MEITL is thought to arise from  intraepithelial lymphocytes  that normally reside in the  epithelial  lining of the GI tract and over time acquire abnormalities that promote their survival, proliferation,  avoidance of the  immune system , and thereby malignancy. These cells are not infected with the Epstein-Barr virus and therefore have not become malignant as a consequence of this  virus's malignancy-producing  effects on lymphocytes as it does in other types of GI tract lymphomas. Rather, the malignant T cells in MEITL bear various genetic abnormalities that may promote their malignancy.  Restriction fragment length polymorphism  studies indicate that these cells have abnormal gains in  minisatellites , i.e. repetitive small DNA sequences, in  chromosomes  1, 5, 7, 8, 9, 13, 16, and 18. These minisatellites disrupt the production of some genes but the potential relevancies of these disruptions have not been defined. [ 4 ]   Genetic abnormalities commonly found in MEITL that do have potentially pro-malignant effects include:


Further studies are required to determine which, if any, of these genetic abnormalities play a role in the development and/or progression of MEITL and therefore are therapeutic targets for treating the disease. [ 4 ]


The symptoms of MEITL are generally non-specific. The diagnosis depends on  endoscopic  findings in the GI tract, histological findings on biopsied specimens from involved areas of the GI tract, evidence of disease involvement outside of the GI tract, and the differentiation of MEITL from other GI tract lymphomas and benign lymphoproliferative diseases. Endoscopy typically shows multiple raised and/or ulcerated lesions involving the  jejunum  or  ileum , and less commonly, the  duodenum ,  stomach , or  colon . [ 3 ]  These lesions may occur at multiple sites or spread throughout large areas of the GI tract. Biopsied tissues show abnormally broad  intestinal villi  caused by the infiltration of sheets of uniformly-sized lymphocytes. These lymphocytes may also infiltrate and disrupt the architecture of nearby  intestinal crypts  and the  epithelial lining . Unlike celiac disease-associated EATL, the lesions usually have little evidence of inflammatory cells (particularly lymphoplasmacytoid cells, i.e. cells showing a mixture of  B cell  and  plasma cell   morphological  features) or of infiltration of the epithelium lining by the types of lymphocytes seen in celiac disease. [ 2 ]  The lymphocytes in these lesions are T cells expressing the marker molecules and genetic abnormalities given in the above Pathophysiology section. [ 3 ] [ 4 ] [ 8 ]   CT scans  commonly reveal involvement of  mesenteric lymph nodes . [ 2 ]  Advanced cases have involvement of the  bone marrow [ 5 ]  and/or dissemination into other organs. [ 9 ]


MEITL must be  differentiated  from the following GI tract disorders with which it shares some common features.


There is no standard treatment for MEITL. Most individuals have been treated by surgical resections of involved areas with or without  anthracycline -based  chemotherapy . In these cases, responses have been short-lived and/or poor with 1 year overall survival rates, 1 year progression free survival rates, and median survival times of 36%, 21%, and 7 months, respectively. [ 5 ]  A retrospective study of patients treated with resection, chemotherapy and  autologous hematopoietic stem cell transplantation  had a higher 1-year and 5-year overall survival (100%, 33%) compared to one-year survival (73%) and five-year survival (14%) without transplantation; a second retrospective study supported the usefulness of transplantation in that high-dose lymphoma chemotherapy followed by transplantation and standard-dose lymphoma chemotherapy with or without surgical resection increased 5-year overall survival from 22 to 60% and 5-year disease progression-free survival from 22 to 52%. [ 13 ]  While further studies, particularly  randomized controlled trials , are needed to investigate the best treatments for MEITL, the use of lymphoma chemotherapy, hematopoietic stem cell transplantation, and, where needed, surgical resections are the currently recommended treatments for MEITL. [ 3 ]


Mucositis  is the painful  inflammation  and  ulceration  of the  mucous membranes  lining the  digestive tract , usually as an adverse effect of   chemotherapy  and  radiotherapy  treatment for cancer. [ 1 ]  Mucositis can occur anywhere along the gastrointestinal (GI) tract, but  oral mucositis  refers to the particular inflammation and ulceration that occurs in the mouth. [ 2 ]  Oral mucositis is a common and often debilitating complication of cancer treatment. [ 3 ]


Oral and gastrointestinal (GI) mucositis affects almost all patients undergoing high-dose chemotherapy and  hematopoietic stem cell transplantation  (HSCT), 80% of patients with  cancers of the head and neck  receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary tract mucositis increases mortality and morbidity and contributes to rising health care costs. [ 4 ]


For most cancer treatment, about 5–15% of patients get mucositis. However, with 5- fluorouracil  (5-FU), up to 40% get mucositis, and 10–15% get grade 3–4 oral mucositis. [ 4 ]   Irinotecan  is associated with severe GI mucositis in over 20% of patients. Seventy-five to eighty percent of bone marrow transplantation recipients experience mucositis, of which oral mucositis is the most common and most debilitating, especially when melphalan is used. In grade 3 oral mucositis, the patient is unable to eat solid food, and in grade 4, the patient is unable to consume liquids as well. [ 4 ]


Radiotherapy to the head and neck or to the pelvis or abdomen is associated with Grade 3 and Grade 4 oral or GI mucositis, respectively, often exceeding 50% of patients. Among patients undergoing head and neck radiotherapy, pain and decreased oral function may persist long after the conclusion of therapy. Fractionated radiation dosage increases the risk of mucositis to > 70% of patients in most trials. Oral mucositis is particularly profound and prolonged among  HSCT  recipients who receive total-body irradiation. [ 4 ]


Oral cancer  patients undergoing chemotherapy usually become symptomatic four to five days after beginning treatment, reaching a peak at around day 10, and then slowly improving over the course of a few weeks. Mucositis associated with radiotherapy usually appears at the end of the second week of treatment and may last for six to eight weeks. [ citation needed ]


As a result of cell death in reaction to chemo- or radio-therapy, the mucosal lining of the mouth becomes thin, may slough off and then become red, inflamed and ulcerated. The ulcers may become covered by a yellowish-white fibrin clot called a pseudomembrane. Peripheral  erythema  is usually present. Ulcers may range from 0.5 cm to greater than 4 cm. Oral mucositis can be severely painful.  The degree of pain is usually related to the extent of the tissue damage.  Pain is often described as a burning sensation accompanied by reddening. Due to pain, the patient may experience trouble speaking, eating, or even opening the mouth. [ citation needed ]


Dysgeusia , or an alteration in taste perception, is common, especially for those who are receiving concomitant radiation therapy to the neck and mouth area. "Taste blindness", or an altered sense of taste, is a temporary condition that occurs because of effects on taste buds that are mostly located in the tongue. Sometimes, only partial recovery of taste occurs. Common complaints are of food tasting too sweet or too bitter or of a continuous metallic taste. [ citation needed ]


Sores or ulcerations can become infected by  virus ,  bacteria  or  fungus . Pain and loss of taste perception makes it more difficult to eat, which leads to weight loss. Ulcers may act as a site for local infection and a portal of entry for oral flora that, in some instances, may cause  septicaemia  (especially in immunosuppressed patients). Therefore, oral mucositis can be a dose-limiting condition, disrupting a patient’s optimal cancer treatment plan and consequentially decreasing their chances of survival. [ 5 ]


The  pathophysiology  of mucositis is complex and multifactorial. Currently, Sonis' five phase model is the accepted explanation for the process. [ 5 ] [ 6 ]  The 5 stages are:


Diagnosis is based on the symptoms the patient is experiencing and the appearance of the tissues of the mouth following  chemotherapy ,  bone marrow  transplants or  radiotherapy . Red burn-like sores or ulcers throughout the mouth is enough to diagnose mucositis. [ citation needed ]


The severity of oral mucositis can be evaluated using several different assessment tools.
Two of the most commonly used are the World Health Organization (WHO) Oral Toxicity score [ 9 ]  and the National Cancer Institute Common Toxicity Criteria (NCI-CTC) for Oral Mucositis. [ 10 ]  While the NCI system has separate scores for appearance (erythema and ulceration) and function (pain and ability to eat solids, liquids, or nothing by mouth), the WHO score combines both elements into a single score that grades the severity of the condition from 0 (no oral mucositis) to 4 (swallowing not possible such that patient needs supplementary nutrition). Another scale developed in 1999, the Oral Mucositis Assessment Scale (OMAS) has been shown to be highly reproducible between observers, responsive over time, and accurate in recording symptoms associated with mucositis.   The OMAS provides an objective assessment of oral mucositis based on assessment of the appearance and extent of redness and ulceration in various areas of the mouth. [ 11 ]


A 2015 Cochrane systematic review assessing the prevention of chemotherapy-induced oral mucositis concluded that oral cryotherapy leads to large reductions in the incidence of oral mucositis of all severities in adults receiving  5-FU  treatment for solid cancers. The evidence also indicates a reduction of oral mucositis in adults receiving high-dose melphalan-based cancer treatment prior to haematopoietic stem cell transplantation, although there is uncertainty regarding the size of the reduction in this instance. No evidence was found for use of this preventive measure in children. Oral cryotherapy involves the placement of rounded ice chips in the mouth, which cools the oral tissues and causes  vasoconstriction . This decreases blood flow to the region and, hence, also restricts the amounts of the chemotherapy drugs delivered to the tissues. [ 5 ]


Treatment of mucositis is mainly supportive.  Oral hygiene  is the mainstay of treatment; patients are encouraged to clean their mouth every four hours and at bedtime, more often if the mucositis becomes worse. [ citation needed ]


Water-soluble jellies can be used to lubricate the mouth. Salt mouthwash can soothe the pain and keep food particles clear so as to avoid infection. Patients are also encouraged to drink plenty of liquids, at least three liters a day, and avoid alcohol. Citrus fruits, alcohol, and foods that are hot are all known to aggravate mucositis lesions. Medicinal  mouthwashes  may be used such as  Chlorhexidine gluconate  and viscous  Lidocaine  for relief of pain. However, care should be taken as the high doses of viscous  lidocaine  my cause adverse effects. [ 12 ]  A study reported that  lidocaine  has a potential toxicity; when it was tested on patients with oral mucositis who underwent a  bone marrow transplant , lidocaine anesthetic  mouthwash  was found to be systemically absorbed. [ 13 ]


Palifermin  is a human KGF (keratinocyte growth factor) that has shown to enhance epithelial cell proliferation, differentiation, and migration. Experimental therapies have been reported, including the use of cytokines and other modifiers of  inflammation  (e.g., IL-1, IL-11, TGF-beta3),  amino acid  supplementation (e.g., glutamine),  vitamins , colony-stimulating factors,  cryotherapy , and laser therapy. [ citation needed ]


Symptomatic relief of the pain of oral mucositis may be provided by barrier protection agents such as concentrated oral gel products (e.g.  Gelclair ).  Caphosol  is a mouth rinse which has been shown to prevent and treat oral mucositis caused by radiation and high-dose chemotherapy.  MuGard  is a FDA-cleared mucoadhesive oral protectant, developed by  Access Pharmaceuticals, Inc. , that is designed to form a protective hydrogel coating over the oral mucosa while a patient is undergoing chemotherapy and/or radiotherapy cancer treatments to the head and neck. [ 14 ]  Additionally, the efficacy of MuGard for the prevention or treatment of mucositis has been tested by a prospective, randomized clinical trial in which 43% of head and neck cancer patients using MuGard prophylactically never got oral mucositis.
 NeutraSal  is an FDA-cleared calcium phosphate mouth rinse that has been shown in an open-label, observational registry trial to prevent and reduce the severity of oral mucositis caused by radiation and high-dose chemotherapy.  In the trial, 56% of the radiotherapy patients reported 0 (WHO score) or no mucositis, which is significantly lower than historical rates.  Another super saturated calcium phosphate rinse on the market and cleared by the FDA is the US based  SalivaMAX.  The Mayo Clinic has been testing the antidepressant doxepin in a mouthwash to help treat symptoms. [ citation needed ]


In 2011, the FDA cleared  episil  oral liquid for the management and relief of pain of oral lesions with various etiologies, including oral mucositis/stomatitis which may be caused by chemotherapy or radiation therapy.  The transformative mechanism of action of episil creates a lipid membrane that mechanically bonds to the oral cavity mucosa to coat and soothe inflammation and ulcerations, and blanket painful lesions. [ 15 ]   In a multicenter, randomized, double-blind, single-dose study involving 38 head and neck cancer patients with oral mucositis (WHO grades 2-3) undergoing radiation therapy, episil clinically demonstrated fast-acting relief that lasted up to 8 hours. [ 16 ] [ 17 ]  Episil oral liquid is marketed in the US by  Cangene .


