Chronic Pancreatitis & Pancreatic Cancer 2023 (PDF)

Chronic Pancreatitis  PANCREAS A soft, elongated, flattened gland 12-20 cm in length Situated in the epigastric and left hypochondriac regions of the abdominal cavity FUNCTIONS Digestion of Protein Trypsinogen and Chymotrypsinogen are inactive enzyme precursor...

Chronic Pancreatitis  PANCREAS A soft, elongated, flattened gland 12-20 cm in length Situated in the epigastric and left hypochondriac regions of the abdominal cavity FUNCTIONS Digestion of Protein Trypsinogen and Chymotrypsinogen are inactive enzyme precursors activated by enterokinase to trypsin and chymotrypsin which convert polypeptide to tripeptide and dipeptides. Digestion of Carbohydrates Amylase converts polysaccharides to disaccharides. Digestion of Fats Lipase converts fatts to fatty acids Chronic Pancreatitis- Definition CP is HISTORICALLY defined as an irreversible inflammatory condition of the pancreas, leading to exocrine and endocrine dysfunction RECENTLY, CP is 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 Estimates of annual incidence of CP in several retrospective studies range from 3-9 cases per 100,000 population One prospective study limited to alcoholic CP noted an annual incidence of 8.2 cases per 100,000 and an overall prevalence rate of 35.5 cases per 100,000 A nationwide cross-sectional survey in Japan revealed a male-to- female ratio of 3.5:1 Overall, 10-year survival in CP is about 70% and 20-year survival about 45% Socioeconomic effects One third of chronic pancreatitis patients are unable to persue their professional career The rate of people losing gainful employment due to prolonged periods of 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 CP- TIGAR-O Checklist Clinical manifestation Reccurent episodes of severe and uncontrollable upper abdominal pain Diarrhea/ steatorrhea (loss of exocrine function) Diabetes mellitus ( loss of endocrine function) Abdominal Pain There is no characteristic pain pattern Most commonly described as being felt in the epigastrium Radiation to the back Associated nausea and vomiting Pain may worsen after a meal Nocturnal Relieved by Sitting forward or leaning forward Assuming the knee-chest position Exocrine Insufficiency Steatorrhea Does not occur until pancreatic lipase secretion is reduced to less than 10% A feature of far-advanced CP Maldigestion of fat, protein and carbohydrates Bulky foul-smelling stools Endocrine Insufficiency Diabetes Mellitus Half of patients with CP who develop DM will require insulin DM complications are as common in patients with diabetes associated with CP as in patients with type 1 DM with similar duration of disease The development of DM in CP is most likely related to duration of disease Diagnosis Functional tests Imaging Laboratory studies Functional tests Imaging Imaging role of ERCP ERCP was historically considered the ”gold standard” for the diagnosis of CP Indications include patients for whom CT and MRCP are contraindicated/failed to corroborate the diagnosis Therapeutic modality- such as strictures, stones, pseudocysts and biliary stenosis Imaging EUS EUS has emerged during the past 25 years as the most accurate technique to diagnose in the early stages (high Se) Rosemont criteria for EUS diagnosis in CP Diagnostic algorithm COMPLICATIONS Pseudocyst Debrids and fluid can collect within the pancreas In case of rupture, infection and bleeding can occur Jaundice when located in pancreatic head Pancreatic abscess Cavity of pus within the pancreas Diabetes Due to damage of the insulin producing cells Pancreatic ascites Due to persistent leakage of pancreatic juice from a pseudocyst COMPLICATIONS Pancreatic fistula It is rare Occurs after operative or percutaneous drainage of pseudocyst Malnutrition Due to lack of absorption Splenic vein thrombosis As a result of peripancreatic inflammation TREATMENT Medical Endoscopic Surgical PAIN MANAGEMENT The management of pain in CP can be a challenging problem Stepwise approach to pain Pain- General recommendations Cessation of alcohol Small meals, low in fat Hydration Cessation of smoking Pain- Medical management Pain management should start with non narcotic analgesics NSAIDs should be avoided, use