Χρόνια Παγκρεατίτιδα και Λιπάση

Chronic Pancreatitis

• A soft, elongated, flattened gland, measuring 12-20 cm in length.
• Located in the epigastric and left hypochondriac regions of the abdominal cavity.

Functions of the Pancreas

• Endocrine Functions:
  • Islet of Langerhans
  • Alpha cells: glucagon (20%)
  • Beta cells: insulin (75%)
  • Delta cells: somatostatin
• Exocrine Functions:
  • Pancreatic juice
  • Amylase
  • Lipase
  • Trypsin
  • Chymotrypsin
  • Carboxypeptidase

Protein Digestion

• Trypsinogen and Chymotrypsinogen are inactive enzyme precursors.
• Activated by enterokinase to trypsin and chymotrypsin, which convert polypeptides to tripeptides and dipeptides.

Carbohydrate Digestion

• Amylase converts polysaccharides to disaccharides.

Fat Digestion

• Lipase converts fats to fatty acids.

Chronic Pancreatitis - Definition

• Historically defined as an irreversible inflammatory condition of the pancreas, leading to exocrine and endocrine dysfunction.
• Recently defined as a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress.

Epidemiology of Chronic Pancreatitis

• Annual incidence estimates range from 3-9 cases per 100,000 population in retrospective studies.
• One prospective study, focusing on alcoholic CP, reported an annual incidence of 8.2 cases per 100,000 and an overall prevalence of 35.5 cases per 100,000.
• A Japanese nationwide survey revealed a 3.5:1 male-to-female ratio.
• 10-year survival is approximately 70%, and 20-year survival is about 45%.

Socioeconomic Effects of Chronic Pancreatitis

• One-third of chronic pancreatitis patients are unable to pursue their professional careers.
• The rate of people losing gainful employment due to prolonged illness or continued alcohol consumption, and the rate of disability, reaches 40%.
• Continued alcohol consumption, smoking, and the presence of cirrhosis have adverse effects on the prognosis of chronic pancreatitis.

Etiology of Chronic Pancreatitis (TIGAR-O Checklist)

• Includes factors like toxic and metabolic (e.g., alcohol, smoking, hypercalcemia), idiopathic, genetic (e.g., CFTR gene mutations), autoimmune, recurrent and severe acute pancreatitis, and obstructive causes.

Alcohol as a Risk Factor

• The risk for developing chronic pancreatitis increases with consumption of more than 80g of alcohol per day for 6-12 years.
• The type of alcohol consumed does not influence the increased risk.
• Patients with chronic pancreatitis or cirrhosis do not differ significantly in terms of alcohol consumption.
• On average, 18 ± 11 years elapse between the start of excessive alcohol consumption and the development of pancreatitis.

Clinical Manifestations of Chronic Pancreatitis

• Recurrent episodes of severe and uncontrollable upper abdominal pain.
• Diarrhea/steatorrhea (loss of exocrine function).
• Diabetes mellitus (loss of endocrine function).

Abdominal Pain (Characteristics)

• No distinct pain pattern.
• Typically felt in the epigastrium, radiating to the back.
• Associated nausea and vomiting.
• Pain may worsen after meals and be nocturnal.
• Relieved by sitting forward or assuming a knee-chest position.

Exocrine Insufficiency (Steatorrhea)

• Occurs when pancreatic lipase secretion is reduced to less than 10%.
• Feature of advanced chronic pancreatitis.
• Characterized by maldigestion of fats, proteins, and carbohydrates.
• Results in bulky, foul-smelling stools.

Endocrine Insufficiency (Diabetes Mellitus)

• Half of patients with chronic pancreatitis who develop diabetes mellitus require insulin.
• Diabetes complications are equally common in patients with CP as in those with type 1 diabetes having similar disease duration.
• DM development in CP is most likely related to disease duration.

Diagnosis of Chronic Pancreatitis

• Functional tests
• Imaging

Laboratory Studies

• Serum amylase and lipase may be elevated, or frequently normal.
• When fibrosis occurs, enzymes generally do not increase.
• CBC, electrolytes, and LFTs are usually normal.
• TB and ALP may be elevated, indicating possible bile duct compression.
• Autoimmune pancreatitis: Elevated ESR, IgG4, RF, ANA, anti-smooth muscle antibody.
• Steatorrhea: 72-hour fecal fat determination (excretion >7g fat per day).
• Fecal elastase is a more sensitive and specific test.

Functional Tests

• Hormonal tests of pancreatic function (CCK stimulation test, secretin stimulation test)- evaluate acinar and ductal cell functions, respectively.
• Non-hormonal tests of pancreatic function (fecal elastase-1, 13C-mixed triglyceride test) - Assess pancreatic function via non-invasive means.

Imaging of Chronic Pancreatitis

• Test of choice previously: ERCP
• Test of choice now: CECT
• CT scan demonstrates 85-100% specificity for chronic pancreatitis and may show findings like dilated pancreatic duct, parenchymal atrophy, and pancreatic calcifications.
• MRI, MRCP are alternative, reliable techniques, especially for intraductal strictures and pancreatic duct disruption.
• ERCP historically considered the "gold standard"; indicated when CT and MRCP fail or are contraindicated.
• EUS has emerged as the most accurate technique to diagnose chronic pancreatitis in its early stages.
• Rosemont Criteria uses EUS findings to classify the extent of involvement of pancreatic tissue.