In a 2012 randomized controlled pilot study involving pediatric patients, topical application of honey was found to reduce recovery time compared to benzocaine gel in grade 2 and 3 chemotherapy-induced oral mucositis to a degree that was statistically significant. In grade 3 oral mucositis, honey was as effective as a mixture of honey, olive oil and propolis, while both treatments were found to reduce recovery time compared to the benzocaine control. [ 18 ]


Clinical research is ongoing in oral mucositis. A recent phase 2 exploratory trial in oral mucositis reported that dusquetide, [ 19 ] [ 20 ] [ 21 ]  a unique innate immune modulator with a mechanism that potentially addresses each of the phases of OM pathophysiology, is able to reduce the duration of severe oral mucositis, as well as reducing the incidence of infection


Natural killer cell enteropathy , also termed  NK cell enteropathy (NKCE), and a closely related disorder,  lymphomatoid gastropathy  (LG), are non-malignant diseases in which one type of  lymphocyte , the  natural killer cell  (i.e. NK cell), proliferates excessively in  the  gastrointestinal tract  (GI tract). [ 1 ]  This proliferation causes red, sore-like spots, raised lesions, erosions, and ulcers in the  mucosal  layer surrounding the GI tract lumen. Both disorders cause either no or only vague  symptoms of GI tract disturbances  such as nausea, vomiting, and  bleeding . [ 2 ]


In 2006, a persistent but apparently benign disease that involved the proliferation of NK cells at multiple sites throughout the intestines was described. This disorder appeared similar to and easily mistaken for a highly malignant disease,  extranodal NK/T-cell lymphoma, nasal type . [ 3 ]  In 2010, a similarly non-malignant disorder that involved the proliferation of NK cells in the stomach was described. The disease mimicked gastrointestinal lymphomas. [ 4 ]  Since these first descriptions, several  case series  and  case reports  have been published on these  enteropathies . [ 5 ]


The two NK cell proliferation diseases have been termed NK cell enteropathy and lymphomatoid gastropathy with NKCE being seen mostly in the United States and Korea and LG being seen mostly in Japan. [ 6 ]  Besides this geographical difference, the only other critical difference between the two diseases is that the lesions in NKCE occur in the  small intestine ,  colon , stomach, and/or  esophagus  while those of LG are limited to the stomach. [ 7 ]  Since the pathophysiological features of the two diseases are virtually identical, NKCE and LG are now commonly viewed as manifestations of the same disease. [ 2 ] [ 5 ] [ 7 ] [ 6 ] [ 8 ]


Only 36 patients with NKCE or LG have been reported as of January 2019. [ 5 ]  Nonetheless, these diseases are emerging as important clinical entities because they  1)  are newly described and likely to be diagnosed more often as they become better known and  2)  have been mistaken for, and treated as, various types of pre-malignant and malignant  lymphomas  of the GI tract. Given the radical differences in the prognoses and treatments of NKCE and LG compared to the lymphomas that they can mimic, the evaluation of many lymphocyte-proliferating disorders of the GI tract must consider and rule out the possibility that they are NKCE or LG rather than a  pre-malignant disorder  or malignant  lymphoma . [ 2 ]


Most cases of NKCE [ 9 ]  and LG [ 5 ]  have been reported in middle-aged or older individuals. Patients diagnosed with NKCE (medium age 46 years) have presented with vague abdominal pain, indigestion, vomiting, diarrhea, [ 5 ]  constipation, [ 6 ]  weight loss, anemia, and/or GI bleeding. [ 5 ]  Two patients complained of  biliary colic  (i.e. gallbladder pain) and were found to have typical lesions of NKCE in their  cystic ducts . [ 5 ]  These two cases indicate that NKCE involvement is not totally limited to the  alimentary canal . Three of 15 individuals diagnosed with NKCE disease reported no symptoms, their disease being found on  endoscopy  conducted for screening purposes. Typically, patients diagnosed with LG (medium age 58 years) have been asymptomatic at presentation with their disease being detected during GI tract examinations done for other reasons. Three of twenty patients diagnosed with LG complained of pain or discomfort in the upper abdominal region. Symptomatic individuals with either disease generally have a long history of persistent or intermittent symptoms. [ 5 ]


NK cells normally occupy the GI tract where they contribute to  innate immunity [ 7 ]  by becoming active in killing  pathogen -infected and cancerous cells. [ 10 ]  The proliferating lymphocytes in NKCE and LG express  CD56  and  CD7  proteins on their  cell surface membrane ,  CD3γ  protein in their  cytoplasm , and  granzyme B ,  perforin , and  T-cell intracellular antigen-1   cytotoxic  proteins within their  cytoplasmic granules . This pattern of protein expression identifies these cells as NK cells that, because of their expression of the cytotoxic granule-bound proteins, have been activated. [ 7 ]  However, the cause(s) for the activation of these cells as wells as for their rapid proliferation to produce NKCE [ 5 ]  and LG [ 8 ]  is unknown. To date, no evidence of NK cell  clonality  (i.e. cells developing from a single precursor) or for these cells to bear gene mutations or  chromosome abnormalities  have been reported in NKCE or LG. These findings help distinguish LB and NKCE from many lymphomas and support the conclusion that neither disease is malignant. [ 6 ]  The NK cells in LG and NKCE are not infected with the  Epstein-Barr virus  (EBV), as evidenced by their failure to express this virus's  latency proteins  and  latency ncRNAs . This finding indicates that EBV is not the cause for the NK cell activation and excessive proliferation seen in NKCE and LG and distinguishes these diseases from malignant diseases they can mimic such as extranodal NK/T-cell lymphoma, nasal type. [ 5 ]  In isolated reports, LG has occurred in individuals with  Helicobacter pylori  infection of the stomach or a history of  stomach cancer , [ 7 ]  while NKCE has been reported to occur in patients with  gluten sensitivity [ 10 ]  or circulating  anti-gliadin antibodies . Both of the latter conditions are associated with the development of GI tract lymphomas. [ 5 ]  However, the relationship of any of these findings to the  etiology  of LB and NKCE is unclear. [ 5 ]


Biopsies of NKCE tissues reveal atypical medium to large lymphocytes identified by  immunohistochemistry  to be NK cells that are multiplying at a moderately rapid rate [ 9 ]  and that lack evidence of being infected by the Epstein-Barr virus. [ 2 ]  These cells are located primarily in the  lamina propria , i.e.  loose connective tissue  lying just below the  epithelium  lining the GI tract. There is generally little invasion of these cells into the  epithelium ,  submucosa , or glands of the GI tract, and the lesions almost always show a complete absence of vascular injury due to invasion by these cells. [ 9 ]  The lesions in LG closely resemble those of NKCE. [ 5 ]


The diagnoses of NKCE and LG depends on clinical and pathological findings indicating that the two diseases:  a)  are indolent and non-malignant;  b)  usually manifested by mild, vague, or no symptoms;  c)  localize to the GI tract without involvement of the head, neck, or organs such as the liver and spleen;  d)  consist of one or more lesions localized primarily to the  lamina propria  of the esophagus, stomach, small intestine, and/or large intestine (for NKCE} or to the stomach (for LG); and  e)  involve lesions which contain medium-to large-sized, atypical, and non-clonal lymphocytes that are activated NK cells (see Pathophysiology section) which proliferate at moderately rapid rates (as gauged by, e.g. analysis of their  Ki-67 protein levels ), lack evidence of Epstein-Barr virus infection, gene mutations, or chromosome abnormalities, and show little evidence of centering around, and destroying, blood vessels. [ 9 ]


In early studies, aggressive  chemotherapy  with or without  bone marrow translanton  and  gastric resections  were used to treat NKCE and LG, respectively, based on the assumptions that these diseases were malignant. [ 5 ]  Since there was no evidence that these treatments influenced the underlying disease [ 5 ] [ 6 ]  and since NKCE and LG are essentially benign disorders, they must be distinguished from the malignant diseases which they mimic. [ 5 ]  Three malignant or potentially premalignant diseases which can closely resemble NKCE and LG along with some clinical and laboratory findings which differentiate them from NKCE and LT are:


Other diseases which NKCE and LG may superficially resemble and require consideration as being in their differential diagnoses include:  peripheral T-cell lymphoma not otherwise specified ,  T cell lymphomas  that consist of mature T cells and occur in the GI tact, [ 10 ]   MALT lymphoma  of the stomach, [ 13 ]  and other types of stomach lymphomas. [ 7 ]


Patients with NKCE or LG should be treated for symptom relief but, as currently recommended, not for the underlying NK cell proliferative disease. Regular follow-ups that include repeated endoscopic analyses of their GI tracts and tests for the spreading of the disease to other organs are recommended to insure the original diagnosis is correct. [ 2 ] [ 6 ] [ 9 ] [ 13 ]


NKCE and LG usually follow a persistent or regressing-relapsing coarse but uncommonly spontaneously relapses without a recurrence even in cases that have been mistreated with chemotherapy, bone marrow transplantation, or gastric resection. Patients with LG are less likely to have persistent or regressing-relapsing coarse. Symptoms of the disease usually remain vague and mild. [ 5 ]


Necrotizing enterocolitis  ( NEC ) is an intestinal disease that affects premature or very low birth weight infants. [ 4 ] [ 1 ]  Symptoms may include  poor feeding ,  bloating , decreased activity,  blood in the stool ,  vomiting  of  bile ,  multi-organ failure , and potentially  death . [ 1 ] [ 2 ]


The exact cause is unclear. [ 1 ]  However, several risk factors have been identified. Consistently described risk factors include  formula feeding , intestinal  dysbiosis ,  low birth weight , and  prematurity . [ 5 ]  Maternal factors such as  chorioamnionitis ,  cocaine abuse ,  intrauterine growth restriction ,  intrahepatic cholestasis during pregnancy , increased  body mass index , lack of prenatal steroids, mode of delivery,  placental abruption ,  pre-eclampsia , and  smoking  have not been consistently implicated with the development of NEC. [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]  Other risk factors potentially implicated include  congenital heart disease ,  birth asphyxia ,  exchange transfusion , and  prelabor rupture of membranes . [ 1 ]  The underlying mechanism is believed to involve a combination of  poor blood flow  and  infection  of the intestines. [ 2 ]  Diagnosis is based on symptoms and confirmed with  medical imaging . [ 1 ]


