Pancreatic Cancer
Predominantly pancreatic ductal adenocarcinoma (over 90% of cases), most often arising in the head of the pancreas.
Risk factors include smoking, chronic pancreatitis, long-standing diabetes, obesity, and hereditary syndromes (BRCA1/2, Peutz-Jeghers, hereditary pancreatitis, Lynch syndrome).
Carries a poor prognosis overall, reflecting typically late presentation and early micrometastatic spread even in apparently localized disease.
Symptoms are often vague and nonspecific until the tumor is locally advanced.
Painless progressive jaundice is classic for head of pancreas tumors, from biliary obstruction; a palpable, nontender, distended gallbladder (Courvoisier's sign) supports malignant rather than gallstone related obstruction.
Other features include epigastric or back pain (suggesting retroperitoneal or neural invasion, generally a marker of advanced disease), unintentional weight loss, new onset diabetes or sudden worsening of previously stable diabetes in an older adult, anorexia, and, less commonly, migratory thrombophlebitis (Trousseau's sign of malignancy).
Body and tail tumors present later, typically with pain and weight loss rather than jaundice, since biliary obstruction is absent.
Contrast enhanced CT pancreas protocol is the primary staging investigation, assessing resectability by evaluating relationships to the superior mesenteric artery, superior mesenteric vein, portal vein, and celiac axis.
CA19-9 is used for monitoring response to treatment rather than diagnosis (it lacks sufficient sensitivity and specificity to screen or diagnose, and can be falsely elevated by biliary obstruction alone).
Endoscopic ultrasound with fine needle aspiration provides tissue diagnosis and assesses vascular invasion with high accuracy. MRCP or ERCP characterizes biliary anatomy and allows stenting for symptomatic jaundice.
PET CT and staging laparoscopy assess for occult metastatic or peritoneal disease before committing to major resection.
Differentials include chronic pancreatitis (particularly autoimmune pancreatitis, which can closely mimic pancreatic cancer radiologically), other periampullary tumors (ampullary, distal cholangiocarcinoma, duodenal), and pancreatic neuroendocrine tumors (distinct biology and management).
Resectable disease (roughly 15 to 20% of cases at diagnosis) is treated with pancreaticoduodenectomy (Whipple procedure) for head of pancreas tumors, or distal pancreatectomy with splenectomy for body and tail tumors, followed by adjuvant chemotherapy (commonly modified FOLFIRINOX or gemcitabine based regimens).
Borderline resectable disease receives neoadjuvant chemotherapy, sometimes with radiotherapy, to downstage before surgery is reconsidered. Locally advanced unresectable disease is treated with systemic chemotherapy, with radiotherapy considered for local control in selected patients.
Metastatic disease is managed with palliative chemotherapy (FOLFIRINOX in fit patients, gemcitabine with nab-paclitaxel as an alternative, or gemcitabine alone in frailer patients), guided by performance status.
Palliative measures address the dominant symptom burden: biliary stenting (endoscopic or percutaneous) for jaundice, duodenal stenting or surgical bypass for gastric outlet obstruction, and aggressive pain control including celiac plexus block for refractory pain.
Pancreatic enzyme replacement is given for associated exocrine insufficiency, and nutritional support is prioritized throughout given the profound catabolic burden of this disease.
Referral: hepatobiliary and pancreatic surgery and oncology multidisciplinary team for all suspected cases at the point of diagnosis, given the narrow and time sensitive resectability window.

