Acute pancreatitis
Sudden inflammation and hemorrhaging of the pancreas due to the destruction by its own digestive enzymes (autodigestion). Etiology:- Biliary pancreatitis (e.g., gallstones, constriction of the ampulla of Vater) ∼40% of cases- Alcohol-induced (∼30% of cases)- Idiopathic (∼15%-25% of cases)- Hypertriglyceridemia, hypercalcemia- Post-ERCP- Toxic drugs (e.g., steroids, azathioprine, sulfonamides, protease inhibitors, NRTIs)- Viral infections (e.g., coxsackievirus B, mumps)- Trauma- Autoimmune and rheumatological disorders (e.g., Sjögren's syndrome)- Pancreas divisum- Hereditary (e.g., mutation of the trypsinogen gene, cystic fibrosis) Pathophysiology:1. Intrapancreatic activation of pancreatic enzymes2. Enzymatic autodigestion of pancreatic parenchyma3. Attraction of inflammatory cells Symptoms: - Nausea, vomiting, fever- Hypocalcemia (used up by fat necrosis)- Cullen's sign (bruising around belly button) and Grey Turner's sign (flank)- Diagnosis: Clincial (epigastric pain), lab data (amylase, lipase), imaging Treatment: Pain control, fluids, rest bowels (parenteral nutrition), oxygen, antibiotics as needed Complications:- Pseudocysts - Abscess - Internal bleeding from damages blood vessels → hypovolemic shock- Disseminated intravascular coagulation (DIC)- Acute respiratory distress sydrome (ARDS)- Prerenal failure due to volume depletion- Hypocalcemia
Akute Pankreatitis
1. Interstitielles Ödem 2. Disseminierte Fettgewebsnekrosen: Das Fettgewebe setzt im Rahmen der Nekrose Fettsäuren frei, die hämatoxylinblaue Kalkablagerungen (Fettkalkspritzer) bilden 3. Nekrose 4. Entzündliche Reaktion 5. Intravasale Gerinnung
Chronic pancreatitis
Perisistent, chronic inflammation of the pancreas, often due to repeated bouts of acute pancreatitis.Distict histopathology! → Irreversible changes to the pancreatic structure: Fibrosis, atrophy, calcification Causes: Alcohol, tumors, trauma, cystic fibrosis, autoimmune (Sjögren syndrome) - Ductal dilatation and damage to tissue- Stellate cells lay down fibrotic tissue → narrowing of ducts- Acinar cell atrophy- Accumulation of calcium deposits in ducts Diagnosis:- Lab may be normal (atrophic tissue, insufficiency)- X-rays and CT scans may show calcifications- ERCP can show ducts with subsequent fluoroscopy studies ("chain-of-lakes" pattern)- MRCP- Malabsorption syndrome: Weight loss, steatorrhea, vitamin deficiency (ADEK) Long-term consequences: - Diabetes mellitus- Pseudocysts- Pancreatic cancer
Chronische Pankreatitis
1. Entzündungsinfiltrat 2. Nekrosezonen 3. Atrophie/Verlust des Drüsengewebes 4. Fibrose 5. Anomalien des Gangsystems (Stenose, Dilatation) 6. Verkalkungen
Pancreatic cancer
- Age of onset: 60-80 years- More common in African Americans Risk factors: Smoking, obesity, high alcohol consumption, diet high in red meat, male gender, African American, age >65 years; diabetes, chronic pancreatits, liver cirrhosis; family history (BRCA2 mutation, PRSS1 gene mutation, Peutz-Jeghers syndrome) Clinical presentation:- Nausea, vomiting, fatigue, weight loss, midepigastric pain- Trousseau sign (Thrombophlebitis migrans)- Courvoisier sign: Nontender, palpable gallbladder- Jaundice, darker urine, lighter stools, pruritus- Impaired glucose tolerance Location:- Pancreatic head: 75% of cases- Pancreatic body: 15–20% of cases- Pancreatic tail: 5–10% of cases Types:- Pancreatic exocrine tumors (95%): → Ductal adenocarcinoma→ Acinar adenocarcinoma → Cystadenocarcinoma- Pancreatic endocrine tumors (Neuroendocrine tumors, < 5% of tumors)→ Insulinomas (result in hypoglycemia)→ Gastrinomas→ Vasoactive intestinal peptide-producing tumors (VIPomas), pancreatic polypeptide-secreting endocrine tumors of the pancreas, glucagonomas, somatostatinomas - Lab functions: ↑ Amylase, lipase, CA 19-9, CEA- Staging: (1) < 2 cm, (2) >2 cm, (3) invasing neighboring tissue, (4) metatatic Treatment: (Neo)adjuvant chemotherapy, surgery
Duktales Pankreasadenokarzinom
1. Tumorknoten: Kleindrüsig bis alveolärer Aufbau 2. Fibrose 3. Destruktives Wachstum, erhaltene endokrine Inseln 4. PAS-postives Material in den Tumorzellen 5. Nekrose
Serös-zystischer Pankreastumor
