Viêm tụy mạn Chronic pancreatitis

Chronic pancreatitis I/ Summary Chronic pancreatitis is caused by progressive inflammation and irreversible damage to the structure and function (exocrine and endocrine) of the pancreas Alcohol abuse is the most common known etiological factor, followed by pancreatic ductal obstruction Idiopathic pancreatitis accounts for up to 30% of cases Patients may be asymptomatic or present with abdominal pain and features of pancreatic enzyme insufficiency (e.g., steatorrhea, weight loss, impaired glucose tolerance) Diagnosis is confirmed on imaging, which demonstrates pancreatic calcifications, ductal strictures, and ductal dilations Pancreatic function tests (e.g., fecal elastase-1 measurement, 72-hour fecal fat estimation) assess the degree of enzyme deficiency Symptomatic patients are successfully managed with oral pancreatic enzyme replacements and analgesics Patients with chronic pain require additional interventions (e.g., celiac ganglion block, partial/complete pancreatic resection) II/ Etiology  Alcohol abuse (60–70% of cases, esp men) ,  Pancreatic ductal obstruction (< 10%): strictures (e.g., due to trauma, stones)  Tobacco use  Idiopathic pancreatitis (20–30%)  Hereditary pancreatitis (∼1%): autosomal dominant inheritance (PRSS1 gene mutation), age of onset < 20 years  Autoimmune pancreatitis  Systemic disease  Severe hypertriglyceridemia (levels > 1000mg/dl)  Primary hyperparathyroidism (hypercalcemia)  Cystic fibrosis: ∼ 2% of cystic fibrosis patients develop chronic pancreatitis  Tropical pancreatitis: most common cause in the Tropics (esp Southern India); young age at onset III/ Pathophysiology  Autodigestion and inflammation: damage to pancreatic acinar cells (e.g., alcohol), outflow obstruction of pancreatic enzymes or premature activation of trypsinogen to trypsin → intrapancreatic activation of digestive enzymes (e.g., amylase and lipase) → autodigestion of pancreatic tissue → inflammatory reaction  Fibrosis: exposure to toxins and/or inflammatory mediators (e.g., alcohol, cytokines) → activation of pancreatic stellate cells (which play a key role in the formation of pancreatic fibrosis)  Pancreatic insufficiency (due to tissue atrophy and fibrosis)  Exocrine insufficiency → deficiency of lipase, amylase, and protease → maldigestion, steatorrhea, malabsorption  Endocrine insufficiency → destruction of β-cells → pancreatic diabetes VI/ Clinical features  Epigastric abdominal pain (main symptom)  Pain radiates to the back, is relieved on bending forwards and exacerbated after eating  Pain is initially episodic and becomes persistent as the disease progresses  Often associated with nausea and vomiting  Features of pancreatic insufficiency  Late manifestation (after 90% of the pancreatic parenchyma is destroyed)  Steatorrhea (exocrine hormone deficiency)  Cramping abdominal pain, bloating, diarrhea, weight loss  May cause fat-soluble vitamin deficiencies (A, D, E, and K)  Malabsorption and weight loss  Pancreatic diabetes (endocrine hormone deficiency) !!! In the later stages of chronic pancreatitis, patients may not experience any pain! V/ Diagnostics Imaging  Abdominal CT (plain and contrast-enhanced): best initial imaging modality to screen for CP  Findings: pancreatic atrophy, pancreatic ductal dilations; pancreatic ductal calcifications on plain CT (more sensitive than x-ray); “chain of lakes” appearance  Can simultaneously rule out a pancreatic carcinoma or a gastrointestinal malignancy as a possible cause of epigastric pain and weight loss  MRCP: indicated when CT findings are equivocal but clinical suspicion of CP is high  Findings: ductal strictures and dilations, pancreatic calcifications  Abdominal x-ray: visible pancreatic calcifications (highly specific, but only seen in ∼ 30% of cases)  Ultrasound  Abdominal ultrasound: indistinct margins and enlargement; pancreatic calcifications; ductal strictures, dilation or stones  Endoscopic ultrasound: parenchymal lobularity and hyperechoic foci; ductal dilation and calcification  ERCP: detection of early