Prevention includes the use of  breast milk  and  probiotics . [ 2 ]  Treatment includes  bowel rest ,  orogastric tube ,  intravenous fluids , and intravenous  antibiotics . [ 2 ]  Surgery is required in those who have  free air in the abdomen . [ 2 ]  A number of other  supportive  measures may also be required. [ 2 ]  Complications may include  short-gut syndrome ,  intestinal strictures , or  developmental delay . [ 2 ]


About 7% of those who are born prematurely develop NEC; however the odds of an infant developing this illness is directly related to the  intensive care unit  they are placed in. [ 4 ] [ 2 ] [ 11 ] [ 12 ] [ 13 ]  Onset is typically in the first four weeks of life. [ 2 ]  Among those affected, about 25% die. [ 1 ]  The sexes are affected with equal frequency. [ 14 ]  The condition was first described between 1888 and 1891. [ 14 ]


The condition is typically seen in premature infants, and the timing of its onset is generally inversely proportional to the gestational age of the baby at birth (i.e., the earlier a baby is born, the later signs of NEC are typically seen). [ 15 ]


Initial symptoms include feeding intolerance and  failure to thrive , increased gastric residuals,  abdominal distension , and  bloody stools . Symptoms may progress rapidly to abdominal discoloration with  intestinal perforation  and  peritonitis  and systemic  hypotension  requiring  intensive medical support . [ 16 ]


The exact cause is unclear. [ 1 ]  Several risk factors have been implicated: [ 17 ]


Diagnosis is usually suspected clinically, but often requires the aid of diagnostic imaging, most commonly  radiography , which can show the intestines and may show areas with dead tissue or a bowel perforation. [ 18 ]  Specific radiographic signs of NEC are associated with specific Bell's stages of the disease: [ 19 ]


Ultrasonography  has proven to be useful, as it may detect signs and complications of NEC before they are evident on radiographs, specifically in cases that involve a paucity of bowel gas, a gasless abdomen, or a sentinel loop. [ 21 ]  Diagnosis is ultimately made in 5–10% of very-low-birth-weight infants (<1,500g). [ 22 ]


Diagnosis of NEC is more challenging in premature infants, due to inexplicit symptoms and radiographic signs. The most preterm infant is at highest risk of developing NEC. [ 23 ]


Prevention includes the use of breast milk and probiotics. [ 2 ]  A 2012 policy by the  American Academy of Pediatrics  recommended feeding preterm infants  human milk , finding "significant short- and long-term beneficial effects," including reducing the rate of NEC by a factor of one-half to three-quarters. [ 24 ]


Small amounts of oral feeds of human milk starting as soon as possible, while the infant is being primarily fed intravenously, primes the immature gut to mature and become ready to receive greater intake by mouth. [ 25 ]  Human milk from a  milk bank  or donor can be used if mother's milk is unavailable. The gut mucosal cells do not get enough nourishment from arterial blood supply to stay healthy, especially in very premature infants, where the blood supply is limited due to immature development of the capillaries, so nutrients from the lumen of the gut are needed. [ citation needed ]


Towards understanding intervention with human milk, experts have noted cow's and human milk differ in their immunoglobular and glycan compositions. [ 26 ] [ 27 ]  Due to their relative ease of production, human milk oligosaccharides (HMO) are a subject of particular interest in supplementation and intervention. [ 28 ]


A  Cochrane  review in 2020 (updated in 2023) found low- to moderate-quality evidence that supplementation of probiotics enterally "prevents severe NEC, as well as all-cause mortality in preterm infants" but cautioned that the evidence was not sufficient to inform policy and practice and that further high-quality trials are needed. [ 29 ]


Advancing  enteral feed  volumes at lower rates does not appear to reduce the risk of NEC or death in very preterm infants and seems to increase the risk of invasive infection. [ 30 ]   Not beginning feeding an infant by mouth for more than 4 days does not appear to have protective benefits. [ 31 ]


If a baby is diagnosed with NEC, treatment should begin immediately. [ 18 ]  Treatment consists primarily of supportive care, including providing bowel rest by stopping enteral feeds, gastric decompression with intermittent suction, fluid repletion to correct electrolyte abnormalities and  third-space  losses, support for blood pressure,  parenteral nutrition , [ 32 ]  and prompt antibiotic therapy.


Monitoring is clinical, although serial supine and left lateral decubitus abdominal X-rays should be performed every six hours. [ 33 ]


As an infant recovers from NEC, feeds are gradually introduced. "Trophic feeds" or low-volume feeds (<20 ml/kg/day) are usually initiated first. How and what to feed are determined by the extent of  bowel  involved, the need for surgical intervention, and the infant's clinical appearance. [ 34 ]


Where the disease is not halted through medical treatment alone, or when the  bowel perforates , immediate emergency surgery to resect the dead bowel is generally required, although abdominal drains may be placed in very unstable infants as a temporizing measure. Surgery may require a  colostomy , which may be able to be reversed at a later time. Some children may develop  short bowel syndrome  if extensive portions of the bowel must be removed. [ citation needed ]


In the case of an infant whose bowel is left in discontinuity, the surgical creation of a mucous  fistula  or connection to the distal bowel may be helpful, as this allows for refeeding of  ostomy  output to the distal bowel. This refeeding process is believed to improve bowel adaptation and aid in advancement of feeds. [ 34 ]


Typical recovery from NEC if medical, nonsurgical treatment succeeds, includes 10–14 days or more without oral intake, and then demonstrated ability to resume feedings and gain weight. Recovery from NEC alone may be compromised by co-morbid conditions that frequently accompany  prematurity . Long-term complications of medical NEC include bowel obstruction and anemia. [ citation needed ]


In the United States, NEC caused 355 deaths per 100,000 live births in 2013, down from 484 per 100,000 live births in 2009. Rates of death were almost three times higher for the black population than for the white population. [ 35 ]


When NEC is diagnosed and treated immediately, the prognosis for babies is generally very good. Most babies recover fully without any additional health problems. [ 18 ]  Overall, about 70-80% of infants who develop NEC survive. [ 36 ]   Medical management of NEC shows an increased chance of survival compared to surgical management. [ 36 ]   Despite a significant mortality risk, long-term prognosis for infants undergoing NEC surgery is improving, with survival rates of 70–80%. However, "Surgical NEC" survivors are still at risk for possible long-term complications, such as narrowing of the intestines [ 18 ]  or  Short bowel syndrome  and  neurodevelopmental disability .


The  NEC Society  is a 501(c)(3), non-profit organization dedicated to building a world without necrotizing enterocolitis (NEC) through research, advocacy, and education. The NEC Society was launched in January 2014 by Jennifer Canvasser after her son, Micah, died from complications of NEC just before his first birthday. The NEC Society is a patient-led organization that collaborates with expert clinicians and researchers to better understand, prevent, and treat this devastating neonatal intestinal disease. Today, patient-families and experts from around the world work together to improve outcomes for the most vulnerable infants at risk of NEC. Their work and numerous initiatives combine the patient-family perspective with solutions based on the best available scientific evidence.


The  NEC Society hosts an in-person, biennial Symposium where clinicians, scientists and patient-families come together to listen, learn and collaborate. It is held as an “ All-In Meeting ", where all stakeholders are fully integrated and empowered. Patient-families are central to the planning, preparation, and execution of the meeting. Each session is dedicated to a baby affected by NEC. Patient-families take part in each session as faculty and also present posters.


Neurogenic bowel dysfunction  ( NBD ) is reduced ability or inability to control  defecation  due to deterioration of or injury to the  nervous system , resulting in  fecal incontinence  or  constipation . [ 1 ]  It is common in people with  spinal cord injury  (SCI),  multiple sclerosis  (MS) or  spina bifida . [ 2 ]


The  gastrointestinal tract  (GI tract) has a complex control mechanism that relies on coordinated interaction between muscular contractions and neuronal impulses (nerve signals). [ 3 ]  Fecal incontinence or constipation occurs when there is a problem with normal bowel functioning. This could be for a variety of reasons. The normal defecation pathway involves contractions of the colon which helps mix the contents, absorb water and propel the contents along. This results in feces moving along the colon to the  rectum . [ 4 ]  The presence of stool in the rectum causes reflexive relaxation of the  internal anal sphincter  ( rectoanal inhibitory reflex ), so the contents of the rectum can move into the  anal canal . This causes the conscious feeling of the need to defecate. At a suitable time the brain can send signals causing the  external anal sphincter  and  puborectalis muscle  to relax as these are under voluntary control and this allows defecation to take place. [ 4 ] [ 5 ]


Spinal cord injury and other neurological problems mostly affect the  lower GI tract  (i.e.,  jejunum ,  ileum , and  colon ) leading to symptoms of incontinence or constipation. However, the  upper GI tract  (i.e.,  esophagus ,  stomach , and  duodenum ) may also be affected and patients with NBD often present with multiple symptoms. [ 6 ] [ 7 ]  Research shows there is a high prevalence of upper abdominal complaints, for example a study showed that approximately 22% of SCI patients reported feeling bloated, [ 6 ] [ 8 ]  and about 31% experienced abdominal distension. [ 6 ] [ 9 ]


In NBD there may be  fecal incontinence ,  constipation , or both combined. [ 10 ]  One type of constipation which may occur in people with NBD is  obstructed defecation . [ 10 ]


NBD may reduce quality of life as it often leads to difficulties with personal relationships and social life, and may also reduce self-esteem and independence. [ 5 ]  Fecal incontinence may increase the risk of  depression  and  anxiety . [ 11 ]


Different neurological disorders affect the GI tract in different ways:


Bowel dysfunction caused by a spinal cord injury will vary greatly depending on the severity and level of the spinal cord lesion. In complete spinal cord injury both sensory and motor functions are completely lost below the level of the lesion so there is a loss of voluntary control and loss of sensation of the need to defecate. [ 12 ]  An incomplete spinal cord injury is one where there may still be partial sensation or motor function below the level of the lesion. [ 12 ]


Colorectal dysfunction due to spinal cord injury can be classified in to two types: an  upper motor neuron lesion  or  lower motor neuron lesion . Problems with the upper motor neuron in a neurogenic bowel results in a hypertonic and spastic bowel because the defecation reflex centre, which causes the involuntary contraction of muscles of the rectum and anus, remains intact. [ 5 ]  However, the nerve damage results in disruption to the nerve signals and therefore there is an inability to relax the anal sphincters and defecate, often leading to constipation. [ 5 ]  An upper motor neuron lesion is one that is above the  conus medullaris  of the spinal cord and therefore above vertebral level T12. [ 13 ]  On the other hand, a lower motor neuron lesion can cause  areflexia  and a flaccid external anal sphincter so most commonly leading to incontinence. Lower motor neuron lesions are damage to nerves that are at the level of or below the conus medullaris and below vertebral level T12. However, both upper and lower motor neuron disorders can lead to constipation and/ or incontinence. [ 14 ] [ 13 ]