acetaminophen Mostly they fail- it is useful to begin with lower potency opioid agents (tramadol; risk of addiction, abuse and tolerance) Gradually increase the dosage, while focusing the patient on the goal of control of pain to an acceptable level rather than complete relief Pancreatic enzyme supplements Other medical therapies Acid suppression (either with H2 receptor blocker or a PPI) to reduce inactivation of the enzymes from gastric acid Octreotide: not sufficient data Antioxidant therapy: vit C, E, methionine and selenium (limited data)- the mechanism is not fully clear (reduce oxidative stress+ provide antiinflammatory effect) Specialized Approaches Celiac nerve blocks (injections of a local anesthetic-bupivacaine and a steroid; may be performed through endoscopy, interventional radiology or surgery) Endoscopic stenting of the pancreatic duct or pancreatic sphincterotomy Extracoporeal shock wave lithotripsy Surgery Celiac nerve block Endoscopic stenting of the pancreatic duct or pancreatic sphincterotomy SURGERY When the initial medical and endoscopic treatments fail to relieve intractable abdominal pain Indications: Biliary/pancreatic strictres Duodenal stenosis Fistulas Pseudocysts Suspected pancreatic cancer Vascular complications Decompression procedures- Lateral pancreaticojejunostomy Resection TPIAT- Total Pancreatectomy with Islet Auto Transplantation When less invasive treatment options fail Remove the pancreas, either partially or completely; the pancreas is broken down and insulin-producing cells (islets) are isolated; the damaged part of the pancreas is discarded and the islets are transplanted into the liver; the islets begin to function within the liver, helping to prevent diabetes Denervation Procedures PANCREATIC CANCER Introduction Carcinoma of the exocrine pancreas accounts for over 90% of pancreatic tumors and remains an oncologic challenge It is a biologically aggresive tumor from the onset Only 20% of PC are operable for cure Survival: 10-15% at 12 months after diagnosis Surveillance programme: annual EUS or MRI Clinical Presentation Often called the “silent disease” because it usually doesn’t cause symptoms in early stages, therefore DIFFICULT TO DIAGNOSE IN EARLY STAGE When symptomatic: Weight loss Anorexia Nausea and vomiting Abdominal pain Obstructive jaundice- “painless jaundice” (head lesions) New onset/worsening of pre-existing diabetes Investigations Bloods Imaging ESR usually raised CT with iv contrast- identify LFTs may be normal pancreatic mass Abdominal US: often the first test Tumor marker: CA 19-9 (Se+ Sp of to note biliary obstruction 70-90%); can be associated with MRI and MRCP- good for staging benign pancreaticobiliary disease EUS: provides real-time high- as well resolution imaging and image- guided tissue sampling ERCP: it allows for therapeutic interventions (biliary stents placement) Investigations Imaging-CT the main modality for diagnosing PC CT staging: chest, abdomen, pelvis Diagnostic criteria: Hypovascular tumor Indirect signs: main pancreatic and/or common bile duct dilation, segmental atrophy and abnormalities in pancreatic contour Investigations Imaging-MRI: When CT is inconclusive Should include magnetic resonance cholangiopancreatography (MRCP) More sensitive in detecting small liver metastases than CT Imaging reports should detail tumor characteristics, tumor- to-vessel contact for each peripancreatic vessel, locoregional involvement and the presence of distant metastases  Role of Biopsy Biopsy is indicated for patients requiring differential diagnosis with benign chronic pancreatitis or a histological diagnosis before initiating chemotherapy It is not routinely advised if surgical resection is planned EUS-guided fine-needle biopsy is preferred Pathology PCs arise from both the exocrine and endocrine parencyma; however, 95% arise within the exocrine part The most common type: pancreatic ductal adenocarcinoma (PDAC), wich accounts for 80% of PC cases Other variants of PC: Adenosquamous carcinoma Undifferentiated carcinomas with osteoclast-like giant cells Pancreatic acinar-cell carcinomas (better prognosis than PDAC) Pancreatic neuroendocrine tumors Cystic neoplasms: serous