pathologies and simultaneous treatment possible (e.g., duct dilation, stent insertion)  Ductal stones, seen as filling defects  “Chain of lakes” or “string of pearls” appearance (characteristic feature)  Irregularity, dilation of the main pancreatic duct Laboratory tests  Serum pancreatic enzyme levels: lipase (specific) and amylase (non-specific)  Pancreatic function tests  Indirect tests:  Fecal elastase-1 (FE-1) activity: confirms that steatorrhea is due to pancreatic lipase insufficiency  Elastase-1 level < 200 μg/g → pancreatic exocrine insufficiency  Elastase-1 level < 100 μg/g → severe pancreatic exocrine insufficiency  72-hour quantitative fecal fat estimation: Fecal fat > g per day is diagnostic of steatorrhea  Direct tests (e.g., cholecystokinin test, secretin test, cholecystokinin-secretin pancreatic function test) Genetic testing  Indication: family history of chronic pancreatitis; young patients with idiopathic pancreatitis  PRSS-1 mutations: diagnostic of hereditary pancreatitis  CFTR gene: 40% of patients with idiopathic chronic pancreatitis have a CFTR gene mutation VI/ Treatment General measures  Abstinence from alcohol and nicotine  Small, regular meals (rich in carbohydrates, low in fat), supplementation with medium-chain triglycerides (MCT)  Pancreatic enzyme replacement (with meals)  Parenteral administration of fat-soluble vitamins (A, D, E, K) if necessary  Endocrine insufficiency: Insulin administration  For management of acute attacks see “Treatment” in acute pancreatitis Pain management  Analgesics: NSAIDs, opioids for severe pain (e.g., long-acting fentanyl/morphine), low dose tricyclic antidepressants (e.g., amitriptyline)  Intractable pain  Celiac ganglion block (offers temporary relief)  Endoscopic papillotomy + ductal dilation and stent placement + removal of stones, if present  Extracorporeal shock wave lithotripsy (ESWL): for intraductal stones Surgery  Indication: if pancreatic cancer is suspected or in those with intractable pain  Procedures  Pancreaticojejunostomy: if the main pancreatic duct is dilated (> mm)  Resection of the affected part of the pancreas (distal pancreatectomy, Whipple's procedure)  Thoracoscopic bilateral splanchnicectomy VII/ Complications Pancreatic pseudocysts  Definition: encapsulated collection of pancreatic fluid which develops weeks after an acute attack of pancreatitis; can occur in both acute and chronic pancreatitis  Pathophysiology: pancreatic secretions leak from damaged ducts → inflammatory reaction of surrounding tissue → encapsulation of secretions by granulation tissue  Clinical features  Often asymptomatic  Painless abdominal mass  Pressure effects  Gastric outlet obstruction (early satiety, non-bilious vomiting, abdominal pain)  Obstruction of the distal duodenum (bilious vomiting)  Results in steatorrhea  Bile duct obstruction with jaundice  Diagnostics: abdominal ultrasound/CT/MRI → extrapancreatic fluid collection within well-defined wall/capsule, no solid cyst components detectable  Treatment : Surgical/endoscopic cystogastrostomy/cystoduodenostomy/cystojejunostomy ; ultrasound/CTguided percutaneous drainage  Complications  Infection → fever, abdominal pain, sepsis  Rupture → pancreatic ascites/pancreaticopleural fistula  Erosion into an abdominal vessel with hemorrhage into the cyst → sudden abdominal pain, signs of hemorrhagic shock Splenic vein thrombosis  Can occur in 10% of patients with chronic pancreatitis  Pathophysiology: inflammation of the splenic vein → thrombus formation → left-sided portal hypertension → gastric varices  Clinical features: can present with upper GI bleeding, ascites, and splenomegaly  Diagnosis: ultrasound with doppler, CT/MR angiography  Treatment  Acute: anticoagulation and/or thrombectomy  Chronic and symptomatic: splenectomy Pancreatic ascites  Pathophysiology: Ductal disruption (due to an acute attack of pancreatitis; pancreatic surgery/trauma) or a pseudocyst leak/rupture → pancreatic ascites  Clinical features  Abdominal distension; variable abdominal pain; dyspnea ; peripheral edema  