, FAP, cancer and other reasons.  Pouch nurses provide healthcare, advice, and support specific to the concerns of pouch patients before and after surgery. [ 41 ] [ 42 ]


In this elective and reconstructive  surgical procedure , a pouch, or intestinal reservoir, made from  ileum  (small intestine) is attached to the  anus  after the  colon  (large intestine) and  rectum  have been removed.


The entire procedure can be performed in one operation, but is usually split into two or three procedures based on the person's overall health at the time of surgery.


If a colectomy is planned, and not done as an emergency due to severe injury or illness and the person is in good health, some surgeons will recommend a two-step procedure.  When done as a two-step, the first operation (step one) involves a  proctocolectomy  (removal of the large intestine and rectum), and fashioning of the pouch. The patient is given a temporary defunctioning  ileostomy  (also known as a "loop ileostomy"). After a healing period determined by the surgeon based on the individual patient, the second step is performed, in which the ileostomy is reversed. This step is referred to as ileostomy reversal or takedown.  The reason for the temporary ileostomy is to allow the newly constructed pouch to fully heal without waste passing through it, thus avoiding leaks that can lead to infection. [ 44 ]


When a colectomy is performed as an emergency (which can arise from  toxic megacolon  and other complications including infection), or when the patient is extremely ill, the colectomy and pouch construction are performed in separate stages, resulting in a three-part surgery. [ 45 ]


Outside of serious illness, some surgeons also prefer to perform a  subtotal colectomy  (removing all the colon except the  rectum ) first, since removal of the rectum can lead to complications with the anal  sphincters . After the subtotal colectomy, the second operation consists of pouch creation with installation of a double or loop ileostomy to protect the pouch while it heals.  Waste continues to exit through an opening in the abdominal wall.  Then usually three to six months later when surgeons feel the pouch has healed, the loop stoma is reversed and the pouch becomes fully operational restoring intestinal continuity. [ 46 ]


Just as debate continues on which formation of pouch functions best, there is also an ongoing discussion about the pouch's type of anal anastomosis - or method used to attach the pouch to the anal canal.  Both methods have risks and benefits.


The pouch can also be formed as part of a three step procedure for people of childbearing age who have not completed their family planning.  When there is a wish for pregnancy, the process can be paused after subtotal colectomy until family planning is complete if doctors feel remaining disease in the rectum, if any, can be safely managed until removal during pouch creation.


A fall in female fertility was reported in a Danish study by Olsen et al. in 1999 showing a drop after pouch surgery to less than 50% of the normal population. [ 51 ]   There are well researched risks to fertility for both men and women.  Highly specialized pouch centers globally typically offer fertility counselling as part of their patient selection and informed consent process. [ 52 ]


A rare risk to male fertility is nerve damage that impairs or prevents ejaculation.  Risks to fertility for women include removal of the rectum reducing fertility by at least 50%, a dysfunctional pouch sparking a hostile environment in the pelvis preventing embryo implementation in the uterus and scar tissue formation over fallopian tubes blocking ovulation, although, scar tissue formation appears to be less likely with laparoscopic than open surgery. [ 53 ]


Women who choose the option to undergo pouch surgery before childbirth, should also undergo a fertility evaluation before surgery that includes an egg preservation consultation especially if she is over the age of 35 years.  With the pouch surgery potentially reducing fertility, the  in vitro  fertilization  (IVF) treatment a younger woman experiencing pouch related infertility may need to rely on to conceive, may not legally be available to the older woman if she later learns past the cutoff-age that her situation requires IVF to get pregnant.  Most women are not aware of age limits to IVF treatment using their own eggs - especially if they are living, studying, or working away from their hometown or abroad at the time of their operations. [ 54 ] [ 55 ] [ 56 ] [ 57 ]


The general public's lack of widespread knowledge about IVF regulations also applies to child adoption laws.  Most men and women are not aware that some countries place age bans on adopting newborns.  For example, in Germany adoption of an infant is prohibited if a parent is over the age of 40 years.  These adoption age bans combined with the risk of pouch related fertility complications, plus potential IVF age cut-off limits then increases the need for a person to plan to preserve fertility before pouch surgery commences in order to improve chances of later completing a wish for a family. [ 58 ] [ 59 ] [ 60 ]


While most people who undergo elective reconstructive pouch surgery have either no issues or occasional minor discomfort, some pouches experience more serious complications that need medical management with a variety of therapies including medication and/or additional surgery.
 [ 61 ] [ 62 ] [ 63 ]


Pouchitis  is a general term that refers to a wide spectrum of diseases and conditions that cause inflammation of the pouch. It is a common complication after IPAA/RPC. People report many symptoms including abdominal pain or cramps, increased bowel frequency, urgency of movements, strong evacuation urges, daytime incontinence, nocturnal seepage, and/or rectal bleeding. Studies show pouchitis occurs more often in people who got their pouch because of ulcerative colitis rather than familial adenomatous polyposis (FAP) which suggests that the pathogenic (microbial) background of UC may contribute to the development of pouchitis in some pouches. [ 18 ]


Diagnosis of pouchitis:
Pouchitis is diagnosed based on the presence of symptoms together with endoscopic and histological evidence of pouch inflammation. For example, biopsies may be taken during a pouchoscopy (a camera exam like a colonoscopy but for the pouch) to rule out infection from  Clostridioides difficile  infection  (C-diff) or  Cytomegalovirus  (CMV). Treatment of infections usually begins with antibiotics and may also include multi-strain probiotics.


After exams and tests, pouchitis is divided into two categories based on findings: idiopathic or secondary. In idiopathic pouchitis, the cause of inflammation is still unclear. With secondary pouchitis, there is an association with a specific causative or pathogenetic factor. Secondary pouchitis can be classified into subgroups. It is possible to have one or more causes of pouch inflammation at the same time. [ 64 ] [ 65 ]


Antibiotic therapy for pouchitis:
Standard treatment of pouchitis when first reported (acute pouchitis) without any other obvious cause identified such as infection or anal join leak (fistula) is oral antibiotics for two weeks, typically ciprofloxacin 500 mg every 12 hours.  Alternatives to ciprofloxacin for initial therapy include metronidazole 500 mg (twice daily) or tinidazole 500 mg (twice daily). [ 65 ]


For pouches with acute idiopathic pouchitis, response to antibiotic therapy is typically examined clinically by asking the patient if they have experienced an improvement with their symptoms plus looking endoscopically using a pouchoscopy after completing antibiotic therapy. While endoscopic mucosal healing may lag behind symptomatic improvement, mucosal healing is a treatment target for patients with pouchitis. [ 66 ]


Cuffitis:
Cuffitis is inflammation of the retained rectal 'cuff' usually in a stapled pouch-anal anastomosis or the spot where the intestinal pouch was attached to the anus to restore anal evacuation.  Symptoms are typically similar to ulcerative proctosis for ulcerative colitis pouches including burning in the anal canal, a change in bowel movements, and sometimes rectal bleeding. [ 67 ]


Cuffitis diagnosis:
Most expert pouch centers plus national gastroenterology society guidelines worldwide recommend a cuff be no longer than 2 cm with the aim to staple the pouch at the level of the anorectal junction, [ 48 ] [ 68 ]  leaving about 1 cm of rectum or mucus layer behind for the staple to attach the pouch to the anus. [ 69 ] [ 67 ] [ 70 ]   This retained 1 to 2 cm of rectum can therefore, sometimes retain ulcerative colitis in UC pouches.  In contrast, hand sewn pouch-anal anastomosis' typically do not retain any mucus layer but sometimes a cuff is also used and it might cause discomfort for some hand sewn pouches.  Cuffitis is clinically diagnosed by symptoms plus endoscopically (pouchoscopy).


