Cancer du pancréas | Clinique Omicron Québec

Histological types

• Pancreatic ductal adenocarcinoma (90-95 %): most frequent malignant tumour of the pancreas - originating from the epithelial cells of the pancreatic ducts; preferential location in the head of the pancreas (60-70 %) where it early obstructs the Wirsung duct and the main bile duct, generating obstructive jaundice; body and tail (30-40 %) - later diagnosis as no early jaundice; molecular profile: mutations of KRAS (90-95 %), CDKN2A/p16 (90 %), TP53 (70-75 %), SMAD4/DPC4 (55 %); dense desmoplastic stroma (60-80 % of tumor volume) - immunosuppressive microenvironment
• Mucinous cystic tumors (MIPCTs and mucinous cystadenomas): tumors with variable malignant potential - mucinous intrapapillary tumors of the pancreas (MIPTs) may be benign (low-risk secondary duct MIPTs) or at high risk of malignant degeneration (main duct or mixed MIPTs - invasive cancer risk of 40-70 %); mucinous cystadenoma mainly affects women; monitoring by pancreatic MRI or echo-endoscopy according to Fukuoka criteria
• Neuroendocrine tumors of the pancreas (NETp) : 3-5 % of pancreatic tumors - derived from islet cells; functional (insulinoma, gastrinoma, glucagonoma, VIPoma) or non-functional (incidental finding or mass) ; significantly better prognosis than ductal adenocarcinoma - 5-year survival of 50-70 % for localized forms; treatment with somatostatin analogues (octreotide, lanreotide), everolimus, sunitinib, lu-DOTATATE (radioligand therapy)
• Acinar cell carcinoma and pancreatoblastoma: rare (< 2 %); pancreatoblastoma is the most common pancreatic malignancy in children

Risk factors

• Smoking: first modifiable risk factor - risk multiplied by 2 to 3 in active smokers; proportional to duration and intensity of smoking; risk gradually decreases after smoking cessation but remains high for 10 to 15 years; responsible for 20-30 % of pancreatic adenocarcinomas
• Long-term type 2 diabetes mellitus : risk multiplied by 1.5 to 2 - insulin resistance and chronic hyperinsulinemia stimulate proliferation of pancreatic ductal cells; to be distinguished from recent inaugural diabetes ( 50 = red flag to be investigated.
• Obesity and sedentary lifestyle: high BMI associated with 1.5-2-fold increased risk - diabetes-like mechanisms (insulin resistance, pro-inflammatory adipokines, IGF-1); abdominal obesity is particularly associated
• Chronic pancreatitis: chronic inflammation of the pancreatic parenchyma - risk multiplied by 5 to 15 depending on severity and duration; alcoholic chronic pancreatitis and hereditary chronic pancreatitis (mutations PRSS1, SPINK1) are the forms most at risk; cumulative risk of pancreatic cancer of 1.5 % at 20 years in chronic pancreatitis of all types combined
• Family history and hereditary syndromes: 10-15 % of pancreatic cancers have a hereditary component - Peutz-Jeghers syndrome (mutation STK11 - relative risk ×132), Lynch syndrome (mutation MMR - risk ×8), FAMMM syndrome (atypical familial melanoma - mutation CDKN2A/p16 - risk ×20-30), mutations BRCA2 (risk ×3-6 - important because sensitive to PARP inhibitors), mutations BRCA1 (risk ×2), hereditary pancreatitis (PRSS1 - risk ×50 at age 70); annual pancreatic MRI screening recommended for people with 2 affected first-degree relatives or an identified hereditary syndrome
• Diet high in saturated fats and processed red meats: moderate association (risk ×1.2-1.5); diet rich in fruit and vegetables and moderate coffee consumption associated with modest risk reduction
• Occupational exposure: organochlorine pesticides, chlorinated solvents, benzidine-based dyes - documented epidemiological associations
• Age: incidence increases with age - rare before age 50, peak incidence between 65 and 80; median age at diagnosis 70