Spinal cord injury above the  S2 ,  S3 ,  S4  level results in preserved reflexes in the rectum and anal canal. Hence the sphincter will remain contracted. [ 12 ]  Spinal cord injury below this level results in absent reflexes. In this situation, the rectum will be flaccid and the sphincter will be relaxed. [ 12 ]


Patients with  spina bifida  have a  neural tube  that has failed to completely form. This is most commonly in the lower back area in the region of the conus medullaris or  cauda equina . Therefore, spina bifida affects the bowel similarly to a lower motor neuron spinal cord injury, resulting in a flaccid, unreactive rectal wall. The anal sphincter does not contract and close, leading to stool leakage. [ 12 ]  Most patients with spina bifida also have  hydrocephalus  which may result in intellectual deficits, thereby potentially contributing to fecal incontinence. [ 5 ]


There are a variety of symptoms associated with multiple sclerosis that are all caused by a loss of  myelin , the insulating layer surrounding the neurons (nerve cells). This means the nerve signals are interrupted and are slower. This causes muscle contractions to be irregular and fewer, resulting in an increased colon transit time. [ 12 ]  The feces stay in the colon for a longer period of time, meaning that more water is absorbed. This leads to harder stools and therefore increases the symptoms of constipation. This neurological problem can also result in reduced sensation of rectal filling and weakness of the anal sphincter because of weak muscular contraction so can cause stool leakage. [ 12 ]  In patients with multiple sclerosis, constipation and fecal incontinence often coexist, and they can be acute, chronic or intermittent due to the fluctuating pattern of MS. [ 5 ]


Damage to the defecation centre within the  medulla oblongata  of the brain can lead to bowel dysfunction. A stroke or acquired brain injury may lead to damage to this centre in the brain. Damage to the defecation centre can lead to a loss of coordination between rectal and anal contractions and also a loss of awareness of the need to defecate. [ 12 ]


This condition differs as it affects both the extrinsic and enteric nervous systems due to the decreased  dopamine  levels in both. This results in less smooth muscle contraction of the colon, increasing the colon transit time. [ 12 ]  The reduced dopamine levels also causes dystonia of the striated muscles of the pelvic floor and external anal sphincter. This explains how Parkinson's disease can lead to constipation. [ 14 ]


Twenty percent of people with  diabetes mellitus  experience fecal incontinence due to irreversible autonomic  neuropathy . This is due to the high blood glucose levels over time damaging the nerves, which can lead to impaired rectal sensation. [ 12 ]


There are different types of neurons involved in innervating the lower GI tract these include: the  enteric nervous system ; located within the wall of the gut, and the extrinsic nervous system; comprising  sympathetic  and  parasympathetic  innervation. [ 3 ]  The enteric nervous system directly controls the gut motility, whereas the extrinsic nerve pathways influence gut contractility indirectly through modifying this enteric innervation. [ 3 ]  In almost all cases of neurogenic bowel dysfunction it is the extrinsic nervous supply affected and the enteric nervous supply remains intact. The only exception is Parkinson's disease, as this can affect both the enteric and extrinsic innervation. [ 12 ]


Defecation involves conscious and subconscious processes, when the extrinsic nervous system is damaged either of these can be affected. Conscious processes are controlled by the  somatic nervous system , these are voluntary movements for example the contraction of the striated muscle of the external anal sphincter is instructed to do so by the brain, which sends signals along the nerves innervating this muscle. [ 15 ] [ 16 ]  Subconscious processes are controlled by the  autonomic nervous system ; these are involuntary movements such as contraction of the smooth muscle of the internal anal sphincter or the colon. The autonomic nervous system also provides sensory information; this could be about the level of distension within the colon or rectum. [ 15 ] [ 16 ]


In order to correctly manage neurogenic bowel dysfunction it is important to accurately diagnose it. This can be done by a variety of methods, the most commonly used would be taking a clinical history and carrying out physical examinations which may include: abdominal, neurological and rectal examinations. [ 17 ]  Patients may use the  Bristol Stool Chart  to help them describe and characterise the morphological features of their stool, this is useful as it gives an indication of the transit time. [ 18 ]  An objective method used to evaluate the motility of the colon and help with diagnosis is the colon transit time. [ 19 ]  Another helpful test to diagnose this condition may be an abdominal X-ray as this can show the distribution of feces and show any abnormalities with the colon, for example a  megacolon . [ 14 ]  Methods used for diagnosis may vary depending on if the patient is ncontinent or constipated. [ citation needed ]


Management and treatment for neurogenic bowel dysfunction depends on symptoms and biomedical diagnosis for cause of the condition. [ 14 ]  General practitioners will often refer patients to gastroenterologist to effectively manage the neurogenic bowel dysfunction. Research has been conducted on a variety of therapy and treatments for neurogenic bowel dysfunction including: diet modification, laxatives, magnetic and electrical stimulation, manual evacuation of feces and abdominal massage, enemas, and pulsed irrigation evacuation (PIE). [ 15 ] [ 20 ] [ 21 ]  Efficacy studies for pulsed irrigation evacuation with PIEMED demonstrated favorable results, removing stool of 98% of patients who used it for ineffective bowel routine, symptomatic impaction, or asymptomatic impaction. [ 20 ]  In the most severe of cases of neurogenic bowel dysfunction induced  fecal impaction , surgical interventions like colostomy are used to disrupt the dense mass of stool. [ 22 ] [ 23 ]


Non-occlusive disease  (NOD) or  Non-occlusive mesenteric ischaemia  (NOMI) is a life-threatening condition including all types of  mesenteric ischemia  without mesenteric obstruction. It mainly affects patients above 50 years of age who suffer from cardiovascular disease ( myocardial infarction ,  congestive heart failure  or  aortic regurgitation ), hepatic,  chronic kidney disease  or  diabetes mellitus . It can be triggered also by a previous  cardiac surgery  with a consequent heart shock. [ 1 ] [ 2 ]  It represents around 20% of cases of acute mesenteric ischaemia. [ 3 ]


Non-occlusive mesenteric ischemia occurs due to severe  vasoconstriction  of  mesenteric vessels  supplying the intestine.  Acute abdominal pain  is the only early acute symptom in those patients, which makes early diagnosis difficult. [ citation needed ]


CT angiography  would be helpful in differentiating occlusive from non-occlusive causes of mesenteric ischaemia. [ 4 ]


Non-occlusive disease has a poor prognosis with survival rate between 40-50%. [ 1 ] [ 3 ]


Pancolitis  or  universal colitis , in its most general sense, refers to  inflammation  of the entire  large intestine  comprising the cecum, ascending, transverse, descending, sigmoid colon and rectum. It can be caused by a variety of things such as  inflammatory bowel disease , more specifically a severe form of  ulcerative colitis . A diagnosis can be made using a number of techniques but the most accurate method is direct visualization via a  colonoscopy . [ 1 ]   Symptoms  are similar to those of ulcerative colitis but more severe and affect the entire large intestine. Patients generally exhibit symptoms including  rectal bleeding  as a result of  ulcers ,  pain in the abdominal region ,  inflammation  in varying degrees, and  diarrhea  (often  containing blood ),  fatigue ,  fever , and  night sweats . [ 2 ] [ 3 ]  Due to the loss of function in the large intestine patients may lose large amounts of weight from being unable to procure nutrients from food. [ 4 ]  In other cases the blood loss from ulcers can result in  anemia  which can be treated with  iron supplements . Additionally, due to the chronic nature of most cases of pancolitis, patients have a higher chance of developing  colorectal  cancer . [ citation needed ]


The precise causes of pancolitis are unclear, although physicians currently believe that  autoimmune diseases  and  genetic predispositions  might play a role in its progress. Genes that are known to put individuals at risk for  Crohn's disease  have been shown to also increase risk of other IBD including pancolitis. [ 5 ]  Furthermore, an individual may also develop pancolitis if ulcerative colitis of only a small portion of the colon is left untreated or worsens. [ 3 ]  Current treatment of pancolitis is focused on forcing the disease into remission, a state where the majority of the symptoms subside. Ultimately, the goal is to reach an improved quality of life, reduction in need for medicine, and minimization of the risk of cancer. [ 3 ] [ 6 ]  Medication utilized in treatment includes  anti-inflammatory agents  and  corticosteroids  to alleviate inflammation and  immunomodulators  which act to suppress the  immune system . Immunomodulators are used in severe cases of ulcerative colitis and often utilized to treat patients with pancolitis who have shown little improvement with anti-inflammatories and corticosteroids. [ 2 ] [ 3 ] [ 5 ]  However, in this case it can further expose the patient to other diseases due to the compromised immune system. A final option of treatment is available in the form of  colorectal surgery . Generally, this option is reserved for only the cases in which cancer development is highly suspected or major  internal bleeding  from ulcers occurs. In this case the entire colon and rectum  are removed  which both cures the pancolitis and prevents any chance of colon cancer. [ 7 ]


Perianal hematoma  is a  hematoma  located in, or on the border of the  anus . [ 1 ] [ 2 ]  It is sometimes inappropriately referred to as an external  hemorrhoid . [ 2 ]


The symptoms of a perianal hematoma can present over a short period of time. Pain, varying from mild to severe, [ 3 ]  will occur as the skin surrounding the rupture expands due to pressure. This pain will usually last even after the blood has clotted, and may continue for two to four days. [ citation needed ]


Perianal hematoma are caused by the rupture of a small  vein  that drains  blood  from the anus. [ 4 ]  This rupture may be the result of forceful or strained bowel movement,  anal sex  or caused by heavy lifting,  coughing  or straining. Once the rupture has formed, blood quickly pools within a few hours and, if left untreated, forms a  clot . [ citation needed ]


It is diagnosed with a visual and physical examination by a general practitioner or proctologist.


Management of thrombosed perianal hematoma has been poorly studied as of 2018. [ 5 ]  If diagnosed within the first few hours of presentation, the pooling blood may be evacuated using a  syringe . Once the blood has clotted, removal by this method is no longer possible and the clot can be removed via an incision over the lump under local anesthetic. The incision is not stitched but will heal. Care needs to be taken in regard to bleeding from the wound and possible infection with fecal bacteria. If left alone it will usually heal within a few days or weeks. [ 6 ]  The topical application of a cream containing a  heparinoid  is often advised to clear the clot. [ 7 ]


Peutz–Jeghers syndrome  (often abbreviated  PJS ) is an  autosomal dominant   genetic disorder  characterized by the development of benign  hamartomatous   polyps  in the  gastrointestinal tract  and hyperpigmented  macules  on the  lips  and  oral mucosa  ( melanosis ). [ 2 ]  This  syndrome  can be classed as one of various  hereditary  intestinal polyposis syndromes [ 3 ]  and one of various hamartomatous polyposis syndromes. [ 4 ]  It has an incidence of approximately 1 in 25,000 to 300,000 births. [ 5 ]


The risks associated with this syndrome include a substantial risk of  cancer , especially of the breast  and gastrointestinal tracts. [ 6 ] [ 7 ]  Colorectal is the most common malignancy, with a lifetime risk of 39 percent, followed by breast cancer in females with a lifetime risk of 32 to 54 percent. [ 8 ]


Patients with the syndrome also have an increased risk of developing carcinomas of the liver, lungs, breast, ovaries, uterus, testes, and other organs. Specifically, it is associated with an increased risk of  sex-cord stromal tumor with annular tubules  in the ovaries. [ 9 ]


