CANCER OF CORPUS II—HISTOLOGY AND EXTENSIONThe majority of uterine cancers have a relatively well-differentiated glandular architecture. In general, of course, the more anaplastic tumors may be expected to grow more rapidly and to metastasize earlier than do the more mature adenocarcinomas. The differentiation between well-differentiated uterine adenocarcinoma and atypical, adenomatous hyperplasia of the endometrium is not simple, and often ﬁxed and stained rather than frozen sections must be obtained before submitting the patient to the treatment established for an ascertained malignancy.
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Celiac disease, also known as gluten-sensitive enteropathy or nontropical sprue, is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten. The primary target of the disease is the small intestine; celiac disease can affect multiple systems, however.
|CELIAC DISEASE AND MALABSORPTION|
It is primarily seen in individuals of European descent but is increasingly recognized on almost every continent. The overall prevalence in the general population of the United States and Europe is nearly 1%; only 10% to 15% of patients have been diagnosed and treated, however. The prevalence appears to increase with age. Celiac disease develops in genetically predisposed individuals as a result of the influence of environmental factors. First-degree relatives of patients with celiac disease have a 10% to 15% risk of developing the disease. The HLA class II genes HLA-DQ2 and HLA-DQ8, which are normally expressed on the surface of antigen cells in the gut, are the most important genetic susceptibility factors in celiac disease. HLA-DQ2 is found in 90% to 95% of patients with celiac disease, with HLA-DQ8 found in most of the remaining patients. These molecules are necessary variables predisposing a patient to the disease, which means that celiac disease is unlikely if neither molecule is present. The molecules are not, however, sufficient to cause celiac disease; they occur in 30% to 40% of the general population. Gluten is a storage protein of wheat. The alcohol-soluble fraction of gluten, gliadin, is toxic in celiac disease, along with similar proteins in barley (hordeins) and rye (secalins). These proteins are rich in glutamine and proline residues that even the healthy human intestine cannot fully digest. As a result, intact gliadin peptides are left in the lumen, but few cross the intestinal barrier. In individuals with celiac disease, these fragments come into contact with tissue transglutaminase, a ubiquitous intracellular enzyme that is released by inflammatory and endothelial cells and fibroblasts in response to mechanical irritation or inflammation. Upon contact, tissue transglutaminase cross-links with these glutamine-rich proteins and deamidates them. This process modifies glutamine residues into glutamic acid residues, which are ideally suited to interact with the HLA-DQ2 or HLA-DQ8 molecules. Once bound to HLA-DQ2 or HLA-DQ8, gliadin peptides are presented to the CD4+ T cells, triggering the inflammatory reaction. The end result is an inflammatory state of the small intestine, causing a derangement in the architecture of the mucosa, with flattening of the villi, and infiltration of lymphocytes into the epithelium.
Diverticula of Small Intestine
A diverticulum is a blind outpouching of a hollow viscus, consisting of one or more layers of the part involved. Small intestinal diverticula usually occur in the duodenum and occur less frequently in the jejunum and ileum. The true incidence is not known, because diverticula may remain asymptomatic and the diagnosis is usually incidental; duodenal diverticula have been reported in 7% of those undergoing endoscopic retrograde cholangiopancreatography. In about 20% of cases, they are associated with diverticula in other parts of the digestive tract.
Diverticula of the small intestine may be single or multiple. Jejunal diverticula are usually multiple and are frequently associated with disorders of intestinal motility, such as progressive systemic sclerosis, visceral neuropathies, and myopathies. The multiple diverticula can be so numerous as to involve nearly the entire small intestine. They are located almost always along the line of mesenteric attachment, with sizes varying from a few millimeters up to several centimeters in diameter. The “complete” diverticula, formed by all the layers of the intestinal wall, are believed to be of congenital origin and are frequently associated with other malformations. The “incomplete” diverticula, consisting only of mucosa and serosa, are caused by herniation through a defect caused by the entrance of large vessels.
The vitelline, or omphalomesenteric, duct connects the yolk sac with the primitive tubular gut in the early embryonic stages and normally involutes at about the 7th week of fetal life, leaving no trace of its existence. Failure of the vitelline duct to disappear in its entire extension results in a variety of remnants, which include a diverticulum (Meckel diverticulum) attached to the ileum, omphalomesenteric cysts (enterocysts), omphalomesenteric fistulae that drain through the umbilicus, and fibrous bands from the diverticulum to the umbilicus that predispose to bowel obstruction. The most common form is Meckel diverticulum.
|VARIANTS OF VITELLINE DUCT REMNANTS|
Meckel diverticulum is the most frequent congenital anomaly of the gastrointestinal tract and is classically described by the rule of twos. It is prevalent in approximately 2% of the population, is usually located within 2 feet of the ileocecal valve, and measures approximately 2 inches in length. It is two times as prevalent in males as in females, with approximately 2% of patients developing a complication, usually within the first 2 years of life. This diverticulum is always attached to the antimesenteric side of the ileal wall, and it varies in length (from 1 to 10 cm) and also in width (from 1 to 4 cm in diameter), though its shape usually resembles that of a finger of a glove. The artery supplying the diverticulum, the vitelline artery, is a branch of the superior mesenteric artery. It crosses over the ileal wall along the diverticulum to its tip.
Duplications of Alimentary Tract
Alimentary tract duplications, also referred to as mesenteric cysts, giant diverticula, or enteric cysts, are rare congenital malformations that develop during fetal life. These spherical or tubular structures may be single or, more frequently, multiple, and are equipped with all the layers of that part of the alimentary tract to which they are intimately attached, including the muscular coat. This is in distinction to diverticula, which lack a muscular coat. Gastrointestinal duplication cysts may or may not communicate with the adjacent lumen of the gastrointestinal tract.
