PEPTIC AND OTHER BENIGN ULCERS

Avvertenza per gli studenti del corso di Anatomia Patologica del corso Integrato Malattie dellapparato Gastroenterico e Infettive.

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Achille PICH

Peptic ulcer can occur wherever mucosa is bathed by gastric secretion. This includes the stomach, duodenum, lower third of esophagus, margin of a gastrojejunostomy, and Meckel's diverticulum with ectopic gastric mucosa.

Acid peptic digestion is the ultimate cause for ulceration, but the mechanisms that render the mucosa susceptible to this digestion are just as important for the pathogenesis.

Duodenal ulcers (which are more common than gastric ulcers) are associated with acid hypersecretion, but most patients with gastric ulcer secrete either low normal or below normal amounts of acid. 1)This injury may be mediated by reflux of bile and pancreatic juice and is manifested anatomically by the presence of gastritis. 2) Helicobacter pylori plays an important role in the pathogenesis of this disease. The risk for the development of a peptic ulcer is approximately 10x in H. pyloripositive gastritis than in a normal stomach, and the risk is increased further (2-3x) when there is antral atrophy. Thus it would seem that the initial event in gastric ulcer is mucosal injury, which renders it more susceptible to acid peptic damage.

In patients with GU, defective mucosal resistance to autodigestion is of prime importance. In patients with DU, the aggressive action of increased acid and pepsin is of prime importance.

Location: GU: lesser curvature; antrum DU: 90% are in the first portion

Pyloric ulcers behave like duodenal ulcers. DU is 4 times more frequent than GU. 10-20% of patients with peptic ulcers have both GU and DU.

The cause of peptic ulcer is multifactorial and may involve any factor that regulates acid secretion and the defense against autodigestion. Causal factors differ somewhat in gastric peptic ulcer (GU) and duodenal peptic ulcer (DU).

GU DU

acid normal or low acid high gastric stasis rapid gastric emptying Helicobacter pylori Helicobacter pylori chronic gastritis abnormal duodenal motility pyloric reflux decreased duodenal bicarbonate aspirin, alcohol, drugsincreased blood group O increased back diffusion of H-ionsincreased parietal cell mass mucosal ischemia psychological stress + low socio-economic scale high socio-economic scale

ACUTE GASTRIC ULCER

debilitating illness sepsis surgery or trauma (stress ulcer)central nervous system injury or disease (Cushing's ulcer)long-term steroid therapy (steroid ulcer)aspirin ingestionextensive burns (Curling's ulcer)radiation therapy or hepatic arterial chemotherapyintroduction of tubes into the stomach

If the ulcer involves only the mucosa (a process usually designated as erosion), it can heal completely, but if part of the muscle is destroyed, it is replaced by fibrotic tissue, leaving a depressed pit.

Any of these ulcers, if deep enough, may perforate; this complication is particularly common in ulcers induced by radiation therapy.

CHRONIC PEPTIC ULCER

Always occurs in an achlorhydric zone of mucosa (i.e., an area of stomach lined by pyloric-type mucosa). Up to 95% of the ulcers are located on the lesser curvature (so-called Magenstrasse) near the incisura angularis; however, since chronic gastritis is accompanied by antral metaplasia of the fundal mucosa that advances proximally from the pylorus, peptic ulcer can be found anywhere in the stomach, although it is always surrounded by antral-type mucosa.

The average age at the time of diagnosis is 50 years, but the disease can occur at any age group. A male predilection exists but seems to be decreasing. About 5% of the ulcers are multiple. The radiographic diagnosis is about 95% accurate, but atypical cases cannot be distinguished with certainty from carcinoma. Although some controversy persists, most authors believe that ulcers of giant size (over 3 cm) or those located in the greater curvature do not indicate a high likelihood of malignancy, as formerly believed. The diagnosis of peptic ulcer has been greatly facilitated by the use of fiberoptic gastroscopy, which allows the endoscopist to have a direct view of the ulcer, and to obtain biopsies from the edges; multiple (about ten) biopsies are recommended for the standard-size ulcer.

Grossly, an active lesion is sharply delineated, usually oval or round but sometimes linear, with converging mucosal folds extending to its margin.

Sharply delimited chronic peptic ulcer with converging folds of mucosa in the upper half. The ulcer bed is covered by fibrinopurulent exudate.

Entire thickness of muscular layer has been destroyed Mariuzzi. Anatomia Patologica. Piccin Nuova Libraria S.p.A On section, there is undermining of the edges (especially on the proximal side) and complete replacement of the muscle wall by grayish white fibrous tissue. On the serosal side, there may be subserosal fibrosis and inflammatory enlargement of the regional lymph nodes.

Prominent marginal nodularity about the ulcer should suggest the presence of carcinoma; however, it should be remembered that in some instances it is impossible to distinguish grossly a peptic ulcer from an ulcerated carcinoma. As a matter of fact, about 10% to 15% of gastric carcinomas appear grossly to be benign ulcers.Peptic ulcers can be classified according to: 1) shape and size (round-oval, giant, linear)2) activity (open ulcers or ulcer scars) 3) depth of penetration (submucosa, muscularis externa, or beyond), or a combination of these criteria.