cystadenoma/adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm CT scan Treatment Resectability criteria: According to the degree of contact between the tumor and the peripancreatic vessels: Superior mesenteric vein (SMV) or portal vein (PV) Superior mesenteric artery (SMA), celiac trunk and common hepatic artery Tumors are classified as: Resectable Borderline resectable Locally advanced or metastatic CHOLANGIOCARCINOM A Introduction Cholangiocarcinoma (CCA) has been used to refer to bile duct cancers arising in the intra-hepatic, peri-hilar or distal (extra-hepatic) biliary tree Arise from the epithelial cells of the bile ducts Tumors involving the proper hepatic duct bifurcation are referred to as Klatskin tumor or hilar cholangiocarcinoma Epidemiology The incidence of CCA varies across the world It is highest in northeast Thailand Risk Factors for CCA In the majority of cases the etiology of CCA is unknown Several risk factors have been identified Diagnosis Laboratory studies Elevation in TBIL (often >10 mg/dL) and DBIL, ALK phosphatase (2-10-fold UNL) and GGT AST ALT may be normal CCA involving only the intrahepatic ducts are less likely to be jaundiced. Instead they have a history of dull RUQ pain and weight loss and elevated ALK phosphatase Carcinoembryonic Antigen (CEA) is neither sufficiently sensitive nor specific to Dg CCA Cancer antigen (CA) 19-9 is widely used, particularly for detecting CCA in pts with PSC Diagnosis Imaging Contrast CT or MRI: shows arterial and venous enhancement MRCP Cholagiography PTC ERCP Treatment SURGICAL TREATMENT Intrahepatic CCA- > Hepatic segmentectomy or lobectomy Distal extrahepatic CCA -> Pancreatoduodenectomy Hilar CCA -> Biliar duct resection +/- hepatic lobectomy PALLIATION Goal is to decrease pain and jaundice ERCP or percutaneous stent AMPULLARY CARCINOMA General considerations Ampullary carcinomas are defined as those arising within the ampullary complex, distal to the confluence of the distal common bile duct and the pancreatic duct Epidemiology Neoplastic transformation more commonly near the ampulla than at any other site in the small intestine Both benign and malignant ampullary tumors can occur sporadically or in the setting of a genetic syndrome Average age at diagnosis is 60 to 70 years old Clinical manifestations Most common presenting symptom of ampullary carcinoma is obstructive jaundice Additional symptoms: diarrhea due to fat malabsorption, mild weight loss and fatigue Up to one-third of patients have chronic, occult GI blood loss with an associated microcytic anemia Large lesions may produce gastric outlet obstruction associated with severe nausea and vomiting Diagnosis and staging Liver biochemical tests Blood chemistries cannot establish the diagnosis of ampullary carcinoma, but may reflect the presence of cholestasis Aminotransferases may also be elevated The PT may be elevated due to impaired absorption of fat-soluble vitamins including vit K CA 19-9 and CEA non specific Diagnosis and staging Abdominal US First test in patients presenting with obstructive jaundice It will generally not show the tumor Helical CT Scanning should be obtained to visualize the pancreas and surrounding structures ERCP The single most usefull endoscopic study since it permits identification of the tumor, biopsy and decompression if needed EUS It is typically not required for diagnosis Upper GI endoscopy Diagnosis and staging In the absence of metastases, the prognosis of an ampullary carcinoma depends primarily upon two factors: The degree of local tumor invasion The presence of lymphatic spread Prognosis The outcome of resected ampullary cancer depends upon: 1. the extend of local invasion 2. status of the surgical margins 3. the presence or absence of nodal metastases Treatment The only potentially curative treatment for ampullary carcinoma is surgical resection Pancreaticoduodenectomy (Whipple operation) is considered the standard approach for ampullary cancer Ampullectomy is also a reasonable approach for poor surgical candidates Nonsurgical treatment modalities (endoscopic snare resection, laser ablation, photodynamic therapy) provide palliative rather than curative benefit Treatment Adjuvant chemotherapy Infusional 5-FU Gemcitabine cisplatin