Free fluid in the peritoneal cavity  Diagnosis  Ascitic fluid analysis: Exudate with high amylase levels (> 1000 IU/L)  ERCP: Demonstrates the site(s) of leak  CECT and MRCP can also demonstrate ascites and the site of leak; ERCP is preferred since treatment can be performed in the same sitting  Treatment  Conservative manangement: Indicated in all patients; ∼ 30% will require no further treatment  Nil per oral, IV fluids, parenteral nutrition  Somatostatin analogues (octreotide)  Repeated ascitic taps  Stenting of the pancreatic duct: If ERCP demonstrates ductal disruption  Surgery: Indicated in patients with no improvement on conservative management for weeks (See Pancreatic and hepatic surgery)  Pancreatic resection  Surgery for pancreatic pseudocyst  Lateral pancreaticojejunostomy Further complications  Pancreatic abscess  Portal vein thrombosis  Pancreatic diabetes  Pancreatic cancer (especially in patients with hereditary pancreatitis)  We list the most important complications The selection is not exhaustive QUESTION Q1 A 49-year-old man comes to the emergency department because of recurrent abdominal pain for week The pain is worse after eating and he has vomited twice during this period He was hospitalized twice for acute pancreatitis during the past year; the latest being months ago There is no family history of serious illness His only medication is a vitamin supplement He has a history of drinking five beers a day for several years but quit month ago His temperature is 37.1°C (98.8°F), pulse is 98/min and blood pressure 110/70 mm Hg He appears uncomfortable Examination shows epigastric tenderness to palpation; there is no guarding or rebound A CT scan of the abdomen shows a 6-cm low attenuation oval collection with a well-defined wall contiguous with the body of the pancreas Which of the following is the most appropriate next step in management? A Magnetic resonance cholangiopancreatography B CT-guided percutaneous drainage C Middle segment pancreatectomy D Distal pancreatectomy E Laparoscopic surgical drainage F Observation and reimaging in weeks Q2 A 12-year-old girl is brought to the physician because of a 2-hour history of severe epigastric pain, nausea, and vomiting Her father has a history of similar episodes of abdominal pain and developed diabetes mellitus at the age of 30 years Abdominal examination shows guarding and rigidity Ultrasonography of the abdomen shows diffuse enlargement of the pancreas; no gallstones are visualized Which of the following is the most likely underlying cause of this patient's condition? A Defective bilirubin glucuronidation B Elevated serum amylase levels C Increased β-glucuronidase activity D Premature activation of trypsinogen E Defective elastase inhibitor F Impaired cellular copper transport Q3 A 55-year-old woman is brought to the emergency department because of worsening upper abdominal pain for hours She reports that the pain radiates to the back and is associated with nausea She has hypertension and hyperlipidemia, for which she takes enalapril, furosemide, and simvastatin Her temperature is 37.5°C (99.5 °F), blood pressure is 84/58 mm Hg, and pulse is 115/min The lungs are clear to auscultation Examination shows abdominal distention with epigastric tenderness and guarding Bowel sounds are decreased Extremities are warm Laboratory studies show: Hematocrit 48% Leukocyte count 13,800/mm3 Platelet count 175,000/mm3 Serum: Calcium 8.0 mg/dL Urea nitrogen 32 mg/dL Amylase 250 U/L An ECG shows sinus tachycardia Which of the following is the most likely underlying cause of this patient's vital sign abnormalities? A Decreased sympathetic tone B Hemorrhagic fluid loss C Decreased albumin concentration D Abnormal coagulation and fibrinolysis E Decreased cardiac output F Increased excretion of water G Pseudocyst formation H Capillary leakage Q4 A 57-year-old man comes to the physician because of a 3-week history of abdominal bloating and increased frequency of stools He describes the stools as bulky, foul-smelling, and difficult to flush He also has a 