Microscopically, an active, well-developed, chronic peptic ulcer will show four more or less distinct layers: (1) a surface coat of purulent exudate, bacteria, and necrotic debris (2) fibrinoid necrosis (3) granulation tissue (4) fibrosis replacing the muscle wall and extending into the subserosa . At the edges, the muscularis mucosae is seen to fuse with the muscularis externa. Other common features in the ulcer bed include thickening of vessels caused by subendothelial fibrous proliferation and hypertrophy of nerve bundles; both of these changes are probably secondary events. The necrotic surface may show superimposed infection by Candida albicans.

Note the total interruption of the muscle wall, replacement by fibrous tissue, overhanging appearance of the mucosa on the proximal side, and ladder-like (scala) configuration on the distal (left) side ProximalDistal

(1) necrotic debris(2) fibrinoid necrosis(3) granulation tissue

In the healing process of a peptic ulcer, regenerating epithelium grows over the surface. This epithelium often exhibits features of intestinal metaplasia and may contain chief and parietal cells when the ulcer is located in the fundic area. The presence of irregularities in its deep portion should not be misinterpreted as carcinoma. The danger of overdiagnosis is particularly great in the ulcers caused by arterial infusion chemotherapy because of the marked epithelial atypia that may be present.

Complications of ulcers 1 bleeding (20%) 2 perforation (5%) 3 obstruction (10%)4 - development of carcinomas (rarely 1%, only in the stomach)

TreatmentThe medical treatment of gastric ulcer consists of antacids and/or H2-blockers.The usual criterion for adequate healing is a reduction in crater size of at least 50% over a 6- to 8-week period of intensive medical management. Failure to pass this test, development of complications (hemorrhage, perforation, obstruction), and recurrence of the ulcer are indications for surgery. Giant ulcer size (over 3 cm) is another quoted indication, although medical therapy can also be successful in these cases. It should be remembered that as many as 15% of gastric carcinomas may pass the "healing test" and that some benign ulcers may actually enlarge during the test.

The surgical procedures in general use for peptic ulcer are subtotal gastric resection without vagotomy, truncal vagotomy and drainage (either gastroenterostomy or pyloroplasty), and truncal vagotomy plus antrectomy. When a portion of stomach is removed, continuity is reestablished through a gastroduodenostomy (Billroth I) or gastrojejunostomy (Billroth II). The long-term results of surgery are good to excellent in over 80% of the patients

Vagotomia selettiva: prevede la sezione dei due nervi vaghi subito al disotto della loro divisione nel ramo extra-gastrico, che viene risparmiato, e nel ramo gastrico che viene interrotto. In tal modo si evitano alcune delle conseguenze della vagotomia tronculare (atonia dello stomaco che si dilata enormemente, alterazioni della secrezione pancreatica e biliare con predisposizione alla formazione di calcoli, atonia intestinale, reflusso esofageo, diarrea) ma persistono la atonia gastrica e la difficolt di svuotamento dello stomaco.A questo inconveniente si cerc di porre rimedio associando alla vagotomia la contemporanea piloro-plastica, o antrectomia

DUODENAL PEPTIC ULCER

It remains a very common disease, although its incidence seems to be decreasing. Its pathogenesis is related to the interplay of aggressive factors (gastric juice eroding and digesting its way into the mucosa) and defensive factors (bicarbonate and intact epithelium). Gastric acid hypersecretion is the rule in these patients. Thus a preserved fundic mucosa in the stomach is a prerequisite for the formation of duodenal peptic ulcer, which is also thought to be associated with gastric metaplasia and an increased load of Helicobacter in the duodenum.

Grossly, duodenal peptic ulcer is usually single and within 2 cm of the pylorus, although it may also occur in the second portion of the duodenum. When the ulcer is in the latter position, it may be the source of upper abdominal pain and bleeding. When duodenal ulcers are multiple and randomly distributed in the proximal and distal portions of the duodenum, the possibility of Zollinger-Ellison syndrome should be ruled out. Peptic ulcer has well-defined margins sharply set off from the surrounding mucosa.

Microscopically, most microscopic features are analogous to those of its gastric counterpart. Gastric metaplasia is common. At times, a large vessel with an open lumen may be seen at the base of the ulcer. Fibrosis of a healed ulcer may produce secondary diverticula and considerable shortening of the duodenum. Chronic duodenitis is regularly present.

Peptic ulcer of the duodenum does not become malignant.

TreatmentWith current medical treatment using cimetidine or other drugs, 80% of the ulcers heal within a month. The refractory ulcers tend to occur in younger patients, to be larger, and to be associated with more severe duodenitis. About one in five duodenal peptic ulcers requires surgical therapy. Indications for surgery are complications, such as hemorrhage, perforation, and obstruction, and lack of response to medical therapy. The two standard surgical techniques currently performed are vagotomy with antrectomy and gastroenterostomy, and vagotomy with pyloroplasty. The gastric resection may not include the ulcer, and only in a few instances is complete excision of the ulcer performed.

MARGINAL ULCER

Is a type of peptic ulcer that appears at the site of a gastrojejunostomy opening. Although the ulcer may be at the stoma itself, in most instances it is located on the jejunum at some distance from the opening. It was a common complication at the time when gastro-enterostomy for duodenal peptic ulcer was being done without a concomitant gastric resection. It is still seen, although rarely, following gastroenteroanastomosis with gastric resection (Billroth II operation) for duodenal ulcer, especially if the entire antrum is not removed or if the afferent jejunal loop is of excessive length. Occasionally, marginal ulcer develops following gastric resection for peptic ulcer or cancer of the stomach.