Most intestinal duplications are diagnosed in newborn infants and children, but some can remain silent and present in adulthood. With the routine use of prenatal ultrasound, however, many are being diagnosed in utero. Associated anomalies are present in one third of cases and involve the spine and gastrointestinal tract.
An omphalocele, or exomphalos, is a midline abdominal wall defect covered by a membrane of amnion and peritoneum containing bowel, and, occasionally, spleen and liver at the base of the umbilical cord. When the defect is less than 4 cm, it is termed a hernia of the umbilical cord; when it is greater than 10 cm, it is termed a giant omphalocele. It results from the persistence of the physiologic midgut herniation beyond the 12th postmenstrual week. Associated abnormalities occur in 30% to 70% of infants and include chromosomal abnormalities (trisomy 13, 18, 21), congenital heart disease, Beckwith- Wiedemann syndrome, and prune belly syndrome. The diagnosis of an omphalocele can usually be made by inspection, but if the omphalocele is small, it may appear to be a normal part of the umbilical cord. The major differential diagnosis to consider is gastroschisis. Gastroschisis is a defect in the abdominal wall that usually occurs to the right of the normal insertion area of the umbilical cord; it is believed to arise at the site of involution of the right umbilical vein. The absence of a membranous sac with free-floating loops of bowel distinguishes gastroschisis from omphalocele; if the membranous sac of the omphalocele ruptures in utero, however, other clues should be sought, such as the location of the liver and site of the cord insertion. When omphalocele is identified prenatally, fetal genetic studies, including amniocentesis and fetal echocardiography, should be offered because of the high risk of aneuploidy and other congenital and genetic disorders. Fetal growth should subsequently be monitored closely. Precluding other obstetric indications, spontaneous labor and delivery should be allowed to occur.
Intussusception occurs when a proximal segment of the bowel telescopes into an adjacent distal segment. It is one of the most common abdominal emergencies in children but is rare in adults. Intussusception commonly occurs near the ileocecal junction, where the intussusceptum telescopes into the intussuscipiens, dragging the associated mesentery with it. This leads to the development of venous and lymphatic congestion with resulting intestinal edema, which can ultimately lead to ischemia, perforation, and peritonitis. Rarely, the proximal bowel is drawn into the lumen of the distal bowel (retrograde intussusception); this phenomenon is seen in Roux-en-Y gastric bypass surgery. The majority of cases in children are idiopathic, although evidence points to a preceding viral infection triggering the intussusception in some of these cases. On the other hand, adults usually have a distinct underlying pathologic lead point, which can be malignant in half of cases. Intermittent abdominal pain is the most common presentation in both children and adults. Symptoms progress over time and are accompanied by nausea and vomiting. In children, a sausage- shaped abdominal mass may be felt in the right side of the abdomen accompanied by the “currant jelly” stool mixed with blood and mucous.
|SITES OF DIAPHRAGMATIC HERNIAS AND HERNIATION OF ABDOMINAL VISCERA|
Diaphragmatic hernia in the newborn is a not uncommon defect and seems to be reported increasingly, in one to four neonates per 10,000 births. This probably reflects earlier diagnosis and more prompt treatment rather than increased incidence. If the diaphragmatic defect is not surgically repaired, most of these infants die within the first month of life as a result of respiratory compromise.
Congenital Intestinal Obstruction: Meconium Ileus
The condition known as meconium ileus develops exclusively in infants born with cystic fibrosis, which is a lethal autosomal recessive disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This mutation primarily interferes with chloride transport in various acinar structures of the intestinal, bronchial, salivary, and sweat glands, as well as those of the pancreas. Pancreatic damage can occur in utero; 85% to 90% of these patients develop severe pancreatic insufficiency. Subsequently, the meconium becomes thick and tenacious, adhering to the intestinal mucosa and causing impaction in the ileum and intestinal obstruction.
Congenital Intestinal Obstruction: Intestinal Atresia, Malrotation of Colon, Volvulus of Midgut
Intestinal obstruction in newborn infants is caused by a variety of congenital anomalies, and prompt diagnosis and treatment can be life-saving. The causes of such intestinal obstructions may be atresia of the esophagus, diaphragmatic hernia, annular pancreas, malrotation of the colon with volvulus of the midgut, peritoneal bands mostly compressing the duodenum, internal or mesentericoparietal herniations, meconium ileus, aganglionic megacolon, imperforate anus, and atresia or congenital stenosis of the bowel.
|CONGENITAL INTESTINAL ATRESIA|
Atresia refers to the complete congenital obstruction of the lumen of a hollow viscus, and stenosis refers to luminal narrowing of varying degrees. The most common site of intestinal atresia is the small bowel, particularly the jejunum and ileum; the colon is least commonly affected. Intestinal atresia results from an interruption in the normal development of the gastrointestinal tract, commonly during the second and third months of fetal life. In the proximal small bowel, this is often caused by failure of the intestine to recanalize. As the intestine changes from a solid structure to a hollow tube, one or more septa may persist, leaving a diaphragm of tissue with only a minute opening and setting up a stenosis. If such persisting septa leave an intact diaphragm across the lumen, or if, during the solid stage, the intestine divides to form two or more blind segments entirely separate from each other or connected by threadlike fibrous bands, atresia ensues. In the middle and distal small bowel, atresia often results from vascular disruption, leading to ischemic necrosis of the fetal intestine. Because the fetal bowel is sterile, the necrotic tissue is resorbed, leaving blind proximal and distal ends, often with a gap in the mesentery.