Treatment of cuffitis:
First-line therapy for acute cuffitis due to retained rectal mucosal layer is usually similar to the treatment for ulcerative proctosis that ulcerative colitis patients would have likely used before pouch surgery.  Mesalazine  suppositories or enemas are sometimes prescribed first (brand names include Asacol, Canasa, and Pentasa).  If those do not provide enough relief then treatment might be escalated to corticosteroid suppositories or enemas such as Budesonide.  Biological therapy may be prescribed if all other medical therapies fail to manage cuffitis and the person either is not suitable for or does not want to undergo a revision operation to remove the retained cuff and hand sew the pouch on the level of the dentate line (spot where anal skin changes to rectal mucus layer). [ 67 ] [ 71 ] [ 72 ] [ 73 ]


Crohn's disease of the pouch:
Some people undergoing IPAA/RPC may be later diagnosed with underlying Crohn's disease because the disease likely had not fully expressed itself at the time of surgery.  Crohn's disease of the pouch is associated with high failure rates.  Pouches may experience fistula leaks that cause pelvic sepsis and other complications. [ 74 ]


Treatment of Crohn's disease of the pouch:
If a person later diagnosed with Crohn's disease of the pouch wishes to keep their pouch operational, in some circumstances medical management might be possible.  Typically this is done with the prescription of biologics.  It may take more than one drug prescription to find a suitable biologic that encourages the desired anti-inflammatory response.


Celiac disease:
 Celiac disease  is an autoimmune condition that causes inflammation in the small intestine after gluten is eaten.  It can cause pouchitis symptoms and discomfort.  Some pouches that are celiac initially get misdiagnosed with Crohn's of the pouch.  Celiac disease is typically diagnosed by biopsy of the pouch. [ 75 ] [ 76 ]


Treatment of Celiac disease:
Typically, the first therapy approach to manage Celiac disease in person with an ileum pouch is dietary modification to reduce and/or eliminate gluten.


Other inflammatory conditions including IgG and IgG4:
Immunoglobulin related diseases can also cause problems for a pouch.  The two most common that are biopsied for are IgG and IgG4.  IgG molecules can initiate inflammatory reactions, both good and bad.  When the autoimmune reaction is inappropriate, a pouch might have problems with IgG.
IgG4 is a subclass of IgG.  IgG4 disease is a chronic immune-mediated fibroinflammatory disorder that can manifest with painless enlargement of organs or tumor-like masses. [ 77 ] [ 78 ] [ 79 ] [ 80 ]


Biopsies of the pouch should confirm if an infection is the root cause of pouch inflammation. If an infection from  Clostridioides difficile  (C-diff) or  Cytomegalovirus  (CMV) is found, initial therapy is usually antibiotics. [ 81 ] [ 82 ]  Certain infections such as a  Clostridioides difficile  (C-diff) might also be treated with probiotics just as a C-diff infection in a person who still has their colon would be treated. Probiotics that are prescribed for pouchitis (specifically pouchitis diagnosed as being caused by dysbiosis) are often also prescribed for C-diff. [ 83 ]


The pouch surgery itself can be the reason for some complications. [ 63 ]


Anastomotic leaks:
Anastomotic leaks occur on the lines where the pouch was sutured or stapled.  They usually occur close to the time of surgery but can appear months or years later.  When an anastomotic leak occurs, it can form a fistula or tract of fluid.


Fistulas:
Most fistulas will connect from an anastomotic leak to another area of the body such as a pouch-vagina fistula, perianal fistula, or presacral fistula with pelvic collection.  In some circumstances fistulas develop years after pouch creation due to the development of Crohn's disease.  Fistula's caused by Crohn's disease are often treated with biological therapy while a fistula from an anastomotic leak requires different therapies as biologics rarely help close a leak in a surgical suture or staple line of the pouch.  Different potential treatment options for an anastomotic fistula depend on the leak's location and include but are not limited to ENDO-Vac sponge, needle-knife therapy, draining seton, or cutting seton. [ 84 ] [ 85 ] [ 86 ] [ 87 ] [ 88 ]


Pelvic collection/sinus:
A pelvic collection or collection of fluid anywhere from a leak is called a sinus.  When an anastomotic leak is not treated promptly or does not heal it can cause pelvic sepsis.


Pelvic sepsis:
Pelvic sepsis also called peri pouch sepsis is a main cause of pouch failure and it creates conditions that make major revisionary surgery difficult.


Large or small pouch:
Standard guidelines for J-pouch construction is to use two loops of 15–20 cm ileum.  If the pouch is too small, the pouch will have a small volume.  This will increase the frequency of moments and could also be a cause of pouch failure. [ 63 ]


Pouch prolapse:
A pouch can either tilt or twist when stapled onto the anus causing prolapse. Pouch prolapse is also sometimes referred to as a floppy pouch. [ 90 ]   Pouch prolapse from a pouch being tilted or twisted can also cause pouch fistulas to develop, especially pouch-vagina fistulas.  Prolapse can also happen after the pouch is already in use.  With symptoms for pouch prolapse, a person typically has evacuation difficulties, seepage, pain, nausea, abdominal pain, or overt external prolapse of tissue. [ 91 ]


Strictures or stenosis
Narrowing of the anal canal under the pouch can cause evacuation difficulties.  Anal stricture can be a cause of pouch failure if not managed properly.  Anal stricture is a common complication of pouch surgery.  It is treated with dilatation or stretching under anesthesia.  Some people are also prescribed home dilatation routine using a  Hegar dilator  to manage chronic stenosis that keeps returning after dilatation. [ 92 ]


U-bend:
This happens when the surgeon fires the linear stapler and it malfunctions.  Usually the flaw is not noticed until after surgery is complete during first pouchoscopy.  The pouch is called a "U" bend because instead of stapling the two full sections of ileum together into a "J", the stapler does not create the 'J' but instead retains the shape of a 'U'.


Pelvic floor dysfunction and evacuation difficulties
Pelvic floor dysfunction is a common complication of pelvic surgery.  The Mayo Clinic believes it is an under reported complication of IPAA/RPC surgery with up to 75% of pouch patients experiencing non-relaxing pelvic floor dysfunction.  Biofeedback therapy is the main treatment for pelvic floor dysfunction. [ 93 ]


Cancer is a rare event after a pouch is created.  However, retained rectal mucosa can develop dysplasia over time especially if cuffitis is an ongoing complication.  Cancer can also develop in the pouch when there has been long-term pouchitis (inflammation of the pouch for any reason).  People who got their pouch as a result of bowel cancer may also experience cancer of the pouch. [ 94 ]


Removal of the entire large intestine (colon) and amounts of the terminal ileum at the end of the small intestine leads to fluid and nutritional absorption issues for all pouches.  The colon absorbs water, salts, and some key nutrients.  Dehydration can occur if a person does not get enough fluids.