- F > M- Alter: 35-90 Jahre- Lokalisation: Korpus, Schwanz (50-65%) (vgl. Pankreaskarzinom im Kopf)- Assoziation mit von Hippel Lindau Syndrom (Hämangioblastom, Nierenzellkarzinom, Phächromozytom) - Zystischer Tumor mit einem Glykogen-reichen Epithel- Keine Beziehung zum Gangsystem Serös-zystischer Tumor → Seröses Zystadenom / Seröses Zystadenokarzinom Prognose: Sehr gut
Muzinös zystischer Pankreastumor
- F:M = 9:1- Alter: 20-80 Jahre- Lokalisation: Korpus, Schwanz (50-65%) - Zystischer Tumor mit einem zylindrischen schleimbildenden Epithel und ovariellem Stroma- Keine Beziehung zum Gangsystem Muzinös-zystisches Pankreastumor → Muzinöses Zystadenom / Muzinös-zystischer Borderline-Tumor / Muzinöses Zystadenokarzinom Prognosefaktor für einen schlechten Verlauf: Invasion
Intraduktaler papillär-muzinöser Tumor (IPMT)
- Männer und Frauen- Alter: 40-80 Jahre- Lokalisation: Haupt- und/oder grössere Seitengänge - Assoziation mit anderen Malignomen (30%): Kolon- und Magenkarzinom Intraduktal papillär-muzinöser Tumor (IPMT) → Adenom / Borderline-Tumor / Invasives Karzinom
Solider pseudopapillärer Tumor
- F:M = 9:1- Alter: 8-60 Jahre- Lokalisation: Korpus/Schwanz des Pankreas Prognose: sehr gut
Normaler Ösophagus
25-30 cm long tube from the pharynx to the stomach Histologie:- Mucosa:1. Nicht-verhornendes, mehrschichtiges Plattenepithel2. Lamina propria3. Muscularis mucosae (glatt)- Subserosa mit serösen Schleimdrüsen- Muscularis propria mit einer inneren zirkulären und einer äusseren longitudinalen Schicht (quergestreift obere 1/3, glatt untere 1/3, gemischt mitteleres 1/3)- Adventita Obere und untere esophageale Sphinkter
Esophageal cancer
Etiology:- Adenocarcinoma: Gastroesophageal reflux (Barrett's esophagus), obesity, smoking, achalasia→ Localization: Lower 1/3- Squamous cell carcinoma: Smoking, alcohol, diet low in fruit and vegetables, hot beverages, diverticula (eg, Zenkers), nitrosamine exposure, radiotherapy, Plummer-Vinson syndrome, esophageal candidiasis, achalasia→ Localisation: Upper 2/3 Symptoms: Dysphagia, weight loss, retrosternal chest or back pain, anemia Diagnostics:- Esophago-gastro-duodenoscopy (best initial and confirmatory test) + biopsiesStaging: - Transesophageal endoscopic ultrasound (infiltration depth and regional lymph node disease)- Chest and abdominal CT and/or PET Pathology:- Adenocarcinoma: often present with adjacent Barrett mucosa and high-grade dysplasia- Squamous cell carcinoma: Breakdown of uniform tissue structure, clusters with circular keratinization, lymphocytic infiltration between the carcinoma clusters Treatment:- Curative: → Endoscopic submucosal resection for removal of superficial, epithelial lesions → Subtotal or total esophagectomy with gastric pull-through procedure or colonic interposition→ Neoadjuvant chemoradiation- Palliative: Chemoradiation, stent placement
Esophagitis - Differential
- Gastroesophageal reflux disease → Reflux esophagitis → Symptoms: Heartburn, regurgitation, coughing, feeling of lump in throat→ Endoscopy shows signs of erosions: Classification with Savary-Miller system or Los Angeles system→ Treatment: PPIs for 8 weeks. If needed >6 months, then replaced with H2R-antagonists - Medication-induced esophagitis: NSAIDs, doxycycline, potassium chloride, bisphosphonates→ Few hours to weeks after intake→ Symptoms: GI bleeding, weight loss→ Endoscopy shows ulcers that are mainly in the middle of the esophagus, can be coated with medication→ Treatment: Stop medication, switch to liquid version, PPIs, take with water - Caustic esophagitis (strong acids, eg vinegar; strong bases, eg detergents)→ Strong bases are more injurious → liquefactive necrosis, thermal burns→ Retrosternal chest pain, odynophagia, oral burns→ Endoscopy: Lesions classified using Zargar's 4-point grading system→ Treatment: Airway protection/intubation, hemodynamic stabilization, broad spectrum antibiotics, NG tube - Eosinophilic esophagitis (allergic esophagitis)→ Reaction to allergens, foods, or acid reflux→ Individuals who have allergies (seasonal allergies, atopic dermatitis, asthma)→ Symptoms: Failure to thrive, refusal to swallow, regurgitation, vomiting→ Endoscopy: Mucosal fragility, esophageal rings→ Biopsy: Intraepithelial eosinophils, microabscesses near the surface→ Treatment: Prick skin test to identify triggers, PPIs, lfluticasone proprionate spray - Infectious esophagitis→ Candida (oral thrush; white raised plaques), HSV (small punched-out ulcers), CMV (large linear ulcers), HIV (large ulcers)→ Risk factors: Immunocompromised states, diabetes→ Can also cause fevers - Radiation esophagitis