Due to the increased risk of malignancies, direct surveillance is recommended. [ 7 ] [ 8 ]


The average age of first diagnosis is 23. The first presentation is often bowel obstruction or intussuseption from the hamartomatous gastrointestinal polyps. [ 8 ]  Dark blue, brown, and black pigmented mucocutaneous macules, are present in over 95 percent of individuals with Peutz–Jeghers syndrome. [ 8 ]  Pigmented lesions are rarely present at birth, but often appear before 5 years of age. The macules may fade during puberty. The melanocytic macules are not associated with malignant transformation. [ 8 ]


Complications associated with Peutz–Jeghers syndrome include obstruction and intussusception, which occur in up to 69 percent of patients, typically first between the ages of 6 and 18, though surveillance for them is controversial. [ 7 ] [ 8 ]  Anemia is also common due to gastrointestinal bleeding from the polyps. [ 8 ]


In 1998, a gene was found to be associated with the mutation. On  chromosome 19 , the gene known as  STK11  ( LKB1 ) [ 10 ]  is a possible  tumor suppressor gene . It is inherited in an  autosomal dominant  pattern, which means that anyone who has PJS has a 50% chance of passing the disease on to their offspring. [ citation needed ]


Peutz–Jeghers syndrome is rare and studies typically include only a small number of patients.  Even in those few studies that do contain a large number of patients, the quality of the evidence is limited due to pooling patients from many centers, selection bias (only patients with health problems coming from treatment are included), and historical bias (the patients reported are from a time before advances in the diagnosis and treatment of Peutz–Jeghers syndrome were made). Probably due to this limited evidence base, cancer risk estimates for Peutz–Jeghers syndrome vary from study to study. [ 11 ]  There is an estimated 18–21% risk of ovarian cancer, 9% risk of endometrial cancer, and 10% risk of cervical cancer, specifically  adenoma malignum . [ 9 ]


The main criteria for clinical diagnosis are: [ citation needed ]


Having two of the three listed clinical criteria indicates a positive diagnosis.  The oral findings are consistent with other conditions, such as  Addison's disease  and  McCune–Albright syndrome , and these should be included in the  differential diagnosis .  90–100% of patients with a clinical diagnosis of PJS have a mutation in the  STK11 / LKB1  gene. Molecular  genetic testing  for this mutation is available clinically. [ 12 ]


Resection of the polyps is required only if serious bleeding or intussusception occurs. Enterotomy is performed for removing large, single nodules. Short lengths of heavily involved intestinal segments can be resected. Colonoscopy can be used to snare the polyps if they are within reach. [ citation needed ]


Most patients will develop flat, brownish spots ( melanotic macules ) on the skin, especially on the lips and oral mucosa, during the first year of life, and a patient's first  bowel  obstruction due to  intussusception  usually occurs between the ages of six and 18 years. The cumulative lifetime cancer risk begins to rise in middle age. Cumulative risks by age 70 for all cancers, gastrointestinal (GI) cancers, and pancreatic cancer are 85%, 57%, and 11%, respectively. [ 13 ]


A 2011 Dutch study followed 133 patients for 14 years. The cumulative risk for cancer was 40% and 76% at ages 40 and 70, respectively. 42 (32%) of the patients died during the study, of which 28 (67%) were cancer related. They died at a median age of 45. Mortality was increased compared with the general population. [ 14 ]


A family with sinonasal polyposis were followed up for 28 years. Two cases of sinonasal type adenocarcinoma developed. This is a rare cancer. This report suggested that follow up of sinus polyps in this syndrome may be indicated. [ 15 ]


Some suggestions for surveillance for cancer include the following: [ citation needed ]


Follow-up care should be supervised by a physician familiar with Peutz–Jeghers syndrome. Genetic consultation and counseling as well as urological and gynecological consultations are often needed. [ citation needed ]


First described in a published case report in 1921 by  Jan Peutz  (1886–1957), a Dutch Internist, it was later formalized into the syndrome by American physicians at Boston City Hospital,  Harold Joseph Jeghers  (1904–1990) and Kermit Harry Katz (1914–2003), and Victor Almon McKusick (1921–2008) in 1949 and published in the  New England Journal of Medicine . [ 16 ]


Pharyngitis  is  inflammation  of the back of the  throat , known as the  pharynx . [ 2 ]  It typically results in a  sore throat  and  fever . [ 2 ]  Other symptoms may include a  runny nose ,  cough ,  headache , difficulty swallowing, swollen  lymph nodes , and a  hoarse voice . [ 1 ] [ 6 ]  Symptoms usually last 3–5 days, but can be longer depending on cause. [ 2 ] [ 3 ]  Complications can include  sinusitis  and  acute otitis media . [ 2 ]  Pharyngitis is a type of  upper respiratory tract infection . [ 7 ]


Most cases are caused by a  viral infection . [ 2 ]   Strep throat , a  bacterial infection , is the cause in about 25% of children and 10% of adults. [ 2 ]  Uncommon causes include other bacteria such as  gonococcus ,  fungi , irritants such as  smoke ,  allergies , and  gastroesophageal reflux disease . [ 2 ] [ 4 ]  Specific testing is not recommended in people who have clear symptoms of a viral infection, such as a  cold . [ 2 ]  Otherwise, a  rapid antigen detection test  or  throat swab  is recommended. [ 2 ]   PCR  testing has become common as it is as good as taking a throat swab but gives a faster result. [ 8 ]  Other conditions that can produce similar symptoms include  epiglottitis ,  thyroiditis ,  retropharyngeal abscess , and occasionally  heart disease . [ 2 ]


NSAIDs , such as  ibuprofen , can be used to help with the pain. [ 2 ]  Numbing medication, such as topical  lidocaine , may also help. [ 4 ]  Strep throat is typically treated with  antibiotics , such as either  penicillin  or  amoxicillin . [ 2 ]  It is unclear whether  steroids  are useful in acute pharyngitis, other than possibly in severe cases, but a recent (2020) review found that when used in combination with antibiotics they moderately reduced pain and the likelihood of resolution. [ 9 ] [ 10 ]


About 7.5% of people have a sore throat in any 3-month period. [ 5 ]  Two or three episodes in a year are not uncommon. [ 1 ]  This resulted in 15 million physician visits in the United States in 2007. [ 4 ]  Pharyngitis is the most common cause of a sore throat. [ 11 ]  The word comes from the  Greek word   pharynx  meaning "throat" and the suffix  -itis  meaning "inflammation". [ 12 ] [ 13 ]


Pharyngitis is a type of inflammation caused by an  upper respiratory tract infection . It may be classified as acute or chronic. Acute pharyngitis may be  catarrhal ,  purulent , or  ulcerative , depending on the  causative agent  and the  immune capacity  of the affected individual. Chronic pharyngitis may be catarrhal,  hypertrophic , or  atrophic . [ citation needed ]


Tonsillitis  is a subtype of pharyngitis. [ 14 ]  If the inflammation includes both the  tonsils  and other parts of the throat, it may be called  pharyngotonsillitis  or  tonsillopharyngitis . [ 15 ]  Another subclassification is  nasopharyngitis  (the common cold). [ 16 ]


Clergyman's sore throat  or  clergyman's throat  is an archaic term formerly used for chronic pharyngitis associated with overuse of the voice as in public speaking. It was sometimes called  dysphonia clericorum  or chronic  folliculitis  sore throat. [ 17 ]


Most cases are due to an  infectious organism  acquired from close contact with an infected individual. [ citation needed ]


These comprise about 40–80% of all infectious cases and can be a feature of many different types of viral infections. [ 11 ] [ 18 ]


A number of different bacteria can infect the human throat. The most common is  group A streptococcus  ( Streptococcus pyogenes ), but others include  Streptococcus pneumoniae ,  Haemophilus influenzae ,  Bordetella pertussis ,  Bacillus anthracis ,  Corynebacterium diphtheriae ,  Neisseria gonorrhoeae ,  Chlamydophila pneumoniae ,  Mycoplasma pneumoniae ,  and  Fusobacterium necrophorum . [ 19 ]


Streptococcal pharyngitis or strep throat is caused by a  group A beta-hemolytic streptococcus  (GAS). [ 20 ]  It is the most common bacterial cause of cases of pharyngitis (15–30%). [ 19 ]  Common symptoms include  fever ,  sore throat , and large lymph nodes. It is a contagious infection, spread by close contact with an infected individual. A definitive diagnosis is made based on the results of a  throat culture .  Antibiotics  are useful to both prevent complications (such as  rheumatic fever ) and speed recovery. [ 21 ]


Fusobacterium necrophorum  is a normal inhabitant of the oropharyngeal  flora  and can occasionally create a  peritonsillar abscess . In one out of 400 untreated cases,  Lemierre's syndrome  occurs. [ 22 ]


Diphtheria  is a potentially life-threatening upper respiratory infection caused by  Corynebacterium diphtheriae , which has been largely eradicated in developed nations since the introduction of childhood  vaccination  programs, but is still reported in the  Third World  and increasingly in some areas in  Eastern Europe . Antibiotics are effective in the early stages, but recovery is generally slow. [ citation needed ]


A few other causes are rare, but possibly fatal, and include  parapharyngeal space  infections:  peritonsillar abscess  ("quinsy abscess"),  submandibular space infection  (Ludwig's angina), and  epiglottitis . [ 23 ] [ 24 ] [ 25 ]


Some cases of pharyngitis are caused by  fungal infection , such as  Candida albicans , causing  oral thrush . [ 26 ]


Pharyngitis may also be caused by mechanical, chemical, or thermal irritation, for example cold air or  acid reflux . Some medications may produce pharyngitis, such as  pramipexole  and  antipsychotics . [ 27 ] [ 28 ]


Differentiating a viral and a bacterial cause of a sore throat based on symptoms alone is difficult. [ 29 ]  Thus, a throat swab often is done to rule out a bacterial cause. [ 30 ]


The modified  Centor criteria  may be used to determine the management of people with pharyngitis. Based on five clinical criteria, it indicates the probability of a streptococcal infection. [ 21 ]


One point is given for each of the criteria: [ 21 ]


The  Infectious Disease Society of America  recommends against  empirical treatment  and considers antibiotics only appropriate following positive testing. [ 29 ]  Testing is not needed in children under three, as both group A strep and  rheumatic fever  are rare, except if they have a sibling with the disease. [ 29 ]


The majority of the time, treatment is symptomatic. Specific treatments are effective for bacterial, fungal, and  herpes simplex  infections.


Gargling  salt water  is often suggested, but there is no evidence to support or discourage this practice. [ 4 ]   Alternative medicines  are promoted and used for the treatment of sore throats. [ 37 ]  However, they are poorly supported by evidence. [ 37 ]


Acute pharyngitis is the most common cause of a  sore throat  and, together with cough, it is diagnosed in more than 1.9 million people a year in the United States. [ 11 ]


Pneumatosis intestinalis  (also called  intestinal pneumatosis ,  pneumatosis cystoides intestinalis ,  pneumatosis coli , or  intramural bowel gas ) is  pneumatosis  of an  intestine , that is, gas  cysts  in the bowel wall. [ 1 ] [ 2 ]  As a  radiological sign  it is highly suggestive for  necrotizing enterocolitis . This is in contrast to gas in the  intestinal lumen  (which is relieved by  flatulence ). In  newborns , pneumatosis intestinalis is considered  diagnostic  for necrotizing enterocolitis, and the gas is produced by bacteria in the bowel wall. [ 3 ]  The pathogenesis of pneumatosis intestinalis is poorly understood and is likely multifactorial.  PI itself is not a disease, but rather a clinical sign.  In some cases, PI is an incidental finding, whereas in others, it portends a life-threatening intra-abdominal condition. [ citation needed ]


This  medical sign  article is a  stub . You can help Wikipedia by  expanding it .