Treatment of Chronic Pancreatitis

• Medical, endoscopic, surgical intervention.

Pain Management of Chronic Pancreatitis

• Pain management in chronic pancreatitis presents a challenge.
• A stepwise approach to pain using general recommendations, pancreatic enzyme supplementation, analgesic use, and invasive/surgical therapies is used.
• General recommendations: Cessation of alcohol and smoking, small low-fat meals, hydration.
• Medical management: Non-narcotic analgesics (e.g., acetaminophen) as first-line therapy, consider lower potency opioid agents if needed. Gradually increase dosage as appropriate.
• Other medical therapies: Acid suppression may reduce enzyme inactivation.

Pancreatic Enzyme Supplements

• Used to manage pancreatitis.
• Suppresses feedback loops in the duodenum that control CCK release.
• A reduced intraduodenal free enzyme activity may increase CCK-releasing factors, thereby increasing in intraduodenal enzyme activity.
• Beneficial for patients without large duct involvement, without steatorrhea, or idiopathic chronic pancreatitis.

Other Medical Therapies

• Acid suppression: H2 receptor blockers or proton pump inhibitors reduce inactivation of enzymes caused by gastric acid.
• Octreotide: Not enough data to determine efficacy.
• Antioxidant therapy: Vitamins C, E, methionine, and selenium may help reduce oxidative stress and inflammation; more data are required.
• Celiac nerve block: Can be used as part of pain relief (injections of a local anesthetic).
• Endoscopic stenting of the pancreatic duct or pancreatic sphincterotomy.
• Extracorporeal shock wave lithotripsy (ESWL): Used for pancreatic duct stones with the objective of pain relief and improved endoscopic results.
• Surgery

Complications of Chronic Pancreatitis

• Pseudocyst: Collection of fluid and debris within the pancreas.
• Pancreatic abscess: Cavity of pus within the pancreas.
• Diabetes: Caused by damage to insulin-producing cells.
• Pancreatic ascites: Persistent leakage of pancreatic juice from a pseudocyst.
• Pancreatic fistula: Occurs after operative or percutaneous drainage of a pseudocyst.
• Malnutrition: Due to lack of absorption.
• Splenic vein thrombosis: Result of peripancreatic inflammation.

Surgical Procedures for Chronic Pancreatitis

• Decompression procedures (like lateral pancreaticojejunostomy) are used.
• Ressection procedures (Whipple procedure, distal pancreatectomy, total pancreatectomy with islet autotransplantation) are indicated when less invasive treatments fail; choice depends on the disease's location and extent.
• Denervation procedures (trans-hiatal splanchnicectomy) may reduce pain.

Pancreatic Cancer

• Carcinoma of the exocrine pancreas accounts for 90% of pancreatic tumors.
• A biologically aggressive tumor from the onset.
• Only 20% are operable for cure.
• Survival is approximately 10-15% at 12 months post-diagnosis.

Risk Factors for Pancreatic Cancer

• Cigarette smoking.
• Obesity.
• Chronic calcific pancreatitis.
• Hereditary pancreatitis.
• Inherited cancer syndromes (e.g., hereditary breast/ovarian cancer syndrome, FAMMM, Peutz-Jeghers syndrome, Lynch syndrome, ataxia-telangiectasia, Li-Fraumeni syndrome).
• Family history of pancreatic cancer in multiple family members, first-degree relatives, and/or younger relatives (<50 years old).

Clinical Presentation of Pancreatic Cancer

• Often called "silent disease"; symptoms don't appear in early stages, making diagnosis challenging.
• When symptoms appear, these may include:
  • Weight loss
  • Anorexia
  • Nausea and vomiting
  • Abdominal pain
  • Obstructive jaundice (painless jaundice; head lesions)
  • New onset or worsening of pre-existing diabetes.

Investigations for Pancreatic Cancer

• Bloods:
  • ESR usually raised.
  • LFTs may be normal.
  • Tumor marker CA 19-9 may be elevated and/or 70-90% specificity, sometimes seen in benign diseases.
• Imaging:
  • CT scan with IV contrast to identify pancreatic mass.
  • Abdominal ultrasound is the initial test to look for biliary obstruction.
  • MRI and MRCP are useful for staging.
  • EUS is useful for real-time high-resolution imaging and tissue sampling.
  • ERCP is used for therapeutic interventions, including biliary stents
• CT Scan: Main modality for diagnosing pancreatic cancer.
• MRI: Used when CT is inconclusive. Includes MRCP to evaluate the biliary ducts.
• Biopsy: Indicated for differential diagnosis and before initiating chemotherapy; not routinely performed if surgical resection is planned; EUS-guided fine-needle biopsy is preferred.

Pathology of Pancreatic Cancer

• Most cases (80%) are pancreatic ductal adenocarcinoma (PDAC).
• Other types include adenocarcinomas, undifferentiated carcinomas, and acinar-cell carcinomas.