The importance of ileum is that it absorbs key vitamins and minerals including  B12 ,  potassium , and  magnesium . In medical terms, low potassium is called  hypokalemia .  When a pouch is constructed small amounts of ileum are lost to the stomas and any stoma revisions.  The pouch itself is also made from ileum.  If a pouch is defunctioned (also explained as disconnected and/or pouch failure) the person also loses this extra amount of ileum when the pouch is disconnected from the digestive tract.


People with a pouch are at a further health risk if they experience excessive potassium loss due to things like vomiting, diarrhea, and prescription medications that increase urination. This is because potassium is a key electrolyte that helps regulate the heart and if levels become too low, a person can quickly become life-threateningly ill.  When levels are dangerously low, medical intervention with supplementation either orally or intravenously becomes necessary. [ 96 ]


Intestinal obstruction after ileal pouch-anal anastomosis (IPAA) surgery can occur due to various reasons such as adhesions (scar tissue ), strictures (narrowing at the anastomosis site), and Pouchitis (inflammation of the ileal pouch). [ 97 ]  Perforation at the site of attachment of the ileum to the rectum, or near the J-pouch, is a serious complication. [ 98 ] [ 99 ]  It can occur due to several reasons. But sometimes when pouchitis is not treated well, it gradually weakens the intestinal wall, which can eventually perforate.


When a pouch fails, suitable patients can choose to undergo surgery to repair the pouch or completely redo a pouch's anal-anastomosis or redo the entire pouch (if enough terminal ileum remains to produce a second pouch). [ 100 ] [ 101 ]   The cause of the problem that triggered a person's need for pouch salvage surgery will determine which method an experienced revision surgeon recommends as the surgical approach most likely to produce the best result possible.  Revisional surgeries are considered highly specialized. [ 102 ]   They require a skilled surgeon with complex revisional experience for the best chance at a good result.  Many expert pouch surgeons advocate for early referrals to specialists for best outcomes. [ 103 ]


Sometimes the root cause of pouch dysfunction can be managed with more conservative methods such as using an ENDO-Vac sponge for an anastomotic defect that leaks, needle knife therapy for fistulas and sinuses, or cutting seton for a low lying peri-anal fistula that does not impact the pouch's anal anastomosis (and many not even be related to the pouch itself).  When a more conservative method will not work or an attempt fails, bigger surgicial salvage procedures are then recommended, if the operation will have a chance to succeed and restore quality of life. [ 104 ] [ 105 ]


If a pouch has a troubled anal-anastomosis that leaks and causes sepsis or if a person retained more than the recommended amount of rectum (a rectal cuff of no more than 2 cm follows global colorectal surgery recommendations for an ulcerative colitis person), then an experience surgeon may be able to 'redo' the anal anastomosis by removing excess rectum.  Similarly, if a standard cuff of 1–2 cm was used, a revision surgeon still might be able to remove that and lower the pouch onto the anus.  In this scenario, the surgeon typically tries to save and reuse the existing pouch, but this is not always possible if the pouch is also damaged from complications or has technical flaws.  It might not be possible for an experienced salvage surgeon to redo an anal-anastomosis that has already been hand sewn or has a complication like a fistula or sepsis damage too close to the anus because this presents a surgical situation that is high risk to not heal properly and cause more complications. [ 106 ] [ 104 ] [ 107 ] [ 108 ] [ 109 ] [ 105 ]


If a person's pouch body is troubled, then an experienced pouch surgeon may be able to make a second pouch if the person's previous surgeries retained enough ileum to still safely create a second pouch.  Experienced revision surgeons will not create a second pouch if it risks putting the person into nutritional difficulties (including  short bowel syndrome ) because too much small bowel would be lost. [ 106 ] [ 104 ] [ 107 ] [ 108 ] [ 109 ] [ 105 ]


Occasionally, an experienced revision surgeon may need to alter the shape of the original pouch they are attempting to rescue.  For example, when there is not enough ileum to create a second pouch or if the person's anatomy (mesentery and/or vascular supply) does not allow for the pouch to reach to the anus.  This means the shape of a J-pouch may be transformed into an S, W, or even an H to repurpose functional ileum from the primary, or first pouch surgery, when retaining the original shape would not be successful but altering it could rescue the pouch situation. [ 110 ] [ 111 ] [ 112 ]


People can also choose to convert their failed ileo pouch-anal anastomosis (IPAA) to a continent ileostomy such as a  Kock pouch  in some circumstances. [ 113 ]


If a repair or redo can not be undertaken because of factors like severe disease, or a repeat surgery fails, or a patient wishes to have their pouch removed with undergoing additional surgery, a pouch excision operation can be performed to remove the pouch.  Removal of a pouch is a big operation that comes with complication risks. [ 114 ]


Ileo pouch-anal anastomosis surgery (IPAA) also called Reconstructive Proctocolectomy (RPC) was originally designed and premiered to improve quality of life for people who needed to have their colon and rectum removed because it avoided the need for stool collection in an external bag and restored the anal evacuation route.


The surgical evolution of the anal pouch also empowered people who were forced to lose their colon and rectum because of disease with choice: they could decide to live their life with an ileostomy or undergo reconstructive surgery to restore anal evacuation.


Ileo pouch-anal anastomosis (IPAA) surgery is generally viewed as providing benefits over living with an ileostomy from a total proctocolectomy.  However, not all people may consider extra surgery as a 'benefit' and therefore, some people opt to forgo the pouch option and remain living with an ileostomy after disease removal.  Pouches are the individual's choice based on how a person wants to live their life.


After the colon is removed a person does not have the ability to form solid stool.  Because waste will always be liquid, people experience several movements per day when their pouch's capacity is full.  The aim of pouch surgery is 4-8 movements per day, although, some people experience many more.  The number of movements per day may seem similar to when someone was in an  ulcerative colitis  (UC) flare, for people who got their pouch as a result of UC.  People with a small volume pouch will likely experience more movements. [ 115 ]


Additionally, liquid stool directly from the ileum no longer benefits from the colon removing digestive enzymes before a bowel movement.  This means liquid stool produced by the ileum can be aggressive on the skin around the anus.  Discomfort, including experiencing itching and/or burning around the anus' opening, can be treated with creams, by using a squirt water bottle or hand bidet after each movement to wash away enzymes, or by placing a piece of gauze between buttocks to prevent seepage from irritating the skin around the anus. [ 116 ]


The experience of learning how to use a newly functional anal pouch can be distressing for some.  Sharp pains, explosive moments, and anal seepage are common initial sensations.  Specialized pouch centers often have a pouch nurse that educates a person for how to safely empty the pouch without causing avoidable complications like incisional hernias after reversal or takedown surgery. [ 117 ]


The process of adjusting to life with an anal pouch can take many months.  Mayo Clinic research estimates that up to 75% of people with a pouch might experience some level of pelvic floor dysfunction after pouch surgery. [ 118 ]  For pouches that are difficult to evacuate or experience anal seepage, biofeedback therapy can be prescribed. [ 119 ]


Water and salts are typically reabsorbed into the body by the colon or  large intestine .  However, people with an ileum pouch have lost their entire colon and at least small amounts of  ileum .  Experiences like having sudden  diarrhea ,  vomiting  from sickness,  sweating  in hot weather, sweating from  physical exercise , or from not drinking enough  fluids  can all cause dehydration.  Having an episode of pouchitis, or pouch inflammation, can also cause dehydration for some if the episode causes an increase in bowel movements.