Gastro-ösophageale Refluxkrankheit
Ätiologie: Insuffizienz des unteren Ösophagussphinkters, erniedrigter Ruhetonus, Störungen der Peristaltik (Sklerodermie), erhöhter intraabdomineller Druck (Schwangerschaft, Ileus, Zwerchfellhochstand, Adipositas), Medikamente (Atropin, Kalziumantagonisten, Alkohol), nach Eingriffen (Magenresektion) 1. Spongiose 2. Oberflächliche Koagulationsnekrosen im Plattenepithel 3.. Intraepitheliale Eosinophile und Neutrophile 4. Basalzellhyperplasie und Hyperämie in den Papillen 5. Erosion/Ulzeration
Infektiöse Ösophagitis
Kandidaösophagitis:1. Geflecht (Myzel) aus Hyphen; deutlich erkennbar in Grocott-Versilberung2. Neutrophile Herpes-simplex Ösophagitis:1. Cowdry A Einschüsse2. Neutrophile3. Erosion/Ulzeration Cytomegalievirus Ösophagitis:1. Eulenaugenzellen2. Neutrophile3. Erosion/Ulzeration
Barrett-Ösophagus
Intestinale Metaplasie (Zylinderepithel mit Becherzellen) oberhalb des gastro-ösophagealen Übergangs. Häufigkeit: 10% der Patienten mit symptomatischem gastro-ösophagealem Reflux Prag Klassifikation:- C Kriterium: Zirkumferentielle Ausdehnung - M Kriterium: Maximale Längenausdehnung ab gastro-ösophagealem Übergang Progressionsrisiko für invasives Karzinom- Geringgradige Dysplasie → 0.7% pro Jahr- Hochgradige Dysplasie → 7% pro Jahr Biopsie: - Diagnosebestätigung- Aktivität der Refluxösophagitis- Nachweis und Gradierung einer Epitheldysplasie- Nachweis einer malignen Progression Management and surveillance:- Medical treatment with PPIs- Endoscopy with four-quadrant biopsies at every 2 cm of the suspicious area (salmon colored mucosa)→ If no dysplasia: repeat endoscopy every 3-5 years→ If low-grade dysplasia: Endoscopic therapy of mucosal irregularities→ Alternatively: surveillance every 12 months with biopsies every 1 cm→ If high-grade dysplasia: endoscopic therapy of mucosal irregularities
Magen Histologie
- Foveolae (pits)- Glandulae (glands): Dort, wo sich die Foveolae aufteilen - Hauptzellen (Chief cells): Sezernieren Pepsinogen- Belegzellen (Parietal cells): Produzieren HCl und Intrinsic Factor- Enterochromaffine Zellen (helles Zytoplasma und dunkle runde Kerne)
Gastrointestinaler Stromatumor (GIST)
Mesenchymaler Tumor, der von den Cajal-Zellen des GI-Trakts ausgeht Lokalisation: - Magen (50-60%)- Dünndarm (20-30%)- Selten in Kolon, Rektum (5-10%), Ösophagus, Omentum Klinik:- Oft klein (<2 cm) und asymptomatisch (Zufallsbefund)- >2 cm → Blutung, mechanischer Ileus Subtypen:- Spindelzellig (70%)- Epitheloid (20%)- Gemischt (10%) Marker:- c-KIT (CD117)- DIG1 Therapie: Exzision + Imatinib DD: Andere mesenchymale Tumoren des GI Trakts: Leiomyom/Leiomyosarkom, Lipom, Sarkom, Schwannom
MALT-Lymphom
Mucosa-Associated Lymphoid Tissue (MALT) lymphoma = Extranodal marginal zone lymphoma - Approx. 5% of Non-Hodgkin lymphomas- Peak incidence: 7th and 8th decades Etiology:- Gastric MALTomas: Association with H. pylori infection- Nongastric MALTomas: Association with autoimmune conditions→ Salivary gland MALTomas (Sjögren syndrome)→ Thyroid MALTomas (Hashimoto thyroiditis) Clinical presentation:- Present similarly to peptic ulcer disease and gastritis- Abdominal pain- Melena, hematemesis, potentially anemia- Fatigue, weight loss- Salivary MALToma: parotid enlargement Histopathology and immunohistochemistry:- Thick infiltrates of small to medium-sized lymphoid cells- Granulation tissue, ulcerations- Immunologic phenotyping: markers of B-cell lymphoma (e.g., CD20) Lugano classification (Stage 1-4) Treatment:- First-line: H. pylori eradication therapy→ Should be performed even if patient tests negative→ Eradication of H. pylori is curative in up to 90% of low-malignant gastric MALTomas- If H. pylori eradication therapy fails → radiotherapy or chemotherapy