Symptoms

• Painless obstructive jaundice (pancreatic head cancer): progressive jaundice with dark urine (bilirubinuria), discolored stools (acholia), intense skin pruritus - results from compression or invasion of the main bile duct by the cephalic tumor; classic painless character distinguishing it from choledocholithiasis (febrile painful jaundice); Courvoisier-Terrier sign: distended gallbladder palpable without pain in icteric patient = pancreatic head cancer until proven otherwise; present in 60-70 % of head cancers at time of diagnosis
• Abdominal and back pain: dull epigastric pain or abdominal cramps radiating to the back (dorsolumbar region) - results from tumor invasion of the celiac plexus; transfixing character (crossing from the abdomen to the back) typical of cancers of the body and tail ; pain is relieved in some cases by an analgesic position of the trunk forward; symptom present in 70-80 % of cases at diagnosis - often trivialized or attributed to a degenerative pathology of the spine
• Unexplained weight loss and anorexia: often severe involuntary weight loss (5 to 10 kg in a few weeks to months) - linked to malabsorption due to exocrine pancreatic insufficiency (destruction of secretory parenchyma by tumour), paraneoplastic anorexia, pro-cachectising cytokines and reduced food intake due to pain and nausea; present in 80-90 % of cases
• Recent onset of diabetes after age 50: onset of type 2 diabetes with no obvious risk factors in an adult over 50, especially associated with weight loss - a warning sign to look for pancreatic cancer (3-8 % of onset of diabetes after age 50 are linked to underlying pancreatic cancer); mechanism: destruction of endocrine parenchyma by the tumor and release of diabetogenic factors (pancreatic adrenomedullin)
• Deep vein thrombosis and pulmonary embolism (Trousseau syndrome): paraneoplastic hypercoagulability - deep vein thrombosis (DVT) of the lower limbs or pulmonary embolism revealing occult cancer; pancreatic cancer is one of the cancers most frequently associated with thromboembolic events; any unexplained DVT in an adult over 50 years of age warrants an oncological work-up
• Exocrine pancreatic insufficiency: steatorrhea (greasy, voluminous, foul-smelling, difficult-to-rinse stools) and diarrhea - linked to reduced secretion of pancreatic digestive enzymes (lipase, amylase, proteases) due to obstruction of the Wirsung duct or destruction of the parenchyma; malabsorption of fats and fat-soluble vitamins (A, D, E, K)
• Depression and mood disorders: an early and often unrecognized symptom - depression sometimes precedes diagnosis by several months, possibly linked to neurochemical mediators secreted by the tumor; depression should always be investigated for an organic cause in adults over 50 with no psychiatric history
• Acute pancreatitis with no obvious cause: episode of acute pancreatitis in a non-drinker without biliary lithiasis - may reveal a cephalic cancer obstructing the Wirsung duct; any episode of acute pancreatitis with no etiology found in a patient over 50 years of age requires pancreatic MRI after resolution of the acute episode

Diagnosis and extension

• Abdominal CT scan with triphasic injection (pancreas protocol): reference examination for initial diagnosis and staging - arterial, portal and late-phase acquisition to visualize the hypodense tumor in relation to enhanced normal pancreatic parenchyma, assess vascular relationships (superior mesenteric artery, celiac trunk, hepatic artery, superior mesenteric vein, portal vein) to determine resectability, detect hepatic metastases, peritoneal carcinosis and adenopathies; sensitivity of 90-95 % for tumors > 2 cm; limit : isoattenuating tumors < 1-2 cm difficult to identify
• Pancreatic MRI with cholangio-MRI (CPRM) and diffusion sequences: superior to CT for the detection of small tumors (< 2 cm) and TIPMP; assesses dilatation of the duct of Wirsung and the bile ducts (double duct sign - simultaneous dilatation of the pancreatic duct and the main bile duct - highly suggestive of cephalic cancer); diffusion sequences (DWI) improve tumor detection; indispensable for monitoring at-risk cystic pancreatic lesions.
• Echo-endoscopy (EUS) with fine-needle aspiration (EUS-FNA or EUS-FNB): sensitivity of 85-95 % for small tumors; allows histological confirmation (cytopunction or microbiopsy) essential before palliative chemotherapy or neoadjuvant radiochemotherapy; evaluates local extension and vascular involvement; guides biliary or pancreatic drainage and celiac plexus blocks (analgesia).
• FDG PET-CT: detects occult distant metastases not visible on CT in 5-10 % of cases - useful for selecting patients for curative surgery (exclusion of occult metastases); not systematic in first-line treatment
• Tumor markers : CA 19-9 (carbohydrate antigen 19-9) - elevated (> 37 IU/mL) in 70-80 % of advanced pancreatic adenocarcinomas; established prognostic and post-therapeutic follow-up value (doubling of CA 19-9 = probable recurrence) ; low diagnostic specificity (also elevated in benign cholestasis, pancreatitis, other digestive cancers); falsely normal in patients with negative Lewis blood group (10 % of the population - do not secrete CA 19-9); CEA : less sensitive and specific - elevated in 50-60 % of cases; CA-125: may be elevated in forms with peritoneal carcinosis
• Exploratory staging laparoscopy: indicated prior to planned curative surgery to exclude peritoneal carcinosis or superficial liver metastases not detected on imaging - modifies surgical decision in 10-15 % of cases
• CT-guided percutaneous biopsy: not recommended if the tumor is resectable (risk of dissemination along the puncture path and into the peritoneum); indicated only for unresectable or metastatic forms prior to palliative chemotherapy, if EUS-FNA is unavailable or inconclusive

