1. Pathology of gastrointestinal tract I MUDr. Helena Skálová - Esophagus - Stomach

2. Esophagus 25 cm Wikibooks

3. Inborn defects Atresia Tracheoesophageal fistula Robbins and Contran Pathologic Basis of Disease, 7th edition

4. Motoric dysfunction of esophagus Achalasia: -loss of cells in plexus myentericus -loss of peristalsis -inability od lower eosphageal sphincter to relax -megaesophagus Hiatal hernia: -widening of hiatus diaphragmaticus -displacement of GE junction and part of stomach to dorsal mediastinum -sliding, paraesophageal, mixed Robbins and Contran Pathologic Basis of Disease, 7th edition

5. Diverticules: -Zenker – FE junction -tractional – postinflammatory fixation to LN -epiphrenic – defective coordination of peristalsis and relaxation of sphincter Mallory-Weiss syndrome: -laceration of distal esophagus and GE junction -risk of bleeding, rarely perforation -after strong vomiting Robbins and Contran Pathologic Basis of Disease, 7th edition Motoric dysfunction of esophagus

6. Esophageal varices Portal hypertenzion (90% pacients with cirrhosis, e.g. alcoholic) Portocaval anastomoses → varices in submucosa of terminal esophagus Asymptomatic → rupture → massive hematemesis 40-50% mortality in each episode 50% rebleeding Therapy: varix sclerotization, baloon tamponade

7. Esophagitis 5% adult population Etiology: -Gastroesophageal reflux disease -Consumption of strong iritants (acids, lyes, alcohol + smoking, hot liquids) -Infection – immunosupressed pacients (HS, CMV, candida, aspergilus)

8. Reflux esophagitis (= gastroesophageal reflux disease) Reflux of acidic gastric content into distal esophagus over insufficient lower sphincter -decreased tonus of the sphincter (pregnancy, calming drugs alcohol + smoking) -sliding hiatal hernia Adults > 40 y.o., children Symptoms: heart burn (chest pain), dysphagia, regurgitation of acidic gastric content → cough Micro: chronic inflammation in distal esophagus, Barrett esophagus

9. Barrett esophagus 10% pacients with longterm symptomatic GE reflux 40-60 years old, white men Response to longterm irritation → intestinal metaplazia Precancerosis: Dysplazia → adenocarcinoma (30-40x higher risk)

10. Tumors of esophagus BenignMalignant Leiomyoma Fibroma, lipoma, hemangioma … Squamocellular papiloma Squamocellular carcinoma Adenocarcinoma Prognosis: bad, high mortality Gross: exophytic, flat, ulcerated Symptoms - late: dysfagia, obstruction, bleeding, weight loss

11. Adenocarcinoma Carcinoma of distal esophagus in 10% pacients with Barrett esophagus Symptoms include heart burn Median 60 y.o., white men Higher incidence: developed countries Micro: glandular mucous producing intestinal-type carcinoma Invasion to stomach, mediastinum Metastases in regional LN

12. Sqamocellular carcinoma Whole esophagus, mainly upper 2/3 Adults, > 50 y.o., men Higher incidence: developing countries RF: alcohol, smoking Invasion into surrounding structures (trachea, aorta, mediastinum, pericardium …) Metastases in regional LN

13. Stomach

14. Gastritis = inflammation of gastric mucosa  Symptoms: -dyspepsia of upper type, pain in epigastrium, nausea, vomiting, haematemesis, melaena -chronic often asymptomatic  Histological evaluation necessary  2 types: -Acute -Acute (neutrophils, haemorrhage, erosions) -Chronic -Chronic (lymocytes, plasma cells + neutrophils in acute relaps)

15. Acute gastritis  Haemorrhagic, erosive  Risk factors - etiology: -NSAID (Aspirin) -Alcohol, smoking -Acid burn (suicide attempt) -Stress (shock, trauma, burns, surgery, sepsis)  Complications: haemoptysis (also massive), melaena  Common disease  25% pacients using aspirin daily (rheumatoid arthritis)  Gastropathy – irritation, erosions or mucosal bleeding without inflammation, may precede gastritis

16. Chronic gastritis  Atrophy, hypertrophy  Intestinal metaplazia  Dysplazia  RF for gastric cancer  Etiology: -Helicobacter pylori - B -Autoimmune - A -Toxic (alcohol, smoking) - C

17. Helicobacter pylori Nonsporulating Gram- rod 1983 Campylobacter pyloridis Specialization for life in stomach: -Flagellum -Ureasis (urea → CO ₂ + NH ₃ ) -Expression of bacterial adhesins -Expression of bacterial toxins → peptic ulcer Antral gastritisAntral gastritis, ↑ secretion of HCl → peptic ulcer PangastritisPangastritis, ↓ secretion of HCl, RF for ca Association: - chronic gastritis, peptic ulcer - gastric carcinoma and lymphoma (MALT) Therapy: antibiotics, inhibitors of proton pump

18. Autoimmune gastritis ‹ 10% gastritides Autoantibodies angainst parietal cells (e.g. receptor for gastrin, intrinsic factor) Destruction of glands, atrophy of mucosa → ↓ production of HCl and intrinsic factor Malabsorption of vitamin B12 Pernicious anemia: -megaloblastic anemia -demyelinization of dorsolateral tracts (motoric and senzoric) -Hunter glossitis RF for carcinoma, carcinoid