Pouchitis  is an umbrella term for inflammation of the  ileal pouch , an artificial rectum surgically created out of ileum (the last section of the small intestine) in patients who have undergone a  proctocolectomy  or total colectomy (removal of the colon and rectum). [ 1 ]  The ileal pouch-anal anastomosis is created in the management of patients with  ulcerative colitis ,  indeterminate colitis ,  familial adenomatous polyposis ,  cancer , or rarely, other  colitides . [ 2 ] [ 3 ]


A variety of mechanisms can be the cause of pouchitis including inflammatory factors such as a dysbiosis sparked inflammation or Crohn's disease of the pouch, surgical causes including surgical join leaks and pelvic sepsis, or infectious from  Clostridioides difficile  (C Diff) or  Cytomegalovirus  (CMV).  It is possible to have more than one factor causing pouch inflammation at the same time. [ 4 ]


The incidence of a first episode of pouchitis at 1, 5 and 10 years post-operatively is 15%, 33%, and 45% respectively. [ 3 ] [ 5 ]


Patients with pouchitis typically present with bloody  diarrhea , urgency in passing stools, or discomfort while passing stools.  The loss of blood and/or dehydration resulting from the frequent stools will frequently result in nausea.  Extreme cramping and pain can occur with pouchitis.


Endoscopic  evaluation of the pouch ( pouchoscopy ) in patients with pouchitis usually reveals erythematous pouch  mucosa , loss of pseudocolonic vasculature or other architecture, and friability of the mucosa.  Biopsies show evidence of inflammatory cells or  red blood cells  in the  lamina propria .


Symptoms of pouchitis include increased stool frequency, urgency, incontinence, nocturnal seepage, abdominal cramping, pelvic discomfort, and  arthralgia . [ 6 ]


Symptom severity does not always correlate with severity of endoscopically or histologically evaluated pouch inflammation. [ 6 ]  Additionally, these symptoms are not necessarily specific for pouchitis, as they may arise from other inflammatory or functional pouch disorders such as  Crohn's disease  of the pouch,  cuffitis , pouch sinus, or irritable pouch syndrome. [ 6 ]  The most reliable tool for diagnosis is endoscopy combined with histologic features (derived from tissue  biopsies  obtained during endoscopy). [ 6 ]


Once a diagnosis of pouchitis is made, the condition is further classified. The activity of pouchitis is stratified as: [ citation needed ]


The duration of pouchitis is defined as acute (less than or equal to four weeks) or chronic (four weeks or more) and the pattern classified as infrequent (1–2 acute episodes), relapsing (three or fewer episodes) or continuous. Finally, the response to medical treatment as labelled as treatment responsive or treatment refractory, with the medication for either case being specified. [ citation needed ]


First line treatment is usually with  antibiotics , specifically with  ciprofloxacin  and  metronidazole . [ 7 ]   Ampicillin  or  piperacillin  can also be considered as alternatives to empiric ciprofloxacin and metronidazole.  Administration of metronidazole at a high daily dose of 20 mg/kg can cause symptomatic peripheral  neuropathology  in up to 85% of patients. This can be a limiting factor in the use of maintenance metronidazole to suppress chronic pouchitis. [ 8 ] [ 9 ]


Other therapies which have been shown to be effective include  probiotics  for pouchitis, [ 10 ]  the application of which usually begins as soon as any antibiotic course is completed so as to re-populate the pouch with beneficial bacteria.


Biologics , such as anti-tumor necrosis factor antibodies, may also be useful but the evidence for their use is largely anecdotal.


A pilot study on the effect of reducing dietary  FODMAP  intake on bowel function in people without a colon indicates there might be a relation between pouchitis and FODMAP diets. [ 11 ]


Alicaforsen  (an  antisense  inhibitor which targets the  messenger RNA  for the production of human  ICAM-1  protein) was evaluated in a Phase 3 clinical trial, which did not meet the co-primary endpoints in the primary analysis (an adaptation of the Mayo Score of improvement in endoscopic remission and bowel frequency). [ 12 ]


Proctocolitis  is a general term for  inflammation  of the  rectum  and  colon . [ 1 ]


Proctocolitis has many possible causes. Common infectious causes of proctocolitis include  Chlamydia trachomatis , LGV ( Lymphogranuloma venereum ),  Neisseria gonorrhoeae ,  HSV , and  Helicobacter  species. It can also be idiopathic (see  colitis ), vascular (as in  ischemic colitis ), or autoimmune (as in  inflammatory bowel disease ). [ citation needed ]


Anoscopy  can be used to diagnose the majority of cases of proctocolitis. [ 2 ]


Antibiotics, such as  ceftriaxone  and  doxycycline , if there is  infection [ citation needed ]


Protein losing enteropathy  ( PLE ) is a syndrome in which  blood proteins  are lost excessively via the  gastrointestinal (GI) tract . It may be caused by many different underlying diseases that damage the lining of the GI tract ( mucosa ) or cause blockage of its  lymphatic drainage . [ 3 ]


The signs and symptoms of protein losing  enteropathy  include diarrhea, fever, and general abdominal discomfort. [ 4 ]  Swelling of the legs due to  peripheral edema  can also occur; however, if the PLE is related to a systemic disease such as  congestive heart failure  or  constrictive pericarditis , then these symptoms could be due directly to the underlying illness. [ 2 ]   In severe cases,  anasarca , a generalized form of edema, may develop. [ 5 ]


The causes of protein-losing enteropathy can include GI conditions (among other causes), like the following: [ 1 ]


The pathophysiology of protein losing enteropathy is a result of plasma protein loss to the GI tract  lumen . [ 2 ]  PLE is a complication of a disorder, be it lymphatic obstruction or mucosal injury. [ 7 ]


Protein losing enteropathy is a syndrome, characterized by a collection of signs and symptoms that are due to an underlying primary medical condition. Thus, there are many different pathophysiologic mechanisms of intestinal protein loss. Erosive disease, is characterized by mucosal damage or erosions of the colon  intestinal epithelium  and  capillary  bed underlying the epithelium, leading to a leakage of proteins from the capillaries into the  interstitial  space and then into the intestinal lumen where they are lost from the body. [ 8 ]  This type of inflammation may be seen in  inflammatory bowel diseases ,  peptic ulcers  and infections. [ 8 ]  A second pathological mechanism, the non-erosive type, is characterized by increased intestinal permeability causing protein to be lost from the interstitium into the intestinal lumen. [ 8 ]  This increased intestinal permeability may be seen in  eosinophilic gastroenteritis  and other conditions causing increased inflammation in the gut, or certain genetic disorders affecting the cell adhesions between gut  enterocytes . [ 8 ]  And a third type is due to intestinal  lymphangiectasia  in which the lymphatic vessels that drain interstitial fluid from the gut are damaged, leading to a blockage of lymphatic drainage and a buildup of interstitial fluid near the gut, thus causing leakage of proteins into the gut. [ 8 ]  This may be due to primary or congenital disease states of the lymphatic system or secondary (acquired) damage to the lymphatic system. [ 8 ]  Possible secondary causes of lymphangiectasis include  congestive heart failure  or  constrictive pericarditis . These conditions cause an increase in the  central venous pressure . The lymphatic system drains into the central venous system following a negative pressure gradient to the  subclavian vein  via the  thoracic duct  or  right lymphatic duct . However, any pathological mechanism that leads to increased central venous pressure may also cause increased lymphatic pressure, thus impairing lymphatic drainage at the gut and lead to protein losing enteropathy. [ 8 ]  Certain infections such as  Whipple disease  can also lead to impaired lymphatic drainage by destroying the lymphatic  lacteals , which are lymphatic capillaries underlying  intestinal villi  and facilitating the drainage of lymph from the gut. [ 8 ]  Congenital disorders of the lymphatic system such as  Primary Intestinal Lymphangiectasia  are due to congenitally dilated or malformed lacteals that lead to lymph leakage into the small bowel, causing protein loss and protein losing enteropathy. [ 9 ]


The widespread hypoproteinemia seen in protein losing enteropathy may present with complications related to the specific proteins lost, especially in severe disease. A decrease in  antibodies  (also known as immune globulins) may lead to an increased susceptibility to infections. [ 8 ]  And the loss of inhibitory coagulation factors may lead to a  hypercoagulable state . [ 8 ]


In  pediatric protein losing enteropathy , changes in  epithelial  cells contribute to the pathogenesis of PLE by augmenting the rate of efflux of serum proteins. Congenital molecular mutations, poor lymphatic drainage and/or inflammation may cause epithelial  matrix  changes. [ 10 ]  The absence of  proteoglycans , which are  glycosaminoglycan  chains attached to protein, may contribute to PLE and augment inflammatory  cytokines . Children who have certain  congenital glycosylation defects  may have protein losing enteropathy. [ 10 ] [ 11 ]


The diagnosis of protein losing enteropathy is made by excluding other causes of protein loss.  Endoscopy  can be used to localize the cause of the protein loss in the bowel. Different methods of quantifying protein loss in the bowel include faecal excretion of  alpha 1-antitrypsin , a marker of protein losing enteropathy, as well as viral serologies, which may be useful to determine the cause of the PLE. [ 1 ]  Alpha 1-antitrypsin is a blood protein that is lost in the gut, however, it is not actively secreted or absorbed by the gut, and it resists proteolysis in the gut lumen, thus making it a preferred protein for quantification of gut protein loss in protein losing enteropathy. [ 8 ]  Fecal alpha 1-antitrypsin may be quantified in a random stool sample, or more accurately, in a 24-hour stool sampling to quantify the amount of protein loss in PLE. [ 8 ]  In suspected cases of local disease, or when PLE is suspected to be due to lymph drainage abnormalities,  lymphangiography  may be used to localize the areas of lymphatic leakage. [ 8 ]  Imaging of the  thoracic  or  abdominopelvic  cavities may also aid in the diagnosis, possibly by identifying masses impairing lymphatic and venous drainage from the intestines and thus contributing to PLE. [ 8 ]


Treatment for protein losing enteropathy depends upon the underlying condition; according to Rychik and Spray (2002) this could mean treatment of  hypoproteinemia  or of the  intestinal mucosa . [ 12 ]


For causes related to the heart, treatment for PLE after the  Fontan operation  treatment must be equal to the level of hypoproteinemia present. Therefore, it is useful to categorize patients based on their serum  albumin  levels, if less than normal (typically less than 3.5 g/dL) but greater than 2.5 g/dL, this can be seen as a mild form of protein losing enteropathy. Symptomatic management of edema with  furosemide  (and aldactone) can provide relief for the individual with mild hypoproteinemia. [ 13 ] [ 14 ]


Dogs can also suffer from PLE. Because the proteins are lost from the intestine, these dogs have low levels of albumin in the blood. Chronic enteropathy is one of the possible reasons for PLE and it has been shown in a study that hypoalbuminaemia is a risk factor for negative outcome and the prognosis is guarded for these dogs. [ 15 ]  Gastrointestinal lymphoma and intestinal lymphangiectasia are other diseases that can cause protein losing enteropathy in dogs. [ 16 ]  The Breed Lundehunds seem to be predisposed for PLE. [ 17 ]