Staging of Pancreatic Cancer

• The TNM (Tumor, Node, Metastasis) system is used to stage pancreatic cancer.
• Resection is potentially curative in only approximately 20% of cases; treatment options for unresectable cancers vary and include measures to address the most pressing symptoms.

Treatment of Pancreatic Cancer

• Resection: Whipple procedure is the standard approach if resectable. Biliary bypass + gastric bypass is an option for unresectable cases.
• Resectability criteria: Based on the degree of contact between the tumor and peripancreatic vessels. Patients are classified as resectable, borderline resectable, locally advanced, or metastatic.

Cholangiocarcinoma

• Cancers arising from the bile duct epithelium.
• The intrahepatic, peri-hilar, and distal (extrahepatic) bile ducts are potential sites.
• Tumors involving the proper hepatic duct bifurcation are termed Klatskin tumors or hilar cholangiocarcinomas.
• Bismuth-Corlette classification categorizes CCA based on location and extent.
• Incidence is geographically variable; highest in northeastern Thailand.

Risk Factors for Cholangiocarcinoma

• Unknown in most cases.
• Potential factors include primary sclerosing cholangitis, liver fluke infestation, Caroli disease, bile duct cysts, chronic intraductal stones, chronic liver cirrhosis, chronic viral hepatitis, surgical biliary-enteric drainage procedures, toxins, obesity, and metabolic syndrome.

Clinical Presentation of Cholangiocarcinoma

• Typically a painless obstructive jaundice.
• Additional symptoms include pruritus (itching), abdominal pain, weight loss, and fever.
• Hepatomegaly and right upper quadrant mass may be present in more advanced cases.

Diagnosis of Cholangiocarcinoma

• Laboratory Studies:
  • Elevated TBIL (total bilirubin) greater than 10 mg/dL, along with DBIL and ALK phosphatase are common.
  • Elevated AST, ALT, and GGT are sometimes present.
  • Carcinoembryonic antigen (CEA) and CA 19-9 are not specific but may be helpful
• Imaging:
  • Contrast CT or MRI, to visualize any arterial or venous enhancement.
  • MRCP or cholangiography to evaluate the biliary ducts.
  • ERCP or PTC may also be useful.
• CT Scan: Is useful for detecting intra-hepatic tumors, level of biliary obstruction, and liver atrophy. Klatskin tumors (bile duct bifurcation) manifest as ductal dilation and thickened walls in both lobes, along with a contracted gall bladder and non-union of the right and left hepatic duct.
• MRCP: Non-invasive technique; useful for evaluating duct systems; does not require contrast agents; T1/T2 imaging demonstrates hypo/hyper intense lesions, respectively; findings such as central hypointensity suggest fibrosis.

Treatment of Cholangiocarcinoma

• Surgical Treatment:
  • Intrahepatic CCA: Hepatic segmentectomy or lobectomy
  • Distal extrahepatic CCA: Pancreatoduodenectomy
  • Hilar CCA: Biliary duct resection +/- hepatic lobectomy
• Palliation: Aim to reduce pain and jaundice. ERCP or percutaneous stenting as appropriate.

Ampullary Carcinoma

• Tumors arising within the ampullary complex, distal to the common bile duct and pancreatic duct confluence.
• Neoplastic transformation frequently develops near the ampulla.
• Common in patients aged 60 to 70+.
• Presenting symptoms often include obstructive jaundice, diarrhea (fat malabsorption), weight loss, and fatigue.
• Occult GI blood loss and associated microcytic anemia are observed in about one-third of cases.
• Large lesions present with gastric outlet obstruction and nausea/vomiting.

Diagnosis and Staging of Ampullary Carcinoma

• Liver biochemical tests: No determination of ampullary carcinoma; possible elevation in liver enzymes.
• Aminotransferases: May increase.
• PT: May be elevated due to impairment in fat-soluble vitamin absorption.
• CA 19-9 and CEA: Not specific to ampullary cancer.
• Abdominal ultrasound: Initial test, helpful for evaluating obstructive jaundice.
• Helical CT: Helps visualize the pancreas and surrounding structures; not always sufficient for diagnosing the tumor.
• ERCP: Most valuable endoscopic technique for identifying the tumor, performing biopsies, and providing decompression.
• EUS: Generally not needed.

Prognosis of Ampullary Carcinoma

• Prognosis depends on extent of local invasion and lymphatic spread, not the presence of metastases.
• The outcome of resected ampullary cancer is determined by the extent of local invasion, status of surgical margins, and presence/absence of nodal metastases.

Treatment of Ampullary Carcinoma

• Potentially curative treatment is surgical resection.
• Pancreaticoduodenectomy (Whipple procedure) is the standard approach; ampullectomy may be considered for poor surgical candidates.
• Nonsurgical modalities (endoscopic snare resection, laser ablation, photodynamic therapy) offer palliative, not curative, benefits.

Adjuvant Chemotherapy for Ampullary Carcinoma

• Adjuvant chemotherapy may involve infusional 5-FU, gemcitabine, and cisplatin.

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