19. Peptic ulcer Gastroduodenal ulcer disease Etiology: H. pylori, ischemia, NSAID, alcoholic liver cirrhosis H. pylori: 100% duodenal, 70% gastric (ulcer in 10-20% infected patients) Chronic, solitary lesion, relapsing, spontaneously healing Duodenum, antrum and lesser curvature ( ↑ HCl) Adults, more men Symptoms: - Pain 1-3 hrs after meal and in the night, relief after meal - Nausea, vomiting, flatulence, weight loss Dif. dg.: CARCINOMA!!! Zollinger-Ellison syndrome – gastrinoma (NET usually in pancreas, duodenum)

20. Acute ulcer NSAID Stress ulcers – shock Pathogenesis uncertain, role of ischemia

21. Complications of gastric ulcer Bleeding - 15-20% pacients, 1/4 † Perforation, penetration - 5% pacients, 2/3 † Stenosis by edema and strictures -2% pacients -pylorus, duodenum

22. Tumors of stomach Benign Malignant  Adenoma  Leiomyoma Carcinoma (93%) Lymphoma (4%) GIST (2%) NET = carcinoid (3%) Polyps Hyperplastic polyp Fundic gland polyp

23. Stomach carcinoma  One of the most frequent worldwide ( ↑↑↑ Japan)  High mortality, decrease from 60‘ (endoscopy)  M:W = 2:1  RF: H. pylori (5-6x) – chronic gastritis, diet  Symptoms - late: ↓ weight, pain, anorexia, vomiting, haemorrhage, anemia  2 main histological types: - Intestinal (resambles intestinal adenocarcinoma) - Diffuse (poorly differenciated, often with signet-ring cells) !

24. Stomach carcinoma  Early  Advanced  Local invasion: duodenum, pancreas, retroperitoneum  Metastases: region and distant LN (Virchowov), peritoneal spread, liver, lungs, ovaries (Krukenberg tumor)

25. Other malignant gastric tumors  Lymphoma (MALToma, low grade) -H. pylori (regression after atb elimination) -mucosa, submucosa -symptoms: nonspecific (nausea, dyspepsia)  GIST -Cajal cells -solitary, multiple -30% malignant (abdominal spread, distatnt metastases)  Neuroendocrine tumor = carcinoid

26. Stomach NET (neuroendocrine tumor) Neuroendocrine tumor (NET) Neuroendocrine carcinoma (NEC) Predisposition: Autoimmune chronic atrophic gastritis MEN1 (syndrome of multiple endocrine neoplasia) Zollinger-Ellison syndrome – gastrinoma (NET usually in pancreas, duodenum) Solitary, multiple Small tumor Growth in deep LPM and submucosa, covered by mucosa May produce serotonin, histamin, ATCH, gastrin …

27. Bleeding into gastrointestinal tract Hematemesis: -vomiting of blood -from upper GIT (oral cavity, esophagus, stomach) Melaena: -digested (black) blood in stools -from upper GIT (oral cavity, esophagus, stomach) Enterorrhagia: -fresh (red) blood in stools -from lower GIT (intestines, anus) Other symptom: anaemia

28. Differential diagnosis: Hematemesis and melaena Oesophagus -Varices -Reflux oesofagitis -Oesophageal carcinoma -Sy Mallory-Weiss -Rupture of aortal aneurysm -Acid burns -Foreign body Oesophagus -Varices -Reflux oesofagitis -Oesophageal carcinoma -Sy Mallory-Weiss -Rupture of aortal aneurysm -Acid burns -Foreign body Stomach -Varices of gastric carcia -Gastritis (aspirin, alcohol) -Ulceration (incl. Zollinger-Ellison sy) -Stomach carcinoma -Vascular malformation -Complication of endoscopy Stomach -Varices of gastric carcia -Gastritis (aspirin, alcohol) -Ulceration (incl. Zollinger-Ellison sy) -Stomach carcinoma -Vascular malformation -Complication of endoscopy Duodenum -Ulceration -Tumor -M. Crohn -Penetration of bile stone into duodenum -Acute hemorrhagic-necrotizing pancreatitis Duodenum -Ulceration -Tumor -M. Crohn -Penetration of bile stone into duodenum -Acute hemorrhagic-necrotizing pancreatitis Other: -Hemorrhagic diathesis -Trauma -Hemoptysis -Bleeding from oral cavity Other: -Hemorrhagic diathesis -Trauma -Hemoptysis -Bleeding from oral cavity

29. Differential diagnosis: Enterorrhagia Hemorrhoidal varices Diverticulosis Ulcerative colitis, Crohn disease Bacterial enterocolitis Carcinoma, larger adenoma Iatrogenous (after polypectomy, postradiation, NSAID …) Hemorrhoidal varices Diverticulosis Ulcerative colitis, Crohn disease Bacterial enterocolitis Carcinoma, larger adenoma Iatrogenous (after polypectomy, postradiation, NSAID …)

30. Summary Esophagitis: -reflux → chronic inflammation → intestinal metaplasia → adenocarcinoma Esophageal tumors: -adenocarcinoma, squamous carcinoma -bad prognosis Helicobacter pylori: -chronic gastritis, peptic ulcer, stomach adenocarcinoma, lymphoma Stomach tumors: -adenocarcinoma (intestinal, diffuse) Bleeding into GIT: -hematemesis, melaena, enterorrhagia, anaemia -upper, lower GIT, adjacent structures