Pseudodiarrhea , also known as  hyperdefecation  or excess stool, is defined as increased stool frequency (more than three times daily) with a normal daily stool weight of less than 300 g. [ 1 ]


Pseudodiarrhea is often associated with rectal urgency and accompanies  irritable bowel syndrome ,  hyperthyroidism , and anorectal disorders such as  proctitis .  Patients with rectal obstruction (e.g., from fecal impaction, obstruction due to a vaginal  pessary ) may also present with pseudodiarrhea, since only liquid stool can make it through. [ 2 ] [ 3 ]


Pseudodiarrhea may be more common than chronic diarrhea and should always be considered in patients complaining of chronic diarrhea. [ citation needed ]


Radiation enteropathy  is a  syndrome  that may develop following abdominal or pelvic  radiation therapy  for  cancer . [ 1 ] [ 2 ]  Many affected people are  cancer survivors  who had treatment for  cervical cancer  or  prostate cancer .  It has also been termed  pelvic radiation disease  with  radiation proctitis  being one of its principal features [ 3 ]  and  radiation-induced lumbar plexopathy (RILP)  being a rare consequence. [ 4 ]


People who have been treated with  radiotherapy  for pelvic and other abdominal cancers frequently develop gastrointestinal symptoms. [ 3 ] [ 1 ] [ 2 ]


These include:


Gastrointestinal symptoms are often found together with those in other systems including  genitourinary disorders  and  sexual dysfunction . The burden of symptoms substantially impairs the patients'  quality of life . [ citation needed ]


Nausea, vomiting, fatigue, and diarrhea may happen early during the course of radiotherapy.  Radiation enteropathy represents the longer-term, chronic effects that may be found after a latent period most commonly of 6 months to 3 years after the end of treatment.  In some cases, it does not become a problem for 20–30 years after successful curative therapy. [ 1 ]


A large number of people receive abdominal and or pelvic  radiotherapy  as part of their cancer treatment with 60–80% experiencing gastrointestinal symptoms. [ 1 ]   This is used in standard therapeutic regimens for  cervical cancer ,  prostate cancer ,  rectal cancer ,  anal cancer ,  lymphoma  and other abdominal malignancies.  Symptoms can be made worse by the effects of surgery, chemotherapy or other drugs given to treat the cancer. [ 5 ]   Improved methods of radiotherapy have reduced the exposure of non-involved tissues to radiation, concentrating the effects on the cancer.  However, as the parts of the intestine such as the  ileum  and the  rectum  are immediately adjacent to the cancers, it is impossible to avoid some radiation effects. [ 1 ]   Previous intestinal surgery, obesity, diabetes, tobacco smoking and vascular disorders increase the chances of developing enteropathy. [ 1 ]


Early radiation enteropathy is very common during or immediately after the course of radiotherapy.  This involves cell death, mucosal  inflammation  and epithelial barrier dysfunction. This injury is termed  mucositis  and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain. [ 1 ] [ 6 ]   It recovers within a few weeks or months.


The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes  intestinal   epithelial  mucosal  atrophy , vascular  sclerosis , and progressive  fibrosis  of the  intestinal wall , among other changes in intestinal  neuroendocrine  and immune cells and in the  gut microbiota . [ 1 ] [ 6 ]  These changes may produce  dysmotility , strictures,  malabsorption  and bleeding.  Problems in the terminal ileum and rectum predominate. [ citation needed ]


Multiple disorders are found in patients with radiation enteropathy, so guidance including an algorithmic approach to their investigation has been developed. [ 5 ] [ 7 ]   This includes a holistic assessment with investigations including  upper endoscopy ,  colonoscopy , breath tests and other nutritional and gastrointestinal tests.  Full investigation is important as many cancer survivors of radiation therapy develop other causes for their symptoms such as  colonic polyps ,  diverticular disease  or  hemorrhoids . [ 8 ]


Prevention of radiation injury to the small bowel is a key aim of techniques such as  brachytherapy , field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy.  Medications including  ACE inhibitors ,  statins  and  probiotics  have also been studied and reviewed. [ 2 ] [ 9 ]


In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others. [ 1 ]  Medical treatments include the use of  hyperbaric oxygen  which has beneficial effects in  radiation proctitis  or anal damage. [ 10 ]  Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and  vitamin B12  or  vitamin D  supplements, together with  bile acid sequestrants  for  bile acid diarrhea  and possibly antibiotics for  small intestinal bacterial overgrowth . [ 2 ]  Probiotics have all been suggested as another therapeutic avenue. [ 11 ]


Endoscopic therapies including  argon plasma coagulation  have been used for bleeding  telangiectasia  in radiation proctitis and at other intestinal sites, although there is a rick of perforation. [ 2 ]


Surgical treatment may be needed for  intestinal obstruction ,  fistulae , or perforation, which can happen in more severe cases. [ 12 ]   These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common. [ citation needed ]
A systematic review has found there is some promising evidence for non-surgical interventions for late rectal damage, however due to low quality evidence no conclusions could be drawn. [ 13 ]  Optimal treatment usually produces significant improvements in quality of life. [ 3 ]


An increasing number of people are now surviving cancer, with improved treatments producing cure of the malignancy ( cancer survivors ).  There are now over 14 million such people in the US, and this figure is expected to increase to 18 million by 2022. [ 14 ]   More than half are survivors of abdominal or pelvic cancers, with about 300,000 people receiving abdominal and pelvic radiation each year.  It has been estimated there are 1.6 million people in the US with post-radiation intestinal dysfunction, a greater number than those with  inflammatory bowel disease  such as  Crohn's disease  or  ulcerative colitis . [ 1 ]


New agents have been identified in animal studies that may have effects on intestinal radiation injury. [ 1 ]   The research approach in humans has been reviewed. [ 15 ]


Radiation proctitis  or  radiation proctopathy  is a condition characterized by damage to the rectum after exposure to  x-rays  or other  ionizing radiation  as a part of  radiation therapy . [ 1 ]  Radiation proctopathy may occur as acute inflammation called  "acute radiation proctitis"  (and the related  radiation colitis ) or with chronic changes characterized by  radiation associated vascular ectasiae (RAVE) and chronic radiation proctopathy . [ 2 ] [ 1 ]   Radiation proctitis most commonly occurs after pelvic radiation treatment for  cancers  such as  cervical cancer ,  prostate cancer ,  bladder cancer , and  rectal cancer . RAVE and chronic radiation proctopathy involves the lower  intestine , primarily the  sigmoid colon  and the rectum, and was previously called chronic radiation proctitis,  pelvic radiation disease  and  radiation enteropathy . [ 3 ]


Acute radiation proctopathy often causes pelvic pain, diarrhea, urgency, and the urge to defecate despite having an empty colon (tenesmus). [ 4 ]  Hematochezia and fecal incontinence may occur, but are less common. [ 4 ]  Chronic radiation damage to the rectum (>3 months) may cause rectal bleeding, incontinence, or a change in bowel habits secondary. Severe cases may lead to with strictures or fistulae formation. [ 5 ] [ 4 ]  Chronic radiation proctopathy can present at a median time of 8-12 months following radiation therapy. [ 4 ]


Acute radiation proctopathy occurs due to direct damage of the lining ( epithelium ) of the colon. [ 1 ]  Rectal biopsies of acute radiation proctopathy show superficial depletion of epithelial cells and acute inflammatory cells located in the lamina propria. [ 4 ]  By contrast, rectal biopsies of RAVE and chronic radiation proctopathy demonstrates ischemic endarteritis of the submucosal arterioles, submucosal fibrosis, and neovascularization. [ 4 ]


Where chronic radiation proctopathy or RAVE is suspected, a thorough evaluation of symptoms is essential. Evaluation should include an assessment of risk factors for alternate causes of proctitis, such as  C. difficile colitis ,  NSAID use , and travel history. [ 6 ]  Symptoms such as diarrhea and painful defecation need to be systematically investigated and the underlying causes each carefully treated. [ 7 ]  Testing for parasitic infections ( amebiasis ,  giardiasis ) and sexually transmitted infections ( Neisseria gonorrhoeae  and  herpes simplex virus ) should be considered. [ 6 ]  The location of radiation treatment is important, as radiation directed at regions of the body other than the pelvis (eg brain, chest, etc) should  not  prompt consideration of radiation proctopathy. [ 6 ]


Endoscopy is the mainstay of diagnosis for radiation damage to the rectum, with either  colonoscopy  or  flexible sigmoidoscopy . RAVE is usually recognized by the macroscopic appearances on endoscopy characterized by vascular ectasias. [ 8 ]  Mucosal biopsy may aid in ruling out alternate causes of proctitis, but is not routinely necessary and may increase the risk of fistulae development. [ 6 ]   Telangiectasias  are characteristic and prone to bleeding. [ 3 ]  Additional endoscopic findings may include pallor (pale appearance), edema, and friability of the mucosa.


Radiation proctitis can occur a few weeks after treatment, or after several months or years:


Several methods have been studied in attempts to lessen the effects of radiation proctitis. Acute radiation proctitis usually resolves without treatment after several months. When treatment is necessary, symptoms often improve with hydration, anti-diarrheal agents, and discontinuation of radiation. [ 4 ]   Butyrate   enemas  may also be effective. [ 9 ] [ 10 ]


In contrast, RAVE and chronic radiation proctopathy usually is not self-limited and often requires additional therapies. [ 4 ]  These include  sucralfate ,  hyperbaric oxygen therapy ,  corticosteroids ,  metronidazole ,  argon plasma coagulation ,  radiofrequency ablation  and  formalin  irrigation. [ 1 ] [ 3 ] [ 11 ]  The average number of treatment sessions with argon plasma coagulation to achieve control of bleeding ranges from 1 to 2.7 sessions. [ 4 ]


In rare cases that do not respond to medical therapy and endoscopic treatment, surgery may be required.  Overall, less than 10 percent of individuals with radiation proctopathy require surgery. [ 4 ]  In addition, complications such as obstruction and fistulae may require  surgery .