Crohn's disease
Average age at diagnosis: 15-35 yearsRisk factors: - Nicotine abuse- Familial predisposition: Frameshift mutation in NOD2 gene, HLA-B27 association Symptoms: - Pain in right lower quadrant, diarrhea, malabsorption, clinical features of abscesses (∼50% of cases) and fistulas (∼30% of cases)- Extraintestinal symptoms are more often (except for PSC): Erythema nodosum, uveitis, sacroiliitis, pyoderma gangrenosum Pathology:- Skip lesions (discontinuous inflammation)- Hypertrophic lymph nodes- Transmural inflammation→ Noncaseating granulomas with giant cells (Langhans type)→ Infiltrating neutrophilsMacroscopic findings:- Linear ulcers (snail trails)- Other aphthous hemorrhagic mucosa defects (pinpoint lesions)- Cobblestone sign- Fissures, fistulas- Erythema and transmural inflammation Treatment:- Acute: Corticosteroids- Antidiarrheal agents: Loperamide- 5-Aminosalicylic acid derivatives: Mesalamine, sulfasalazine- Antibiotics: Metronidazole, ciprofloxacin- Immunosuppressants: TNF-α antibodies, azathioprine, methotrexate- Surgical removal
Morbus Crohn
1. Schleimhauterosionen/Ulzera 2. Epitheloidzellige Granuloma ohne Nekrose 3. Transmurale Entzündung mit Fistelbildung 4. Gesamte Wand verdickt Keine Dysplasie des Schleimhautepithels (im Gegensatz zur Colitis ulcerosa).
Ulcerative colitis
Most common form of inflammatory bowel disease, where ulcers form along the inner surface or lumen of the large intestine (colon + rectum).- Risk factors: Family history, young women, Caucasians + Jews Symptoms: Pain in left lower quadrant, (bloody) diarrhea, tenesmus- Uveitis/iritis/episcleritis- Primary sclerosing cholangitis (PSC)- Joints: arthritis, ankylosing spondylitis, sacroiliitis- Skin manifestations: erythema nodosum, pyoderma gangraenosum Gross pathology:- Circumferential and continuous- Ascending inflammation beginning in the rectum - Swelling of the mucosa caused by edema- Small mucosal ulcerations- Loss of mucosal folds- Loss of haustra ('lead pipe' appearance)- Pseudopolyps Histology:- Granulocyte (neutrophils) infiltration: limited to mucosa and submucosa- Crypt abscesses- Mucosal atrophy- Altered crypt architecture→ Branching of crypts→ Irregularities in size and shape- Epithelial dysplasia Treatment:- Anti-inflammatory medications: Sulfasalazine, mesalamine- Immunosuppressors: Corticosteroids, azathioprine, cyclosporin- Biologicals: Infliximab, golimumab, adalimumab- Colectomy
Colitis ulcerosa
1. Lokalisation der Veränderung: Nur Mukosa und Submukosa sind betroffen 2. Schleimhautulzera 3. Kryptenabszesse 4. Pseudopolypen: Inflammatorische Polypen 5. Epitheldysplasien
Peutz-Jeghers syndrome
Rare autosomal dominant condition- Mutation of the STK11 gene (tumor suppressor gene), expressed in a lot of tissues Individuals develop hamartomous polyps throughout their GI tract and melanotic macules in their mouth, lips, genitalia, palms & soles.- Often asymptomatic. If big enough → abdominal pain, constipation, GI bleeding- Increased risk of extraintestinal cancers in GI tract, pancreas, breast, lung, ovaries/uterus, testes. Polyp:- Benign outgrowths- Mostly in the small intestine- May be flat, pedunculated attached by stalk, sessile Diagnosis: - Suspected in individuals with melanotic macules- Colonoscopy for pictures and biopsy → presence of hamartomas- Genetic testing for STK11 gene- Tumor marker screening: CEA for colon cancer, CA19-9 for pancreatic cancer, CA-125 for ovarian cancer
Colonic polyps
Benign:- Hyperplastic polyps→ Most common; generally smaller and predominantly located in rectosigmoid region- Inflammatory polyps→ Due to mucosal erosion in inflammatory bowel disease.- Hamartomous polyps→ Associated with Peutz-Jeghers syndrome and juvenile polyposis. Malignant potential- Adenomatous polyps→ Neoplastic, via chromosomal instability pathway with mutations in APC and KRAS.→ Colonoscopy: pedunculated / sessile→ Histology: tubular / tubulovillous / villous- Serrated polyps→ Characterized by CpG island methylator phenotype. Defect may silence MMR gene (DNA mismatch repair) expression. Mutations lead to microsatellite instability and mutations in BRAF. “Saw-tooth” pattern of crypts on biopsy.