Resectability and staging

Treatment

• Curative surgery (resectable tumors or borderline tumors after neoadjuvant chemotherapy): cephalic duodenopancreatectomy (Whipple procedure) - en bloc resection of the head of the pancreas, duodenum, gallbladder, distal bile duct and part of the stomach (anthrectomy) with reconstruction by triple anastomosis (pancreatojejunostomy, hepaticojejunostomy, gastrojejunostomy) ; distal pancreatectomy + splenectomy (body and tail); total pancreatectomy (rare); vascular resection (superior mesenteric vein or portal vein) in case of moderate venous invasion - possible in expert centers; Whipple surgery: postoperative mortality < 3 % in high-volume centers (≥ 20 DPC/year); specific complications: pancreatic fistula (20-30 %), delayed gastric emptying (15-20 %), postoperative hemorrhage
• Neoadjuvant chemotherapy (selected borderline and locally advanced tumors): modified FOLFIRINOX (folinic acid + 5-FU + irinotecan + oxaliplatin) - 4 to 6 cycles before surgical re-evaluation; allows downstaging with secondary resectability in 15-30 % of locally advanced tumors; gemcitabine + nab-paclitaxel - less toxic alternative; neoadjuvance is increasingly used even for tumors resectable from the outset in reference centers (PREOPANC, NORPACT trials)
• Adjuvant chemotherapy (after R0 or R1 resection) : FOLFIRINOX modified for 6 months - reference adjuvant treatment since the PRODIGE 24/CCTG PA6 trial (median overall survival 54.4 months vs. 35 months with gemcitabine alone); gemcitabine + capecitabine (ESPAC-4) as an alternative for patients unable to tolerate FOLFIRINOX; gemcitabine alone - option for frail patients.
• Palliative chemotherapy (locally advanced unresectable and metastatic) : FOLFIRINOX (folinic acid + 5-FU + irinotecan + oxaliplatin) - median survival 11.1 months vs. 6.8 months gemcitabine alone (PRODIGE 4/ACCORD 11 trial); gemcitabine + nab-paclitaxel (Abraxane) - median survival 8.5 months vs. 6.7 months gemcitabine alone (MPACT trial); second-line: FOLFOX or nanoliposomal irinotecan + 5-FU (Onivyde) after gemcitabine (NAPOLI-1 trial)
• Targeted therapies and immunotherapy according to molecular profile: olaparib (PARP inhibitor) in maintenance for patients with germline mutation BRCA1/2 after stabilization on platinum-based chemotherapy (POLO trial - doubling of progression-free survival); pembrolizumab for MSI-H/dMMR tumours (rare - 1-2 % pancreatic adenocarcinomas); entrectinib or larotrectinib for tumours with fusion NTRK (rare); sotorasib and adagrasib (anti-KRAS G12C) - in active clinical development for rare KRAS G12C mutations (< 2 % of pancreas)
• Radiochemotherapy of locally advanced tumours: gemcitabine or capecitabine + stereotactic ablative radiotherapy (SBRT) or conformal radiotherapy - improved local control in unresectable non-metastatic tumours; radiotherapy in addition to chemotherapy is debated (LAP-07 trial: no benefit in overall survival after induction with gemcitabine ± erlotinib).
• Essential supportive care: endoscopic biliary drainage (self-expanding metal stent - SEMS) for obstructive jaundice; exocrine pancreatic enzymes (pancreatin - Creon) for malabsorption and steatorrhea; celiac plexus block (EUS-guided or percutaneous) for opioid-refractory pain; enteral or parenteral nutrition for severe malnutrition; therapeutic anticoagulation for thrombo-embolic events (cancer associated with a very high risk of VTE); early integrated palliative care.

Consult at Clinique Omicron

Clinique Omicron's physicians assess symptoms suggestive of pancreatic pathology, prescribe the appropriate biological work-up (CA 19-9, hepatic work-up, glycemia, lipasemia) and imaging, and refer without delay to partner gastroenterologists, oncologists and hepatobiliary surgeons, depending on the clinical picture. Consultations are available in our Quebec branches, as well as via telemedicine across the province. To book an appointment, visit cliniqueomicron.ca.

The content of this page is provided for information purposes only and does not replace the advice of a qualified healthcare professional. The diagnosis and management of pancreatic cancer require specialized multidisciplinary evaluation in a digestive oncology referral center.