Stomach and duodenumTeaching slides

Stefano Fiorucci, MD

University of Perugia

Department of Surgery and Biomedical Sciences

Istologia

Radiologia

Gastric Glandular Morphology

Composition of the Gastric Juice

p.282

Gastric HCl Secretion

Proton Pump

(H,K-ATPase)

Na+ Pump

(Na,K-ATPase)

ATP

p.282A protective role for mucus

Gastritis

Gastritis is an inflammation of the stomach lining.

can be caused by infection, irritation, autoimmune disorders (where the body' s immune system mistakenly attacks the stomach), or backflow of bile into the stomach (bile reflux). Gastritis can also be caused by a blood disorder called pernicious anemia.

GastritisGastritis is an inflammation of the stomach lining.

• Infections can be caused by:

• Bacteria (usually Helicobacter pylori)

• Virus (including herpes simplex virus)

• Parasite

• Fungus

• Long term use of NSAIDs, such as ibuprofen or naproxen

• Alcohol use

• Cigarette smoking

• Chronic vomiting

• Coffee and acidic beverages

• Too much stomach acid (such as from stress)

• Eating or drinking caustic or corrosive substances (such as poisons)

Gastritis

Acute

• Erosive gastritis is a gastric mucosal erosion caused by damage to mucosal defenses. Alcohol erodes the mucosal lining of the stomach; low doses of alcohol stimulate hydrochloric acid secretion. High doses of alcohol do not stimulate secretion of acid.

• NSAIDs inhibit cyclooxygenase-1, or COX-1, an enzyme responsible for the biosynthesis of eicosanoids in the stomach, which increases the possibility of peptic ulcers forming. Also, NSAIDs, such as aspirin, reduce prostaglandin.

Gastritis

• Chronic

• Chronic gastritis refers to a wide range of disorders of the stomach including:

- Autoimmune gastritis

- Reflux (bile) induced gastritis

- Helicobacter pylori associated gastritis

- NSAIDs induced gastritis

- Crohn’s gatsritis

The Nobel Prize in Physiology or Medicine 2005 Barry J. Marshall, J. Robin Warren

Helicobacter pylori• Attachment:• The Helicobacter pylori enter the stomach and attach to

the protective mucus lining of the stomach wall. The bacteria are able to survive in the strongly acid environment of the stomach because they excrete the enzyme urease which neutralized the acidic environment of the stomach by converting urea into the basic ammonia and buffer bicarbonate. Inside the mucus lining of the stomach wall, the bacteria cannot be killed by the bodies immune system.

• Toxin production:• The Helicobacter pylori produce toxins such as

vaculating cytotoxin A (VAC A) that cause the cells in the lining of the stomach to die. This allows the bacteria to better access of nutrients as it decreases the competition from stomach lining cells.

• Cell Invasion:• The bacteria invade the protective inner lining of the

stomach so that they can be protected from immune system. The bacteria then kill the cells that they invade which creates holes in the mucus lining of the stomach, causing the formation of ulcers. Additionally, the substances released by the bacteria during the invasion, hurt the stomach cells ability to absorb calories from food in the stomach.

Consequences of H. pylori infection

Fig. 2 Progression of <ce:italic> H. pylori</ce:italic> -related diseases in stomach and duodenum as related to life stages. Clinical appearance of diseases occurs in mid-life resulting in severe degenerative conditions only in advanced age in a ...

Diagnosi

Biopsia gastrica

Breath test

Ricerca anticorpi (sangue o campioni fecali)

Terapia eradicante

• Terapia antibiotica e IPP

Omeprazolo/pantoprazolo/esomeprazolo

Claritromicina

Amoxicillina

Levofloxacina

metronidazolo

Progression to intestinal-type gastric cancer. H. pylori infection leads to superficialgastritis over a period of weeks. The presence of proinflammatory host

polymorphisms and the H. pylori cag pathogenicity island increase the risk of developing gastric atrophy, intestinal metaplasia, and gastric adenocarcinoma. Epigenetic inactivation of E-cadherin via promoter hypermethylation may also

contribute to intestinal-type gastric cancer.

Gastric cancer staging

• Primary tumor (T):Tis = carcinoma in situ: intraepithelial tumor without invasion of lamina propria T1 = tumor invades lamina propria or submucosaT2 = tumor invades muscularis propria or subserosaT3* = tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structuresT4**,*** = tumor invades adjacent structures

• *A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepaticligaments or into the greater or lesser omentum without perforation of the visceral peritoneum. **Structures adjacent to the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. ***Intramural extension to the duodenum or esophagus is classified by the depth of greatestinvasion in any of these sites, including the stomach).

• Regional lymph nodes (N):Include the perigastric nodes along the lesser and greater curvatures, and the nodes along the leftgastric, common hepatic, splenic, and celiac arteries. N0 = no regional lymph node metastasisN1 = metastasis to 1–6 regional lymph nodesN2 = metastasis in 7–15 regional lymph nodesN3 = metastasis in more than 15 regional lymph nodes

• Distant metastasis (M):M0 = no distant metastasisM1 = distant metastasis

Endoscopic treatment

Gastric cancer surgery

Chemotherapy

•ADENOCARCINOMA of the stomach is relatively sensitive to chemotherapy

• Fluorouracil (5-FU) is the most commonly used drug in the treatment of gastric cancer, with a response rate around 21%. In an attempt to improve this rate, drug combinations have been tried; the most common is 5-FU, doxorubicin, and mitomycin C (FAM) with a response rate of 33% and an acceptable degree of toxicity .Other drug combinations have been tried, although the response duration and overall survival, when compared with 5-FU alone, were not significantly different. In addition, the combination groups had a higher toxicity rate. Newer investigational modalities employ tumor antigen-specific immunochemotherapy. Antibodies to tumor antigens are conjugated with chemotherapeutic drugs; in this way, the drugs can be delivered to the tumor directly.

Endoscopic palliation