Colorectal carcinoma
Third most common cancer in women and men. Etiology: - Premalignant polyps: adenomatous (APC mutation) and serrated polyps (defects in DNA repair genes)- Risk factors: Elderly, male, IBD, smoking, red meat, alcohol consumption, lack of fiber, obesity, hereditary disorders (familiar adenomatous polyposis, hereditary nonpolyposis)- Ptotective factors: Physical activity, diet rich in fiber and vegetables and lower in meat, long-term use of aspirin and other NSAIDs Stage 0: Carcinoma in situStage 1: Beyond mucosa, no lymph nodesStage 2: Entire wall, no lymph nodesStage 3: Lymph nodesStage 4: Distant organs (if colon, most often liver; if rectal, most often lungs) Symptoms:- Ascending: Exophytic → pain, weight loss; no bowel obstruction; can ulcerate and bleed → anemia- Descending: Infiltrating masses, ring-shaped → lumen narrowing (napkin-ring constriction) → obstruction → colicky abdominal pain, hematochezia Diagnosis: Colonoscopy with biopsy, fecal occult blood testing, ↑ CEA, barium enema (apple-core sign, most often in descending colon) Treatment:- Early → surgical resection- Late → Resection + chemotherapy (FOLFOX = Folinic acid or leucovorin, 5-FU, oxaliplatin; FOLFIRI = folinic acid or leucovorin, 5-FU, irinotecan)
Lynch Syndrom
Etwa 2-5% aller CRC - Junge Patienten (<50 Jahre)- Oft rechtsseitig Pathogenese:- Keimbahnmutation in einem DNA Mismatchrepair-Gen - Praktisch immer BRAF Wildtyp. Assoziierte Karzinome: Endometrium (meist vor Kolon-Karzinom), Magen, Urothel, andere Diagnose:- Goldstandard: Immunhistochemie für MLH1, PMS2, MSH2, MSH6- Microsatellite instability-PCR: 5 Surrogatmarker (Bethesda panel)- Amsterdam II criteria
Esophageal diverticula
Localization:- Upper esophageal diverticulum: Pharyngoesophageal diverticulum→ Most common type: Zenker's diverticulum at Killian's triangle- Middle esophageal diverticulum: diverticulum at the tracheal bifurcation- Lower esophageal diverticulum: epiphrenic diverticulumAlthough a Zenker's diverticulum is considered to be an esophageal diverticulum, it actually arises from the hypopharynx (between thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor muscle)! Histology:- True diverticula: All layers of the esophageal wall protrude.- False diverticula: Increased intraluminal pressure causes only the mucosa and submucosa to bulge through weak points in the muscularis propria. Clinical featuers:- Dysphagia- Regurgitation of undigested food- Aspiration- Coughing after food intake- Retrosternal pressure sensation and pain- Halitosis - Weight loss Diagnostics:- Barium swallow (best confirmatory test) with dynamic continuous fluoroscopy- Endoscopy: to rule out malignancy Treatment: Surgery- Zenker's diverticulum: cricopharyngeal myotomy- Epiphrenic diverticula (symptomatic): esophagomyotomyDiverticula of the middle and distal esophagus (traction diverticula and epiphrenic diverticula) usually do not require treatment!