This experiences mean that people with pouches, like people with ileostomies, will require drinking more fluids and eating more salt to not become dehydrated.  Dehydration  can cause feelings of  dizziness ,  physical weakness , and/or  fatigue . People may also notice that urine has changed from light yellow and become darker and more concentrated. [ 120 ]


It is important that people with pouches maintain healthy  fluid  and  salt levels  because chronic dehydration increases the risk for  kidney stones  and even  kidney failure .  If a person becomes severely dehydrated, hospital admission for intravenous administration of fluids to restore hydration safely may be required. [ 116 ] [ 121 ]


Many people with a pouch eat their normal diet after surgery while others have to alter their diet due to discomfort when digesting certain foods.  Others experience more watery output after eating specific foods like processed sugary snacks which may require some people with pouches to use dietary or medical interventions like fiber products or doctor prescribed tablets to control watery stool and prevent dehydration. [ 122 ]


People with a pouch can follow any diet they choose while monitoring their overall nutritional status due to the loss of bowel causing absorption issues.  People diagnosed with vitamin or mineral deficiencies may be prescribed injections or tablets.  Others may be referred to a nutritionist to design meals that provide additional amounts of needed vitamins and minerals. Studies show that some foods may also contribute to pouch inflammation. [ 123 ]


Having an intestinal pouch is considered a rare condition.  Some national organizations and specialist charities usually associated with inflammatory bowel disease (IBD) or ostomies provide some information to people considering or who have chosen to undergo elective pouch surgery. Some of the larger national organizations globally include:


Implantable bulking agents  are self-expanding solid  prostheses  which are implanted in the tissues around the  anal canal . [ 1 ]  It is a  surgical treatment for fecal incontinence  and represents a newer evolution of the similar procedure which uses  perianal injectable bulking agents .


The implantable bulking agents represent the most recent stage of development of a similar procedure which uses  perianal injectable bulking agents . That procedure in turn was developed from use of injectable bulking agents in urology to treat  urinary incontinence . Many different injectable materials have been used. The biggest problem with injectable materials is that they seem to have only a temporary effect. Over time, the material degrades and may migrate away from the injection site. For example, one study investigated the outcome and ultrasound appearance of 3 of the commonly used injectable bulking agents (Durasphere, PTQ, Solesta) after an average of 7 years. The researchers reported that typically about 14% of the original volume of material was still identifiable on ultrasound, and that complete disappearance of the materials on ultrasound was correlated with poorer clinical outcomes. [ 3 ]


Implantable bulking agents use multiple cylindrical HYEXPAN ( polyacrylonitrile ) implants. Marketed as "Gatekeeper" by Medtronic, Minneapolis, USA, it was first used to treat  gastro-esophageal reflux disease . [ 1 ]  Production of the implant system was transferred to THD S.p.A., Correggio, Italy. Gatekeeper now has a  CE marking , and was registered for the treatment of fecal incontinence in 2010. [ 4 ]  The first publication describing use of these implants in FI was in 2011. [ 5 ]  Several other publications appeared and the results were initially promising. [ 6 ]


In the original description, Gatekeeper used four self-expandable, solid, thin cylinders. [ 4 ]  Subsequently, six of the prostheses were used. [ 6 ]  An advancement of the procedure was described in 2016, marketed as "SphinKeeper". [ 4 ]  SphinKeeper uses 10 prostheses which are slightly thicker and longer compared to those used in the Gatekeeper implant system. [ 4 ]  One publication stated that new generation SphinKeeper implant system has replaced use of Gatekeeper, and that the use of 10 prostheses represents change in the paradigm of injectable and implantable bulking agents. [ 3 ]  SphinKeeper is a permanent implantable device rather than a bulking agent, and aims to create a kind of artificial neosphincter. [ 3 ]  Previous techniques aimed to simply augment the internal anal sphincter. [ 3 ]  The first systematic review on implantable bulking agents was published in 2022. [ 4 ]  However, no randomized placebo controlled trials have been published yet.


The implants are made of  polyacrylonitrile  (HYEXPAN). This material is inert, non-allergenic, non-immunogenic, nondegradable and noncarcinogenic. [ 1 ]  The material is hydrophilic, which allows the implants to slowly absorb water and change in dimensions, which occurs within 48 hours once they are implanted in the tissues. [ 4 ]


This polyacrylonitrile material is thought to meet the criteria for the "ideal bulking agent", and therefore may overcome the disadvantages of other bulking agents. [ 1 ]


Implantable bulking agents are indicated for passive fecal incontinence, caused by interior anal sphincter dysfunction or damage. [ 1 ]  The onset of incontinence should be at least 6 months ago. [ 6 ]  It has been recommended that this procedure should be attempted only if non-surgical options have failed (such as pharmacologic, behavioral, pelvic floor rehabilitation), [ 6 ]  and also if injectable bulking agents were unsuccessful. [ 1 ]  Researchers are investigating the use of GK and SK in patients with a wider range of causes of fecal incontinence. [ 1 ]


Contraindications have been suggested by different authors, and include:


Diabetes mellitus ,  pudendal neuropathy , and previous implantation of  sacral nerve stimulation  device are not contraindications to the use of implantable bulking agents. [ 6 ]


The procedure is carried out under  local  or regional anesthesia ( Spinal anaesthesia ) with or without  sedation  or  general anesthesia . [ 1 ] [ 6 ] [ 3 ]  It takes 30-40 minutes and may be done as a  day case  on an outpatient basis. [ 1 ]  Intravenous  antibiotics  may given at the start of the procedure. [ 1 ]  The patient is usually put into the  lithotomy position . [ 1 ]


The surgeon identifies the interior anal sphincter and the intersphincteric groove while using an anal retractor such as the Eisenhammer retractor. 2 cm away from the anal verge a 2 mm incision is made in the perianal skin. [ 1 ]  This location may minimize the possibility of contamination of the wounds during bowel movements. [ 6 ]  The prostheses are implanted using a custom "gun" which consists of a delivery system and a dispenser which holds one prosthesis at a time. [ 1 ]  This device is specific to the type of implant being used: Gatekeeper or SphinKeeper. [ 6 ]  The needle (cannula / sheath) is inserted into the incision and pushed into the intersphincteric space through a short subcutaneous tunnel. [ 1 ] [ 6 ]  It is thought that the path of this created "tunnel" should not be a straight line, in order to prevent extrusion of the prosthesis along the insertion track. [ 6 ]  The needle is advanced to a depth just beyond the level of the  dentate line . [ 1 ]  This will correspond to the upper part of the anal canal, at the level of the  puborectalis muscle . [ 6 ]  The exact position of the needle tip is confirmed by direct vision or with the guidance of endoanal ultrasound. [ 1 ]  The procedure is described as relatively simple to perform from a technical perspective, [ 4 ]  and one author stated that ultrasound guidance during placement is not necessary if the surgeon is experienced. Firing the "gun" causes the cannula to retract completely into the delivery system, leaving the prosthesis in the target location. [ 6 ]  The prosthesis is then placed into the intersphincteric space. [ 1 ]