4-month history of recurrent dull upper abdominal pain that usually lasts for a few days, worsens after meals, and is not relieved with antacids He has had a 10-kg (22-lb) weight loss in the past months He has no personal or family history of serious illness He has smoked pack of cigarettes daily for 37 years He has a 12-year history of drinking to beers daily He is 160 cm (5 ft in) tall and weighs 52 kg (115 lb); BMI is 20 kg/m2 His vital signs are within normal limits Abdominal examination shows mild epigastric tenderness without rebound or guarding Bowel sounds are normal The remainder of the examination shows no abnormalities Which of the following is the most appropriate next step in diagnosis? A Abdominal CT scan B Measurement of serum cancer antigen 19-9 C Endoscopic ultrasonography D Abdominal ultrasound E Upper gastrointestinal endoscopy F Endoscopic retrograde cholangiopancreatography G Abdominal x-ray Q5 A 72-year-old man is brought to the physician by his son because of gradually progressive yellow discoloration of his skin and generalized pruritus for the past weeks During this period, his appetite has decreased and he has had a 6.3-kg (14-lb) weight loss He reports that his stool appears pale and his urine is very dark Three years ago, he had an episode of acute upper abdominal pain that was treated with IV fluids, NSAIDs, and dietary modification He has stopped drinking alcohol since then; he used to drink 1–2 beers daily for 40 years He has smoked a pack of cigarettes daily for the past 50 years His vital signs are within normal limits Physical examination shows yellowing of the conjunctivae and skin The abdomen is soft and nontender; a soft, cystic mass is palpated in the right upper quadrant Serum studies show: Bilirubin: Total 5.6 mg/dL Direct 4.8 mg/dL Alkaline phosphatase 192 U/L AST 32 U/L ALT 34 U/L Abdominal ultrasonography shows an anechoic cystic mass in the subhepatic region and dilation of the intrahepatic and extrahepatic bile ducts Which of the following is the most likely diagnosis? A Pancreatic adenocarcinoma B Acute cholangitis C Choledocholithiasis D Alcoholic hepatitis E Cholecystitis F Budd-Chiari syndrome G Pancreatic pseudocyst Q6 A 42-year-old man comes to the physician because of severe epigastric pain for a week The pain is constant and he describes it as out of 10 in intensity The pain radiates to his back and is worse after meals He has had several episodes of nausea and vomiting during this period He has taken ibuprofen for multiple similar episodes of pain during the past months He also has had a 5.4-kg (12-lb) weight loss over the past months He has a 12-year history of drinking to pints of rum daily He has been hospitalized three times for severe abdominal pain in the past years He appears ill His temperature is 37°C (98.6°F), pulse is 87/min, and blood pressure is 110/70 mm Hg There is severe epigastric tenderness to palpation Bowel sounds are normal Cardiopulmonary examination shows no abnormalities Laboratory studies show: Hemoglobin 13.6 g/dL Leukocyte count 7800/mm3 Serum Glucose 106 mg/dL Creatinine 1.1 mg/dL Amylase 150 U/L A CT of the abdomen is shown Which of the following is the most appropriate long-term management for this patient? A Gluten-free diet B Whipple procedure C Opioid therapy D Endoscopic stent placement E Pancreatic enzyme therapy F High-fiber diet G Celiac ganglion block Q7 A 49-year-old man comes to the physician because of a 1-week history of diarrhea and abdominal bloating His stools are bulky, foul-smelling, and difficult to flush Over the past months, he has had recurrent dull epigastric pain that is triggered by meals and lasts for a few days He drinks to beers daily Abdominal examination shows mild epigastric tenderness with no rebound or guarding A CT scan of the abdomen is shown The structure indicated by the arrows is most likely lined by which of the following? A Simple ductal epithelium B Calcified ductal cells C Granulation tissue D Pyogenic membrane E Columnar mucinous epithelium Q8 A 47-year-old woman with chronic