Portal hypertension
Portal venous pressure of >10 mm Hg (normal value: 3-6 mm Hg). Etiology:- Prehepatic→ Portal vein thrombosis→ Splenic vein thrombosis - Intrahepatic (most common)→ Cirrhosis including fibrous proliferation→ Massive hepatic metastases- Posthepatic→ Budd-Chiari syndrome→ Right-sided heart failure→ Constrictive pericarditis Clinical presentation:- ↑ Blood flow via portosystemic anastomoses - Congestive splenomegaly, followed by signs of hypersplenism- Upper gastrointestinal bleeding from portal hypertensive gastropathy, gastrointestinal ulcers, or diffuse lower gastrointestinal bleeding- Transudative ascites Treatment:- First line medication: nonselective beta-blocker (i.e., propanolol or nadolol)- Transjugular intrahepatic portosystemic shunt (TIPS or TIPSS) Complications: Esophageal variceal hemorrhage, portal hypertensive gastropathy (gastrointestinal ulcers, or diffuse lower gastrointestinal bleeding), ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, cardiac cirrhosis
Esophageal variceal hemorrhage
Esophageal variceal hemorrhage refers to the bleeding of dilated sub-mucosal veins (varices) of the distal esophagus and is a dangerous consequence of portal hypertension. Clinical presentation:- Signs of circulatory insufficiency- Hematemesis- Melena, and/or hematochezia Diagnosis: Clinical- Sudden onset of severe upper GI bleeding in a patient with signs of portal hypertension, typically in combination with liver failure- If bleeding occurs following retching or vomiting, consider a Mallory-Weiss tear as a differential diagnosis. Treatment:- Resuscitation and stabilization- Octreotide for 3-5 days- Vitamin K- IV antibiotics prophylaxis- Endoscopic management: → Erythromycin (a strong prokinetic agent) may be administered before gastroscopy. → Procedures: Endoscopic band ligation, injection sclerotherapy, balloon tamponade
Atrophic gastritis
Condition characterized by chronic inflammation of the gastric mucosa with atrophy, gland loss, and metaplastic changes. Etiology: - Autoimmune metaplastic atrophic gastritis (AMAG)→ Associated with major histocompatibility haplotypes HLA-B8 and HLA-DR3→ Associated with other autoimmune diseases (e.g., autoimmune thyroiditis)→ Autoimmune destruction of the parietal cells→ Autoantibodies against intrinsic factor- Environmental metaplastic atrophic gastritis (EMAG)→ Helicobacter pylori infection (most important risk factor of atrophic gastritis overall)→ Dietary factors (e.g., nitrosamines, alcohol intake) Clinical presentation:- Hematemesis (coffee-ground appearance or bright red in color), possibly melena- Epigastric pain - Nausea, vomiting- Dyspepsia- Additionally in AMAG: iron deficiency anemia (early) and pernicious anemia (late); evidence of other autoimmune diseases Diagnostics:- Esophagogastroduodenoscopy and biopsy- Helicobacter pylori diagnostics Treatment:- General: PPIs, antacids, sucralfate, or H2-receptor blockers - AMAG: Vitamin B12 replacement therapy- EMAG: PPI + clarithromycin + amoxicillin or metronidazole for 7-14 days
Gastric cancer
- Peak incidence: 70 years- High incidence in South Korea and Japan Etiology: - Diet rich in nitrates and/or salts (e.g., dried, preserved food) - Alcohol and nicotine use- Low socioeconomic status- Atrophic gastritis- H. pylori infection: associated with a higher risk of intestinal gastric cancer but not with diffuse gastric cancer- Gastric ulcers- Partial gastrectomy- Adenomatous gastric polyps- Hereditary factors (positive family history, hereditary non‑polyposis colorectal cancer)- Higher incidence in individuals with blood type A Clinical features:- Weight loss, iron deficience anemia- Abdominal pain- Early satiety- Nausea or vomiting- Acute gastric bleeding (hematemesis, melena)- Later: Gastric outlet obstruction, Virchow's nodule, Sister Mary Joseph's nodule, acanthosis nigricans Pathology:- Adenocarcinoma (90% of cases):→ Typically localized, exophytic lesion +/- ulceration→ Arise from glandular cells in the stomach; usually located on the lesser curvature of the stomach- Signet ring cell carcinoma→ Diffuse growth→ Round cells filled with mucin, with a flat nucleus in the cell periphery- Adenosquamous carcinoma- Squamous cell carcinoma- Other: MALT lymphoma, sarcoma, gastrointestinal stromal tumor (GIST), carcinoid Lauren classification of gastric adenocarcinoma:- Intestinal type (∼50% of cases): polypoid, glandular formation; cells look like intestinal cells; expanding (not infiltrative) growth pattern; clear border - Diffuse type (∼40% of cases): infiltrative growth and diffuse spread in the gastric wall; cells secrete mucous; no clear border → larger safety margin- Mixed type (∼10% of cases) Differential diagnosis: Gastric ulcer, GERD, Ménétrier's disease Treatment:- Endoscopic resection- Surgery: Roux-en-Y gastric bypass- Perioperative chemotherapy, sometimes radiotherapy- Trastuzumab is indicated for HER2+ gastric adenocarcinomas