It is thought that placement of the implants in the intersphincteric space pushes the external anal sphincter outwards and the internal anal sphincter inwards. This may increase the length of the  sarcomeres , which theoretically increases the contractility of the muscle. In terms of physiological measurements, the resting anal pressure and the length of the high pressure zone in the anal canal may be improved. In other words, the bulking effect may improve the seal of the anal canal and the length of the anal canal. [ 1 ]


The surgical procedure is almost identical for Gatekeeper and SphinKeeper. The difference between Gatekeeper and SphinKeeper is in the size and number of the individual prostheses. Gatekeeper uses 4-6 prostheses. SphinKeeper uses up to 10 prostheses. [ 1 ]


Within 48 hours of implantation, the implant material absorbs water from the tissues because of its hydrophilic properties. Each prosthesis becomes thicker and shorter in shape. This rapid increase in volume allows the prostheses to self-fix in position and prevents displacement and migration (in most cases). [ 1 ]  The prostheses also become softer in consistency and compliant to external pressures, but are still able to maintain their original shape. [ 6 ]


In the dehydrated state, Gatekeeper prostheses are thin cylinders, 2 mm in diameter and 22 mm long. After implantation, they become 6.5 mm in diameter and 17 mm long. Their volume increases by 750% from 70 mm 3  to 500 mm 3 . [ 1 ]


SphinKeeper prostheses are slightly thicker and longer cylinders. In the dehydrated state, SphinKeeper prostheses are 3 mm in diameter and 29 mm long. After implantation, they become 7 mm in diameter and 23 mm long. [ 1 ]  SphinKeeper implants are long enough to restore the normal length of the anal canal. [ 6 ]  They are also wide enough to make sure there is good filling ability. Therefore, SphinKeeper allows for surgical correction of larger defects of the internal anal sphincter or external anal sphincter. [ 6 ]


The process is repeated for each individual prosthesis, placing them into incisions made at the intersphincteric groove at equidistant intervals depending upon the total number of prostheses to be deployed. [ 1 ]  For example, if 4 prostheses are to be used, incisions may be placed at 12, 3, 6, and 9 o’clock. If 6 prostheses are to be used, incisions may be placed at 1, 3, 5, 7, 9, and 11 o’clock. [ 6 ]  The exact number of prostheses used is arbitrary, but placing 10 prostheses enables the creation of a circumferential ring of prostheses around the anal canal in the intersphincteric space. This effectively creates a situation similar to an artificial anal sphincter. [ 1 ]  One publication reported improved outcome with Gatekeeper when more prostheses were used. [ 6 ]


Interestingly, it is thought that the exact spacing of the prostheses does not influence the outcome of the procedure, and the important factor appears to be that the prostheses are distributed equally around the anal canal. [ 6 ]  This is the case even in the presence of tears of the external anal sphincter or internal anal sphincter. [ 6 ]  Therefore, the implants are placed in the above locations for convenience of the surgeon, even for patients with a tear in a specific part of the sphincter. [ 6 ]


The incisions are closed with resorbable sutures. Endoanal ultrasound may be used to confirm the location of each prosthesis. A course of oral antibiotics (e.g. metronidazole) may be given after the procedure. Oral  laxatives  (e.g.  lactulose ) may be given, which prevents straining and constipation. Anal trauma (e.g. receptive anal intercourse) should be avoided for at least 72 hours after the procedure. [ 1 ]  Patients are usually advised to rest in bed, with the aim of reducing the risk of dislocation of the prostheses. [ 6 ]


After healing, the implants continue to be palpable and are visible on endoanal ultrasound. [ 1 ]  Each prosthesis appears as hyperechoic dot with a hypoechoic shadow behind it. [ 6 ]  Three dimensional endoanal ultrasound has also been used to visualize the implants, wherein the prostheses appear as a continuous hyperechoic line. [ 6 ]


Compared to other surgical treatment options for fecal incontinence, implantable bulking agents appear to be safe. [ 6 ]  Therefore, it is also suitable for elderly or frail patients. [ 6 ]  However, complications are sometimes reported. For example, acute sepsis (infection) at the implantation site has been rarely recorded. [ 6 ]


The most important complication is displacement of a prosthesis (also referred to as migration / dislocation / dislodgement / extrusion). [ 6 ]  The rate of displacement of at least 1 of the prostheses has been reported to be as low as 0%, or as high as 91% of cases. [ 4 ]  The patient may report pain, swelling and/or no improvement in symptoms when there is prosthesis displacement. [ 6 ]  This is potentially noteworthy, [ 7 ]  since improved symptoms after use of injectable bulking agents have been attributed at least in part to the  placebo effect . [ 8 ]


Placement in the intersphincteric space is thought to be less liable to extrusion or migration of the prostheses or other complications such as erosion, ulceration or fistula formation in the anal canal. [ 1 ] [ 6 ]  If the implants were in the submucosal layer, they would be more vulnerable to such complications. [ 1 ]  Furthermore, displacement is less likely because of the rapid increase in size of the prostheses, [ 4 ]  allowing them self-fix in position in most cases. [ 1 ]


A systematic review found that in total, migration / dislodgement / dislocation was reported in 41 out of 154 patients (26.6%) across 7 studies. [ 4 ]  The same researchers reported that some kind of adverse event occurred in 48 out of 166 patients (28.9%). [ 4 ]  Sometimes, a prosthesis had to be removed, [ 4 ]  however it is possible to implant a new one in the correct position. [ 6 ]


The first systematic review on GK and SK was published in 2022. It combined results from 8 studies published before 2020 – a total of 166 patients. All studies were judged to be at moderate to high risk of bias. The reviewers reported that severity of FI improved in 5 out of 7 of the studies which used the Cleveland Clinic FI Score and in 3 out of 5 of the studies which used the Vaizey score. Quality of life improved in 2 studies which measured that outcome. They concluded that GK and SK may be effective, safe and minimally invasive options for fecal incontinence in those cases where non surgical treatments have failed. The reviewers called for controlled trials to be conducted. [ 4 ]


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Intestine transplantation  ( intestinal transplantation,  or  small bowel transplantation ) is the  surgical   replacement  of the  small intestine  for  chronic  and  acute  cases of intestinal  failure . While intestinal failure can oftentimes be treated with alternative therapies such as  parenteral nutrition  (PN), complications such as PN-associated  liver disease  and  short bowel syndrome  may make transplantation the only viable option. One of the rarest type of  organ  transplantation performed, intestine transplantation is becoming increasingly prevalent as a therapeutic option due to improvements in  immunosuppressive regimens , surgical technique, PN, and the clinical management of pre and post-transplant patients. [ citation needed ]


Intestine transplantation dates back to 1959, when a team of surgeons at the  University of Minnesota  led by Richard C. Lillehei reported successful transplantation of the small intestine in dogs. Five years later in 1964, Ralph Deterling in  Boston  attempted the first human intestinal transplant, albeit unsuccessfully. For the next two decades, attempts at transplanting the small intestine in humans were met with universal failure, and patients died of technical complications,  sepsis , or  graft rejection . However, the discovery of the immunosuppressant  ciclosporin  in 1972 triggered a revolution in the field of transplant medicine. Due to this discovery, in 1988, the first successful intestinal transplant was performed in Germany by E. Deltz, followed shortly by teams in France and Canada. Intestinal transplantation was no longer an experimental procedure, but rather a life-saving therapy. In 1990, a newer immunosuppressant drug,  tacrolimus , appeared on the market as a superior alternative to ciclosporin. In the two decades since, intestine transplant efforts have improved tremendously in both number and outcomes. [ 1 ] [ 2 ]


