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Familial pancreatic carcinoma
Familial pancreatic carcinoma is defined by the presence of pancreatic cancer (PC) in two or more first-degree relatives.
ORPHA:1333Classification level: Disorder
The annual incidence has been estimated at approximately 1-10/1,000,000, representing 5-10% of all PC cases.
In familial cases, disease onset occurs before 50 years of age, earlier than for the other forms of PC. A high incidence of familial PC has been observed within hereditary syndromes (Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma syndrome, hereditary breast and ovarian cancer syndrome, and hereditary nonpolyposis colorectal cancer; see these terms). Smoking represents a significant risk factor associated with familial PC. PC can arise from the exocrine (95%) or endocrine portions of the pancreas. In 60% of cases it occurs within the head of the pancreas. The main symptoms are non-specific and include pain in the upper abdomen that typically radiates to the back, loss of appetite, significant weight loss and painless jaundice due to bile duct obstruction. As the clinical course is silent, PC often goes undetected until the advanced stages of the disease. In more than 80% of cases, the cancer is either locally advanced or disseminated at the time of diagnosis. A rapid growth pattern, early vascular dissemination, spread to regional lymph nodes, and metastases to distant organs (liver, peritoneum, lungs) are characteristic. PC can also invade the surrounding visceral organs.
Mutations in the KRAS, CDKN2A, TP53, and SMAD4 genes have been shown to play a role in the etiology of PC. However, they are still not clinically useful for screening or for diagnosing the disease.
Diagnostic methods include ultrasound, contrast-enhanced multidetector computed tomography (MDCT); magnetic resonance (MR) imaging, and integrated positron emission tomography (PET)/computed tomography (CT). Invasive diagnostic techniques are endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound. CA 19-9 is a sensitive tumor serum marker but is not specific.
Differential diagnoses include a wide variety of diseases such as acute and chronic pancreatitis, cholangitis, cholecystitis, cholelithiasis, bile duct tumors and strictures, and gastric cancer and ulcers.
Management and treatment
Surgical resection is the only potentially curative treatment. However, most patients (80%) present with advanced non-resectable tumors. In these cases, chemotherapy (gemcitabine) or radiotherapy, alone or in combination, are alternative treatments, although rather ineffective.
Prognosis is poor (with an overall 5-year survival rate of 5%). Even after complete resection of the tumor, recurrence rates remain high. Patients with a family history of PC should be strongly advised to avoid or cease smoking.