Celiac disease
- Bimodal distribution: At 8-12 months and at 30-40 years- Genetic association to HLA-DQ2 (90-95%) and HLA-DQ8 (5-10%)- Commonly associated with autoimmune diseases Etiology: Consuming gliadin from grains such as wheat, rye, and barley leads to an autoimmune reaction within the small intestinal wall. Clinical presentation:- Chronic or recurring diarrhea: steatorrhea- Flatulence, abdominal bloating, and pain- Nausea/vomiting - Lack of appetite- Malabsorption symptoms: fatigue, weight loss, vitamin deficiency, iron deficiency anemia, osteoporosis- In children: failure to thrive, growth failure, delayed puberty- Dermatitis herpetiformis- Peripheral neuropathies (numbness, burning and tingling of the hands and feet)- Associated conditions: autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune hepatitis, inflammatory bowel disease, rheumatoid arthritis, sarcoidosis, selective IgA deficiency Diagnostics:- Gold standard: IgA (anti‑)tissue transglutaminase antibody (tTG)- IgG deamidated gliadin peptide (DGP)- Anti-endomysial antibody (EMA)- Confirmatory test: Endoscopy with small intestine biopsy→ Villous atrophy→ Crypt hyperplasia→ Intraepithelial lymphocytic infiltration
Carcinoid tumor
Small, slow-growing neuroendocrine tumors. Bimodal distribution: 15–25 years and 65–75 years (but can occur at any age) Location: GI tract, especially in the intestines (55%), bronchopulmonary organ system (30%) Clinical presentation:- Abdominal pain- Carcinoid syndrome: → Diarrhea and abdominal cramps→ Cutaneous flushing→ In severe cases, may be accompanied by tachycardia and fluctuating blood pressure→ Dyspnea, wheezing (asthma-like attacks)→ Palpitations- Carcinoid heart disease:→ Tricuspid insufficiency and/or pulmonary stenosis→ Symptoms of right-sided heart failure- Possible pellagra (niacin deficiency): Triad of dermatitis, diarrhea, and dementia. Diagnostics:- Biochemistry tests: ↑ 5-hydroxyindoleacetic acid (5-HIAA) in 24-hour urine, ↑ serotonin serum levels- Imaging: CT scans of the abdomen and pelvis, somatostatin-receptor scintigraphy, MRI- Biopsy (with histology and immunohistochemistry):→ Numerous small monomorphic cells with salt and pepper chromatin→ Neuroendocrine origin confirmed on immunostaining with synaptophysin, chromogranin A, and neuron-specific enolase (NSE)
Appendicitis
Lifetime risk: ∼8%Peak incidence: 10-19 years of age Etiology: Obstruction of appendiceal lumen by- Lymphoid tissue hyperplasia- Fecalith- Less common: foreign bodies, worm infestations, intestinal infections, tumors (eg, carcinoid tumor) Clinical presentation:- Progressive fever- Anorexia - Nausea, vomiting, diarrhea, and/or constipation- Abdominal pain: → Initially, dull migratory periumbilical pain (due to visceral peritoneum irritation) → After 4-24 hours, sharp RLQ pain (due to parietal peritoneum irritation by a distended and inflamed appendix) with rebound tenderness- Blumberg's sign: rebound tenderness caused upon suddenly ceasing deep palpation of the RLQ- McBurney point tenderness: an area one-third of the distance from the right anterior superior iliac spine to the umbilicus (in the RLQ)- Rovsing's sign: deep palpation of the LLQ causes RLQ referred pain- Psoas sign: RLQ pain with extension of the right leg against resistance (secondary to inflammation of a retrocecal appendix) - Obturator sign: RLQ pain with flexion and internal rotation of the right leg Diagnostics:- ↑ CRP, mild leukocytosis (11,000-15,000 cells/μL) with left shift- Abdominal ultrasound: non-compressible and enlarged appendix (> 6–8 mm)→ Target sign→ Wall thickening→ Edema surrounding the appendix→ In perforation → intra-abdominal free fluid- Abdominal CT scan Differential: Pseudoappendicitis (Yersiniosis), Meckel's diverticulum Therapy:- Bowel rest (keep patient NPO), IV fluid therapy, and observation- Analgesia- Antibiotics with anaerobic and gram negative cover (eg, cefazolin and metronidazole) - Appendectomy Complications: Gangrenous perforation, abscess
Gastroesophageal reflux disease