Failure of the small intestine is life-threatening due to the inability to absorb  nutrients ,  fluids , and  electrolytes  from food. Without these essential substances and the ability to maintain  energy balances ,  homeostasis  cannot be maintained and one's  prognosis  will be dismal. Causes of intestinal failure may be clinically complex, and may result from a combination of nutritional,  infectious ,  traumatic , and  metabolic  complications that affect ordinary  anatomy  and  physiology . [ 3 ]  Many underlying conditions that serve as precursors to failure are genetic or congenital in nature. For example, severe  inflammation ,  ulceration ,  bowel obstruction ,  fistulation ,  perforation , or other pathologies of  Crohn's disease  may severely compromise intestinal function. [ 4 ]  Despite the danger these conditions may pose in themselves, they may lead to even further, more serious complications that necessitate replacement of the diseased intestine. The single leading cause for an intestinal transplant is affliction with  short bowel syndrome , oftentimes a secondary condition of some other form of intestinal disease. [ 5 ] [ 6 ]  Short-bowel syndrome was the cause for 73% of American intestinal transplantations in 2008, followed by functional bowel problems for 15% and other causes representing 12% of cases. [ 7 ]  Natural SBS is mercifully rare, estimated to be 3 per 100,000 births. [ 8 ]  Surgical removal is the most common cause, performed as a treatment for various  gastroenterological  and  congenital  conditions such as Crohn's disease,  necrotizing enterocolitis ,  mesenteric ischemia ,  motility disorder ,  omphalocele / gastroschisis ,  tumors , and  volvulus . [ 9 ]


Regardless of the underlying condition, the loss of intestinal function does not necessarily necessitate a transplant. Several conditions, such as necrotizing enterocolitis or volvulus, may be adequately resolved by other surgical and nonsurgical treatments, especially if SBS never develops. An individual can obtain nutrients intravenously through PN, bypassing food consumption entirely and its subsequent  digestion . Long-term survival with SBS and without PN is possible with  enteral nutrition , but this is inadequate for many patients as it depends on the remaining intestine's ability to adapt and increase its absorptive capacity. [ 3 ]  Although more complicated and expensive to perform, any person may receive PN. Although PN can meet all energy, fluid, and nutrient needs and can be performed at home,  quality of life  can be significantly decreased. On average, PN takes 10 to 16 hours to administer but can take up to 24. Over this time frame, daily life can be significantly hindered as a consequence of attachment to the  IV pump . [ 5 ] [ 10 ]  Over long periods of time, PN can lead to numerous health conditions, including severe  dehydration ,  catheter -related infections, and liver disease. [ 2 ] [ 11 ]  PN-associated liver disease strikes up to 50% of patients within 5–7 years, correlated with a mortality rate of 2–50%. [ 11 ]


Another alternative treatment to transplant for patients with SBS is surgical bowel lengthening via either  serial transverse enteroplasty  (STEP) or the older  longitudinal intestinal lengthening and tailoring  (LILT) technique. Although both procedures contribute to an approximate 70% increase in length, STEP appears somewhat more favorable in terms of lower mortality and progression to transplant. [ 12 ]  Nevertheless, a positive reception to either procedure may reduce the level of PN required, if not negate its required use altogether. [ 8 ] [ 13 ]


There are four  Medicare  and  Medicaid -approved  indications  for intestine transplantation: a loss of two of the six major routes of  venous access , multiple episodes of  catheter -associated life-threatening sepsis, fluid and electrolyte abnormalities in the face of maximal medical therapy, and PN-associated liver disease. Transplants may also be performed if the growth and development of a  pediatric  patient fails to ensue, or in extreme circumstances for patients with an exceptionally low quality of life on PN. [ 14 ] [ 15 ]  A multidisciplinary team consisting of  transplant surgeons ,  gastroenterologists ,  dieticians ,  anesthesiologists ,  psychiatrists , financial representatives, and other  specialists  should be consulted to evaluate the treatment plan and ensure transplantation is the patient's best option.  Psychological  preparations should be made for the transplant team and patient as well. Early referral requires trust between all parties involved in the operation to ensure that a rush to judgment does not lead to a premature transplant. [ 11 ] [ 16 ]


Other  absolute contraindications  to receiving an intestinal transplant include the presence of  systemic  and untreated local infections, malignant cancer, severe  neurological impairment , and severe  cardiac  and/or  pulmonary disease .  These criteria are similar to established guidelines for transplants of other organ types. [ 17 ]  HIV infection is a  relative contraindication  for intestine transplantation; desperate terminal patients may accept a transplant from a HIV-positive donor if they are willing to expose themselves to HIV. [ 14 ]


There are three major types of intestine transplants: an isolated intestinal  graft , a combined intestinal-liver graft, and a  multivisceral graft  in which other  abdominal  organs may be transplanted as well. In the most basic and common graft, an isolated intestinal graft, only sections of the  jejunum  and  ileum  are transplanted. [ 18 ]  These are performed in the absence of liver failure. In the event of severe liver dysfunction due to PN,  enzyme  deficiencies, or other underlying factors, the liver may be transplanted along with the intestine. In a multivisceral graft, the  stomach ,  duodenum ,  pancreas , and/or  colon  may be included in the graft. Multivisceral grafts are considered when the underlying condition significantly compromises other sections of the digestive system, such as intra-abdominal tumors that have not yet  metastasized , extensive venous  thrombosis  or  arterial   ischemia  of the  mesentery , and motility syndromes. [ 11 ] [ 17 ]


Donated  intestines, like all organs, should be matched to a recipient prior to recovery, as to prepare him or her and minimize the time the organ spends outside the  body . [ 5 ]  Potential recipients are placed on the  International Intestinal Transplant Registry  (ITR), where they contribute to the world's growing understanding of intestine transplantation. Before a transplant may be performed, an organ must first be located. In the United States, the matching of all organs is coordinated by the  United Network for Organ Sharing  (UNOS). The standard intestinal donor is deceased with a diagnosis of  brain death . [ 19 ]  In terms of transplant outcomes, brain-dead donors are highly preferable to donors who have suffered  cardiopulmonary death . If respiration can be assisted by a  ventilator , brain-dead donors may exhibit maintainable  cardiac ,  endocrine , and  excretory  function. If appropriately managed, the continuation of  blood flow  and bodily metabolism allows for healthier organs for procurement and additional time to prepare recipients for transplant. [ 20 ]  Furthermore, terminal ileum recovery from living donors is possible., [ 21 ]  and a  laparoscopic technique  is being developed to harvest limited sections of small bowel from living donors. [ 22 ]  When determining potential donor-recipient matches, important characteristics include donor size, age,  tissue  quality, and  ABO  and  histo-compatibility . [ 11 ] [ 21 ]  If the intestine is too large, it may be not transplantable into young or small patients. Ideally, intestines should be selected from donors of lighter weight than the proposed recipients to ensure simple closure of the abdominal wound. [ 23 ]  If a patient is too young or too old, they may not be hardy enough to survive the operation and recovery period. [ 11 ]  If the donor and recipient organs do not meet compatibility requirements, the threat of  organ rejection  by the body is all but certain.