Up to 30 percent of individuals who receive pelvic radiation therapy for cancer may develop radiation proctopathy. [ 4 ]


Rectal bleeding  refers to  bleeding  in the  rectum , thus a form of  lower gastrointestinal bleeding . There are many causes of rectal hemorrhage, including inflamed  hemorrhoids  (which are dilated vessels in the perianal fat pads), rectal  varices ,  proctitis  (of various causes),  stercoral ulcers , and  infections .  Diagnosis is usually made by  proctoscopy , which is an  endoscopic  test. [ 1 ]


Those with rectal bleeding may notice bright red blood in their stool. Symptoms associated with rectal bleeding include having several bowel movements in a day, feelings of incomplete rectal evacuation, straining, hard or lumpy stools, feelings of urgency, loose or watery stools, and leakage of bowel movement. [ 2 ]


Bleeding from the rectal area could indicate premalignant  polyps  or  colorectal cancer . [ 3 ]  Compared to  colorectal cancer ,  anal lesions  or benign colorectal conditions are far more common causes of rectal bleeding. [ 4 ]  Other causes of rectal bleeding include  hemorrhoids , full-thickness  rectal prolapse ,  fissures , sentinel tags,  ulcers ,  rhagades , external  thromboses  with extravasation of blood clot, prolapsed  polyps  or tags, anal trauma or anal-receptive intercourse,  abscess ,  fistula  opening, dermatologic conditions of the perianal region, hypertrophied papilla, and distal  proctitis . An ulcer could be caused by  Crohn's disease ,  anal cancer ,  HIV , or another  STD .  Inflammatory bowel diseases  may also cause rectal bleeding. [ 5 ]


Certain medications, such as  calcium channel blockers  or  proton pump inhibitors , can exacerbate anorectal symptoms by causing  diarrhea  or  constipation , or they can exacerbate bleeding (e.g.,  Coumadin ,  nonsteroidal anti-inflammatory drugs ). A history of  hemorrhoidectomy , fissure surgery, fistula surgery,  polypectomy , or  colectomy  may be relevant. Gastrointestinal symptoms can also result from other procedures like  gastric bypass  or  cholecystectomy . Any prior assessment, such as a  colonoscopy  or flexible  sigmoidoscopy , may also be important, as well as any history of  polypectomy  carried out in connection with one of these operations. [ 5 ]


Any complaint of bleeding should be followed up with a  complete blood count  (CBC) in order to determine the extent of the bleeding and guide treatment. The  partial thromboplastin time  (PTT) and the  international normalized ratio  (INR), which can be used to detect bleeding tendencies, are additional crucial lab tests to obtain. [ 6 ]


Testing for  STIs , such as  gonorrhea  and  chlamydia , should be conducted on patients who engage in anal receptive sex. [ 6 ]  No matter if there are other clinical symptoms present or not,  endoscopies  are the gold standard for examining rectal bleeding and should be completed on patients over 40. To check for a distal source of bleeding, such as internal  hemorrhoids ,  proctitis ,  rectal ulcers ,  malignancies , or  varices , one can use an  anoscope  or rigid procto- sigmoidoscope . When proximal lower GI pathology is suspected, a colonoscopy needs to be performed. [ 7 ]


If there is a significant amount of bleeding or the patient is too unstable to be put under anesthesia for an endoscopic procedure,  CT angiography  may be pursued. It could be challenging to pinpoint the precise location of the blood if there is a lot of blood in the stomach. [ 6 ]


Tagged red blood cell  scintigraphies  are a precise way to locate the bleeding vessels and pinpoint the area where they are bleeding. It can be applied to chronic and recurrent rectal bleeding with no apparent cause. [ 6 ]


Rectitis  is an inflammation of the inner  rectum . It mainly affects the rectal  mucous membrane . [ 1 ]   The condition can be acute or it may be a chronic condition. Rectitis may be caused due to conditions such as  ulcerative colitis  or  Chron's disease . [ 1 ]


The Restroom Access Act , also known as  Ally's Law , is legislation passed by several U.S. states that requires retail establishments that have toilet facilities for their employees to also allow customers to use the facilities if the customer has a medical condition requiring immediate access to a toilet, such as  inflammatory bowel disease  or  Crohn’s disease .


The law is named for Ally Bain, a 14-year-old girl from Illinois who had a flare-up of her  Crohn's disease  while shopping at a large retail store and was subsequently denied use of the employee-only restroom, causing her to soil herself. Bain's mother vowed it would never happen to anyone else. The two met with Illinois State Representative  Kathy Ryg , helped her draft a bill, and testified before a committee at the state capital. The bill was signed into law in August 2005, making Illinois the first U.S. state to do so.


As of January 2024, at least 20 U.S. states had passed versions of the law. They include Arkansas, California, [ 1 ]  Colorado, Connecticut, Delaware, [ 2 ]
Illinois, Kentucky, Louisiana, [ 3 ]  Maryland, Massachusetts, Michigan, Minnesota, New Hampshire, [ 4 ]  New York, Ohio, Oregon, Tennessee, Texas, Wisconsin, and Washington. [ 5 ] [ 6 ]  A Virginia bill, which levies fines of $100 for non-compliance, was adopted in the 2024 General Assembly session and went in to effect on July 1, 2024. [ 7 ]


There is support for a federal version of the act, but some small-business people object to the public using their employee bathrooms. [ 8 ] [ 5 ]


In general, each state requires that the customer present a document signed by a medical professional attesting that the customer uses an  ostomy  device or has  Crohn's disease ,  ulcerative colitis , or other  inflammatory bowel disease  or medical condition requiring access to a toilet facility without delay. In at least two states, Oregon and Tennessee, the customer can present an identification card issued by a national organization advocating for the eligible medical condition. [ 9 ] [ 6 ]


Some states also include pregnancy as a covered medical condition. [ 5 ]


The Restroom Access Act of  Illinois  states:


In Australia, the association Crohn's & Colitis Australia (CCA) encourages businesses to support people with such medical conditions by recognizing the Can't Wait Card issued by the CCA. [ 11 ]  The CCA states:


Other countries including the UK have similar programs of voluntary participation by businesses, one such program in the UK is the Bladder & Bowel Community's Just Can't Wait Card. [ 14 ]


A card with no country specific indications is available explaining the possibility of legislation and the gravity of the card holders disability and need for restroom access. [ citation needed ]


Retained antrum syndrome  or retained gastric antrum syndrome is one of the rare  postgastrectomy syndromes . It happens after  Billroth II  surgery and the mechanism involved is the inadequate removal of the distal  antrum  and  pylorus  during resection of the antrum and  gastrojejunostomy . [ 1 ] [ 2 ]


Lack of the usual acid-secreting  gastric glands  makes the  antral segment  continually exposed to the alkaline environment of the duodenum, which causes it to secrete excessive acid and be prone to form  ulcers . [ 2 ]


Sandifer syndrome  (or  Sandifer's syndrome ) is an  eponymous   paediatric  medical disorder, characterised by  gastrointestinal  symptoms and associated  neurological  features. [ 1 ] [ 2 ] [ 3 ]  There is a significant correlation between the  syndrome  and  gastro-oesophageal reflux disease  (GORD); however, it is estimated to occur in less than 1% of children with reflux. [ 4 ]


Onset is usually confined to infancy and early childhood, [ 2 ]  with peak prevalence at 18–36 months. [ 4 ]   In rare cases, particularly where the child is severely mentally impaired, onset may extend to adolescence. [ 4 ]


The classical symptoms of the syndrome are  spasmodic torticollis  and  dystonia . [ 3 ] [ 4 ] [ 5 ]   Nodding and rotation of the head, neck extension, gurgling, writhing movements of the limbs, and severe  hypotonia  have also been noted. [ 3 ]


Spasms may last for 1–3 minutes and may occur up to 10 times a day.  Ingestion of food is often associated with occurrence of symptoms; this may result in reluctance to feed.  Associated symptoms, such as  epigastric  discomfort, vomiting (which may involve  blood ) and abnormal eye movements have been reported.  Clinical signs may also include anaemia. [ 2 ]


Diagnosis is made on the basis of the association of gastro-oesophageal reflux with the characteristic movement disorder. Neurological examination is usually normal. Misdiagnosis as benign infantile spasms or epileptic seizures is common, particularly where clear signs or symptoms of gastro-oesophageal reflux are not apparent. Early diagnosis is critical, as treatment is simple and leads to prompt resolution of the movement disorder. [ 2 ]


Successful treatment of the associated underlying disorder, such as GORD or hiatus hernia, may provide relief. [ 4 ]


Sandifer syndrome is not typically life-threatening [ 4 ]  and the prognosis is typically good. [ 2 ]


Sandifer syndrome was first described in 1964 by Austrian neurologist  Marcel Kinsbourne  in  The Lancet . [ 6 ] [ 7 ]  Kinsbourne named the syndrome after his mentor, British neurologist  Paul Sandifer , who had initially cared for the patients described in Kinsbourne's case reports. [ 8 ] [ 9 ] [ 10 ]


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Small intestinal bacterial overgrowth  ( SIBO ), also termed  bacterial overgrowth , or  small bowel bacterial overgrowth syndrome  ( SBBOS ), is a disorder of excessive  bacterial  growth in the  small intestine . Unlike the  colon  (or large bowel), which is rich with bacteria, the small bowel usually has fewer than 100,000 organisms per millilitre. [ 1 ]  Patients with bacterial overgrowth typically develop symptoms which may include  nausea ,  bloating ,  vomiting ,  diarrhea ,  malnutrition ,  weight loss , and  malabsorption [ 2 ]  by various mechanisms.


The  diagnosis  of bacterial overgrowth is made by a number of techniques, with the  gold standard [ 3 ]  being an  aspirate  from the  jejunum  that grows in excess of 10 5   bacteria  per millilitre.  Risk factors  for the development of bacterial overgrowth include dys motility ;  anatomical  disturbances in the bowel, including  fistulae ,  diverticula  and  blind loops  created after surgery, and resection of the  ileo-cecal valve ;  gastroenteritis -induced alterations to the small intestine; and the use of certain medications, including  proton pump inhibitors .


Small bowel bacterial overgrowth syndrome is treated with an  elemental diet  or  antibiotics , which may be given in a cyclic fashion to prevent tolerance to the antibiotics, sometimes followed by  prokinetic drugs  to prevent recurrence if dysmotility is a suspected cause.


Symptoms traditionally linked to SIBO include  bloating ,  diarrhea ,  constipation , and abdominal pain/discomfort.  Steatorrhea  may be seen in more severe cases. [ 4 ]


Bacterial overgrowth can cause a variety of  symptoms , many of which are also found in other conditions, making the  diagnosis  challenging at times. [ 4 ]  Many of the symptoms are due to  malabsorption  of nutrients due to the effects of bacteria which either metabolize nutrients or cause inflammation of the small bowel, impairing absorption. The symptoms of bacterial overgrowth include  nausea ,  flatus , [ 5 ]   constipation , [ 6 ]  bloating, abdominal distension, abdominal pain or discomfort, diarrhea, [ 7 ]  fatigue, and weakness. SIBO also causes an increased  permeability of the small intestine . [ 8 ]  Some patients may lose weight. Children with bacterial overgrowth may develop  malnutrition  and have difficulty attaining  proper growth .  Steatorrhea , a sticky type of diarrhea where  fats  are not properly absorbed and spill into the stool, may also occur. [ 5 ]


Patients with bacterial overgrowth that is longstanding can develop complications of their illness as a result of malabsorption of nutrients. [ 9 ]  Laboratory test results may include elevated   folate  (vitamin B 9 ), and, less commonly,  vitamin B 12  deficiency or other nutritional deficiencies. [ 4 ]   Anemia  may occur from a variety of mechanisms, as many of the nutrients involved in production of  red blood cells  are absorbed in the affected small bowel.  Iron  is absorbed in the more proximal parts of the small bowel, the  duodenum  and  jejunum , and patients with malabsorption of iron can develop a  microcytic anemia , with small red blood cells. Vitamin B 12  is absorbed in the last part of the small bowel, the  ileum , and patients who malabsorb vitamin B 12  can develop a  megaloblastic anemia  with large red blood cells. [ 5 ]


In recent years, several proposed links between SIBO and other disorders have been made. However, the usual methodology of these studies involves the use of  breath testing  as an indirect investigation for SIBO. Breath testing has been criticized by some authors for being an imperfect test for SIBO, with multiple known false positives. [ 10 ]