Chronic condition in which retrograde flow of stomach contents into the esophagus causes irritation to the epithelial lining. Prevalence: ∼15–30% in the US (increases with age) Risk factors/associations:- Lifestyle habits such as smoking and alcohol consumption- Increased intraabdominal pressure: Obesity, pregnancy, ileus, diaphragm dysfunction- Angle of His enlargement (> 60°)- Gastrointestinal malformations and tumors: gastric outlet obstruction, gastric cardiac carcinoma- Scleroderma- Sliding hiatal hernia- Medications: Atropin, calcium antagonists Clinical features:- Retrosternal burning pain (heartburn) that worsens while lying down (e.g., at night) and after eating- Regurgitation- Dysphagia- Chronic non-productive cough - Nausea and vomiting- Halitosis Diagnosis:- If GERD is clinically suspected → Empirical therapy- Upper endoscopy- Esophageal pH monitoring- Esophageal manometry Pathology:- Superficial coagulative necrosis in the non-keratinized squamous epithelium- Thickening of the basal cell layer- Elongation of the papillae in the lamina propria and dilation of the vascular channels at the tip of the papillae (→ hyperemia)- Inflammatory cells (granulocytes, lymphocytes, macrophages)- Transformation of squamous into columnar epithelium → Barrett's metaplasia Treatment:- Lifestyle modifications: Small portions, avoid eating before bedtime, normalize body weight, smoking/alcohol/drug cessation- Treatment of choice: Standard-dose of PPI for at least 8 weeks (once daily therapy)- Fundoplication
Peptic ulcer disease
- >6 million cases annually in the US- Duodenal ulcers are 3 times more common than gastric ulcers Etiology:- Duodenal ulcers: up to 90% are due to H. pylori infection- Gastric ulcers: up to 80% are due to H. pylori infection- Long-term use of NSAIDs plus glucocorticoids: risk increases 10 to 15-fold! - SSRIs- Smoking, alcohol consumption- Age > 65 years- Stress- Zollinger-Ellison syndrome (gastrinoma) Classification:- Gastric ulcer: lesser curvature and the gastric antrum- Duodenal ulcer: duodenal bulb; patients with blood type O have a higher risk; hypertrophy of Brunner glands- Erosive gastritis: acute mucosal inflammation of the stomach that does not extend beyond the muscularis mucosae- Curling ulcer: In patients with severe burns- Cushing ulcer: In patients with brain injury Clinical features:- Dyspepsia: postprandial heaviness, early satiety, and gnawing, aching or burning epigastric pain- Pain relief with antacids- Potential signs of internal bleeding (anemia, hematemesis, melena)- Gastric ulcer: Pain increases shortly after eating → weight loss- Duodenal ulcer: Pain increases 2-5 hours after eating and is relieved with food intake → weight gain Diagnostic approach:≤ 60 years of age without alarm features: Urea breath test for H. pylori> 60 years of age or presence of ≥ 1 alarm features: EGD with biopsies and rapid urease testing for H. pylori Complications:- Bleeding- Perforation- Subhepatic abscess- Gastric outlet obstruction- Fistula formation- Malignant transformation
Whipple disease
Infection with the bacteria Tropheryma whipplei. - Very rare, mainly males 30-60 years of age Clinical features:- Malabsorption syndrome, abdominal pain- Enteropathic arthritis (60% of cases), sacroiliitis (40% of cases)- Fever- Cardiac symptoms (e.g., valve insufficiencies)- Neurological conditions (myoclonia, ataxia, impairment of oculomotor function) Diagnostics:- Small intestine biopsies: detection of PAS-positive macrophages- PCR testing and immunohistochemistry staining- If neurological complaints occur → liquor diagnostics, potentially MRI Treatment:- IV ceftriaxone for 2 weeks- Maintenance treatment with oral trimethoprim-sulfamethoxazole for 1 year
Stomach histology
Cardia:- Epithelium: transition of mucosal epithelium from squamous to columnar epithelium (intestinal) Fundus and body:- Epithelium: rugae with shallow pits and deep glands- Contains mucus cells, gastric chief cells, parietal cells, and enteroendocrine cells Antrum:- Mucosa: rugae with shallow pits and deep glands- Contains mucus cells, G cells (secrete gastrin), and D cells (secrete somatostatin) Pylorus:- Mucosa: rugae with deep pits and shallow glands- Contains the pyloric sphincter of circular smooth muscle
Diverticular disease
- Common in Western countries and industrialized societies (∼50% of people > 60 years affected) Etiology:- Genetic factors- Diet (low-fiber, rich in fat and red meat)- Obesity, low physical activity- Cigarette consumption Classification: Hinchey Clinical features:- Diverticulosis→ Mostly asymptomatic→ Most common cause of lower GI bleeding in adults→ Can present with abdominal pain in patients with chronic constipation- Diverticulitis→ Low-grade fever→ Sigmoid colon most commonly affected → left lower quadrant pain→ Possibly tender, palpable mass (pericolonic inflammation)→ Change in bowel habits (∼50% constipation, 25-35% diarrhea)→ Nausea and vomiting; caused by bowel obstruction or ileus→ Acute abdomen → indicates possible perforation and peritonitis Treatment:- Acute uncomplicated diverticulitis: Broad-spectrum oral antibiotics for 7–10 days (Ciprofloxacin plus metronidazole)- Acute complicated diverticulitis: Broad-spectrum IV antibiotics (Piperacillin/tazobactam)- Emergency surgery: in case of peritonitis, sepsis or intestinal obstruction Complications:- Bleeding- Abscess- Perforation- Fistulas- Intestinal obstruction