Organ rejection is the unfortunate circumstance of the host  immune system  recognizing the transplanted organ as foreign. This is the most notable complication facing transplant recipients. Through  T-cell receptors ,  T-lymphocytes  are able to distinguish between self and non-self by recognizing  human leukocyte antigens  (HLA) bound to the  major histocompatibility complex  (MHC)  protein  located on the surface of organ  cells . Once identified as foreign, the immune system proceeds to destroy the transplanted tissue. The  panel-reactive antibody  (PRA) test measures the proportion of the population to which a recipient will react via pre-existing  antibodies  to various HLA  antigens ; in other words, how likely a patient is to acutely reject their new transplant. Therefore, it is essential that HLA and PRA statuses are tested for and demonstrate low immunoreactivity of the patient to the graft. [ 2 ] [ 21 ] [ 24 ]  In some cases, a recipient may suffer from  graft-versus-host disease , in which cells of the transplanted organ attack the recipient's cells. [ 25 ]


To ensure proper histocompatibility, tissue quality, and safety from infection,  blood work  should be collected and tested in the laboratory. In addition to HLA and PRA typing, the  complete blood count  (CBC),  coagulation  profile,  complete metabolic panel , and  ABO blood group  determination tests should be performed for both the donor and recipient. [ 2 ]  ABO-incompatible grafts can sometimes be performed on very young pediatric patients, as their immune systems have not fully developed and for whom waiting list mortality remains high. [ 14 ]  Additionally, blood  serum  should be  tested  for the presence of  viruses , including HIV,  hepatitis B  and  C ,  cytomegalovirus  (CMV), and  Epstein–Barr virus  (EBV) antibodies to prevent infection. [ 24 ]  Particularly in the immunocompromised system necessitated by the transplant, these viruses can wreak havoc on the body and become extremely dangerous, even fatal. Even with healthy physiological levels, ABO and HLA compatibilities, and no signs of bacterial, viral, and  fungal  infections, organ transplantation is not without extrasurgical risk. [ 2 ]


A major challenge facing the intestinal transplant enterprise is meeting the need for transplantable intestines, particularly in the United States where the majority of intestinal transplants take place. [ 9 ]  There exists a narrow timeslot between procurement and transplantation that any organ remains viable, and logistical challenges are faced regarding bringing organ and recipient together. During procurement, organs that are being recovered are cooled and  perfused  with preservation solution. This slows organ activity and increases the time they remain viable for transplant. [ 2 ]  Although chilling and perfusion may extend intestinal lifespans by several hours, failure is still imminent unless transplanted. This duration between the cooling of the organ during procurement and the restoration of physiological temperature during implantation is the  cold ischemic time . Due to the sensitivity of the intestine to ischemic injury, many potential donor intestines are lost to the events following brain death and trauma. Furthermore, irreversible intestinal damage is seen after approximately only 5 hours of cold ischemia in the form of  mucosal  damage and bacterial translocation outside the  gastrointestinal tract . Therefore, ensuring cardiac survival and nearby donor-recipient proximity before procurement are essential so organs do not wait too long outside the body and without blood flow. [ 11 ]  Not only is there a lack of transplantable intestines, but a deficiency in the number of centers possessing the capability to carry out the complicated transplant procedure as well. As of 2005 [update] , there were only 61 medical centers in the world capable of executing an intestinal transplant. [ 9 ]  Furthermore, many young, small children, particularly those weighing less than 5  kg , cannot find a transplant due to the lack of size-matched donors. [ 8 ]


Despite these challenges, obtaining an intestine for transplant is rather probable in the United States. In 2008, there were 212 people on the U.S. intestinal transplant waitlist, 94% of whom were U.S. citizens. [ 7 ]  Regardless of transplant type, over half of new registrants are 5 years of age or younger.  Adults  compromise the next largest cohort, followed by pediatric patients aged 6 and older. In 2008, the  ethnic  composition of the intestinal transplant waitlist was 65%  White , 18%  Black , 16%  Hispanic , 1%  Asian , and 0.5% other or  mixed race , resembling the  demographics  of the American general population at the time aside from a below-average Asian cohort. ABO blood types also matched the general population, with 31% A, 14% B, 5% AB, and 50% O. [ 7 ]  In 2004, the average waiting period to receive a transplant was 220 days, [ 21 ]  with a  median  of 142 days in 2008. [ 7 ]  The rate of waitlist additions has shifted from year to year; gains increased until 2006 (with 317 added), but then decreased in 2012 (to 124 added). [ 26 ]  In 2007, only 9% of patients on the U.S. waitlist died while waiting for a transplant. [ 7 ]  Waitlist mortality peaked around 2002 and was highest for liver-intestine (pediatric) patients. Deaths among all pediatric groups awaiting intestine-liver transplants have decreased in the years leading up to 2014 whereas adult intestine-liver deaths have dropped less dramatically. The decrease in recent years is likely due to improved care of infants with intestinal failure and subsequently a decrease in referrals for transplant. [ 26 ]  Although many improvements have been made in the States, outcomes everywhere still demonstrate much room for improvement. Worldwide, 25% of pediatric patients on the waitlist for an intestinal transplant die before they can receive one. [ 8 ]


Following matching of the organ, the complicated procurement of the small bowel can be performed by a team of abdominal transplant surgeons. Once a donor has been selected and approved for donation, several pretreatments may be initiated to destroy  microorganisms  and  immune cells . The donor intestine must be  decontaminated  with several  antibiotics , including  neomycin ,  erythromycin ,  amphotericin B , and  cephalosporin . [ 18 ]  They may also be treated with anti- lymphocyte  antibodies ( anti-thymocyte globulin ,  alemtuzumab ),  irradiation  directed against excessive mesenteric  lymphatic tissue , and have their bowel  irrigated . [ 17 ]


Once donor preparation is accomplished, procurement can begin by utilizing the same standard techniques for all abdominal organ procurements. The team exposes the abdominal cavity and inserts two  cannulae  for the  infusion  of  University of Wisconsin   organ preservation solution  into the  aorta  and  inferior mesenteric vein . As the abdominal organs are cooled  in situ , the surrounding tissue is  dissected  so that they may be quickly extracted. In the next step, the aorta is  cross-clamped , cutting off blood supply to the organs. Once blood and oxygen supply to an organ is cut off, organ death will approach swiftly unless steps are taken to preserve them until transplant. Organs are therefore fully  drained of blood , flushed with cool preservation solution, and removed from the body. [ 2 ] [ 18 ]  In an isolated intestinal transplant, the  colon will be detached  from the small intestine. The  cecum  and  ascending colon  are devascularized, while care is taken to preserve major  vasculature  in the ileum. The jejunum will be separated from the duodenum while preserving the vasculature of the jejunum, ileum, mesentery, and the pancreas. If healthy, the pancreas can oftentimes be retrieved as an additional isolated procurement. The intestinal allograft, when ready to be extracted, is attached by the mesenteric  pedicle , where the vessels converge out of the intestinal system. This pedicle will be  stapled  closed, and can be separated from the body via a  transverse  cut to create a vascular cuff. The complete intestinal allograft can then be removed and wrapped in a surgical  towel . [ 18 ]  The protocols for combined liver and multivisceral procurements are far more complicated and meticulous than isolated intestine alone. [ citation needed ]