epigastric pain comes to the physician because of a 1-month history of intermittent, loose, foulsmelling stools She has also had a 6-kg (13-lb) weight loss She has consumed 9–10 alcoholic beverages daily for the past 25 years Seven years ago, she traveled to Mexico on vacation; she has not been outside the large metropolitan area in which she resides since then She appears malnourished The stool is pale and loose; fecal fat content is elevated An immunoglobulin A serum anti-tissue transglutaminase antibody assay is negative Further evaluation is most likely to show which of the following A Inflammation of subcutaneous fat B Trophozoites on stool microscopy C Pancreatic calcifications D Villous atrophy of duodenal mucosa E Positive lactulose breath test Q9 A previously healthy 20-year-old woman comes to the physician because of recurrent abdominal cramps, bloating, and diarrhea for months She describes her stools as greasy, foul-smelling, and difficult to flush During this time she has had a 6-kg (13.2-lb) weight loss She has no personal or family history of serious illness Physical examination shows pallor and cheilitis Laboratory studies show a hemoglobin concentration of 11 g/dL Serum concentrations of electrolytes, urea nitrogen, and creatinine are within the reference range Test of the stool for occult blood is negative and stool microscopy reveals no pathogens and no leukocytes Analysis of a 24-hour stool sample shows 12 g of fat The patient is asked to consume 25 g of d-xylose Five hours later, its concentration is measured in urine at g (N = > g/5 h) The test is repeated after a two-week course of rifaximin, but the urinary concentration of d-xylose remains the same Which of the following is the most likely diagnosis? A Autoimmune-mediated inflammation of the colon B Lactose intolerance C Exocrine pancreatic insufficiency D Tropheryma whipplei infection E Bacterial overgrowth in the small intestine F Hypersensitivity to gliadin Q10 A 37-year-old woman comes to the physician because of a 6-month history of weight loss, bloating, and diarrhea She does not smoke or drink alcohol Her vital signs are within normal limits She is 173 cm (5 ft in) tall and weighs 54 kg (120 lb); BMI is 18 kg/m2 Physical examination shows bilateral white spots on the temporal half of the conjunctiva, dry skin, and a hard neck mass in the anterior midline that does not move with swallowing Urinalysis after a D-xylose meal shows an increase in renal D-xylose excretion Which of the following is most likely to have prevented this patient's weight loss? A Gluten-free diet B Pancreatic enzyme replacement C Tetracycline therapy D Mesalamine therapy E Lactose-free diet Q11 A 58-year-old man comes to the physician because of a 4-day history of abdominal pain and vomiting Initially, the vomitus was food that he had recently eaten, but it is now bilious He has had similar complaints several times in the past years He has smoked pack of cigarettes daily for the past 25 years and drinks 24 oz of alcohol daily He is 160 cm (5 ft in) tall and weighs 48 kg (105 lb); BMI is 19 kg/m2 His vital signs are within normal limits Physical examination shows an epigastric mass The remainder of the examination shows no abnormalities Which of the following is the most likely diagnosis? A Chronic cholecystitis B Retroperitoneal fibrosis C Hypertrophic pyloric stenosis D Pancreatic pseudocyst E Gastric adenocarcinoma ANSWER 10 11 B D H A A E C C F B D ... history of chronic pancreatitis; young patients with idiopathic pancreatitis  PRSS-1 mutations: diagnostic of hereditary pancreatitis  CFTR gene: 40% of patients with idiopathic chronic pancreatitis. .. collection of pancreatic fluid which develops weeks after an acute attack of pancreatitis; can occur in both acute and chronic pancreatitis  Pathophysiology: pancreatic secretions leak from damaged... pain, signs of hemorrhagic shock Splenic vein thrombosis  Can occur in 10% of patients with chronic pancreatitis  Pathophysiology: inflammation of the splenic vein → thrombus formation → left-sided