First, any abdominal  scar tissue  from previous surgeries must be removed. The aorta and  vena cava  are dissected in preparation for vascular  anastomosis , followed by dissection of the  proximal  and  distal  ends of the digestive tract. Anastomosis is then performed to revascularize the graft. Arterial vessels are connected to the abdominal aorta, below the  kidneys . However, venous drainage, or the reattachment of the transplanted organ to the venous system, may be performed differently depending on the unique intra-abdominal vasculature of the recipient. The graft is usually drained systemically into the  infrarenal  vena cava, [ 15 ]  but may also be drained  portally  into the  hepatic portal  or  superior mesenteric vein . [ 17 ]  The graft is then reperfused with blood and any bleeding is stopped before the proximal and distal ends of the transplant bowel are connected to the original digestive tract. A loop  ileostomy  is then created as to provide easy access for future  endoscopic  observation and  biopsies . A  gastronomy  or  jejunostomy   feeding tube  may be placed before the abdominal wall is closed. [ 2 ]


When a liver is being transplanted in conjunction with the intestine, the recipient must first have their own  liver removed . Following this, the aorta, cava, and portal veins of the donor and recipient are anastomosed. The graft is then flushed before the caval  clamps  are removed. The intestine is then reconstructed as in an isolated intestinal transplant, before being connected to the  bile duct  servicing the new liver. [ 17 ]   Multivisceral transplants  are especially difficult and susceptible to complications because all organs must survive a conjoined procurement, transport, and transplantation. All three of these measures are tailored to the individual needs of the recipient. [ 18 ]  Preservation of the native  spleen , pancreas, and duodenum during a multivisceral transplant can reduce the risk of additional complications related to these structures. [ 11 ]


Following the procedure, the patient is actively monitored in an  intensive care unit  (ICU).  Broad-spectrum antibiotics  are administered, bleeding monitored, and serum  pH  and  lactate  levels measured for evidence of intestinal ischemia. The patient's immune system is strongly modulated immediately post-operation. The  initial phase of treatment  consists of the administration of tacrolimus with  corticosteroids  to suppress T-lymphocyte activation. Next, various assortments of  interleukin-2  (IL-2)  receptor   antagonists  ( daclizumab ,  basiliximab ), anti-proliferation agents ( azathioprine ,  mycophenolate mofetil ), and the drugs  cyclophosphamide  and  sirolimus  are administered on an individual patient basis to further suppress the immune system. [ 11 ]  The  bioavailability  of these drugs is dependent on intestinal  surface area  and transit time, and therefore the length of the allograft determines the immunosuppression regimen. [ 2 ]  Intravenous administration of  prostaglandin E1  is occasionally performed for the first 5 to 10 days following transplant to improve intestinal circulation and a potential dispensing of immunosuppressive effects. [ 2 ] [ 11 ]  The gut is selectively decontaminated against high-risk  flora  and  preventative care  is taken against CMV and fungal infections. [ 11 ]


It is ideal to commence enteral nutrition as early as possible following transplantation. Therefore, a feeding tube connecting to the stomach or jejunum is quickly placed to facilitate rehabilitation. [ 11 ]  If gastrointestinal function is restored, a diet can be reestablished and cautiously advanced as tolerated. Most patients are weaned from PN within 4 weeks of transplantation, and nearly all are free from additional enteral supplementation by one year. [ 14 ]  Evidence for the restoration of function includes decreasing gastrostomy tube returns and increasing  gas  and enteric contents in the ileostomy. [ 2 ]  Routine surveillance endoscopy and biopsies via the ileostomy should be performed with decreasing frequency over several months to observe signs of rejection, ideally before clinical symptoms present themselves. Should the patient continue to perform well through the first post-transplant year, the ileostomy would generally be closed. Should rejection be suspected in the future, endoscopies would be performed and an appropriate antirejection therapy will be tailored. The median time for hospital  discharge  varies between procedures. The median times for isolated intestine, intestine-liver, and multivisceral transplants are 30, 60, and 40 days post-operation respectively. [ 14 ]  Within the first several months,  carbohydrate  and  amino acid  absorptive capacity should normalize, followed by the absorptive capacity for fats. Once enteral nutrition is capable of providing all nutritional needs, PN can be discontinued. [ 2 ]  Nearly all patients with a successful transplant are free of PN within one year. [ 14 ]


Intestinal transplantation is the least performed type of transplant due to a number of unique obstacles. The most major of these is the profound immunosuppression required due to the ability of the intestine to elicit strong immune responses. Because of exposure to a wide range of gut flora and material consumed by the body, the intestinal  epithelium  possesses a highly developed  innate immune system  and  antigen-presenting  abilities. Immunosuppression is the primary determinant of outcome in small bowel transplantation; the risk for graft rejection is increased by under-immunosuppression and for local and systemic infection with over-immunosuppression. [ 11 ]  Ensuring an appropriate dose of immunosuppressant can therefore be difficult, especially as both ciclosporin (14–36%) and tacrolimus (8.5–22%) have generally low bioavailabilities. [ 27 ]  A major problem due to immunosuppression in intestinal transplant patients is post-transplant  lymphoproliferative disorder , in which B-lymphocytes excessively proliferate due to infection by EBV and result in infectious  mononucleosis -like lesions. [ 7 ]  Intestinal transplant recipients are also at risk for chronic  renal failure  because  calcineurin  inhibitors are  toxic  to the kidneys. A transplant recipient must remain on immunosuppressants for the rest of his or her life. [ 14 ]


Intestinal transplants are highly susceptible to infection even more so than the standard immunocompromised recipient of other organs due to the great composition and variety of the gut flora. [ 11 ]  A complex assortment of microorganisms inhabits the human digestive tract, with concentrations of up to 10 4 –10 7   CFU /mL in the jejunoileum and 10 11 –10 12  CFU/mL in the colon. [ 28 ]  While suppression of the immune system may prevent immune attack on the new allograft, it may also prevent the immune system's ability to keep certain gut microbial populations in line. Despite pre and post-decontamination of the transplant, recipients are at risk of local and systemic infection by both natural and external flora. The common symptom of graft dysfunction, whether due to infection, rejection, or some other condition, is  diarrhea . [ 15 ]


Intestinal transplant outcomes have improved significantly in recent years. Despite mild incongruities in survival rate percentages between centers in North America, Europe, Australia, and elsewhere, intestinal transplantations mostly approach survivorship rates of  lung transplantation . [ 11 ]  At one-year, graft survival rates for isolated intestine currently waver around 80%, and 70% for intestine-liver and multivisceral. Over the same time period, patient survival for isolated intestine patients may even exceed 90%, while the more complicated multiorgan transplants do not show any increase in patient survival when compared to patients surviving with the intestinal graft alone. [ 14 ]  The five-year survival rate for patients and transplants ranges from 50 to 80% (overall mean 60%), depending on underlying disease and presurgical  morbidity . Very young (<1 year) and very old (>60 years) patients receiving a transplant have pronounced rates of mortality. [ 14 ] [ 15 ]  After 4 years, pediatric survival significantly worsens compared to adults. [ 14 ]