Pancreatic cancer

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Diagnosis and reasoning

Jaundice is a symptom that often heralds serious underlying disease. Determining whether this is medical (i.e. pre-hepatic or intrahepatic) or surgical (i.e. extrahepatic) is key towards establishing an efficient differential diagnosis. Here, the dark urine suggests at conjugated hyperbilirubinemia; this could be due to either intrahepatic or extrahepatic jaundice. However, the liver profile shows alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) to both be markedly elevated; this strongly favors extrahepatic disease, i.e. obstructive jaundice. The presence or absence of pain is helpful in further narrowing down the differentials of obstructive jaundice. Where pain is present, gallstones and chronic pancreatitis are the two key possibilities. While malignancies typically give rise to painless obstructive jaundice, these should not forgotten, particularly given the loss of >10% of his body weight over just three months. Cancer of the head of the pancreas, cholangiocarcinoma, and metastases to the porta hepatis are key differentials in this regard. As the examination does not provide further clues, ultrasound imaging of the liver and biliary tree is a good next step. This shows the pancreatic duct to be dilated, but the common bile duct to be normal in diameter. This finding is worrisome for a tumor of the head of the pancreas. Note that the pancreas is often obscured by overlying gas from the stomach, duodenum, and colon; therefore, pancreatic masses can be easily missed by abdominal ultrasound, unless quite large. Contrast computed tomography (CT) is a good next step. This confirms the presence of a mass within the head of the pancreas, without local vascular invasion, regional lymphadenopathy, or evidence of distant metastasis. Further imaging via triphasic CT reveals arterial enhancement, a finding supportive of pancreatic adenocarcinoma. Endoscopic ultrasound with fine needle aspiration should follow. The biopsy results confirm the presence of adenocarcinoma. Therefore, this is a T2N0M0 (i.e., stage IB) pancreatic adenocarcinoma. CA 19-9 levels should also be estimated as a baseline. This will be helpful to assess the prognosis and guide the management. Urgent oncology referral is essential. Given the early stage of the tumor, it is possible that neoadjuvant chemotherapy followed by full resection via a pancreatoduodenectomy will be offered. If the patient does not wish to undergo this high-risk surgery, curative ablation of the tumor by endoscopic ultrasound may be attempted instead. ERCP with stenting is a temporary measure to relieve obstructive jaundice, and not suitable here. It is indicated if there is cholangitis that requires urgent decompression, or as a palliative measure, for patients who are not suitable for surgical resection. Pancreatic enzyme supplements (e.g. pancrelipase) are not indicated currently, but may become necessary down the line if he develops pancreatic insufficiency down the line. There is no justifiable indication for corticosteroid therapy.


Discussion

In the United States, pancreatic cancer accounts for 3% of all malignancies diagnosed each year - but for 7% of all cancer-related deaths. It is more common in men, in people over 50 years of age, and in persons of African-American descent. The head of the pancreas is the most frequent site of origin, accounting for 60% to 70% of all cases. Ductal adenocarcinomas are the most common form The cause of pancreatic cancer is unclear. Most cases are sporadic; only 5% to 10% are familial. Many are associated with mutations of the BRCA2 gene. Related conditions include colorectal and ovarian cancer, Peutz-Jeghers syndrome and Li-Fraumeni syndrome. Known modifiable risk factors include smoking, obesity, diabetes mellitus, heavy alcohol intake, a low intake of fruits, and H. pylori infection. The presentation is related to the location of the tumor. Those of the head exert a mass effect on the neighboring structures, leading to abdominal pain, jaundice, dark urine, acholic stools, and pruritus. Tumors of the body or tail present non-specifically, with unexplained weight loss, anorexia, early satiety, dyspepsia, nausea, and depression. Importantly, tumors of the head tend to present relatively earlier than those of the tail. Examination findings are variable. The Courvoisier sign, i.e. a non-tender, distended, palpable gallbladder in a jaundiced patient, is specific but not sensitive for biliary obstruction due to malignancy. Triphasic computed tomography (CT) is the gold standard diagnostic test; a hypoattenuating homogenous mass with indistinct margins in the arterial phase is the typical finding. It is also useful to predict tumor resectability, detect local vessel involvement, and visualize regional lymphadenopathy. If CT is contraindicated, magnetic resonance imaging (MRI) with contrast and/or magnetic resonance cholangiopancreatography (MRCP) is an option, although it is less sensitive and specific for both diagnosis and for assessing tumor invasion. Endoscopic ultrasound is an alternative option for staging. The tumor marker CA19-9 is also often elevated; while of limited diagnostic use, this is helpful to assess the prognosis and guide the management. Where pancreatic cancer is suspected,a multidisciplinary team with both oncological and surgical expertise must be assembled, to identify the most suitable plan of management. Surgical resection is the only curative therapy. Primary lesions without local vascular involvement (i.e. TNM stages IA to IIB) are considered to be fully resectable. Pancreatoduodenectomy is preferred for tumors of the pancreatic head; distal pancreatectomy with splenectomy is performed for tumors of the pancreatic body or tail. Tumor are considered to be borderline resectable (stage III) if local vessel involvement is present. These individuals are recommended to enroll in an ongoing clinical trial if possible. Preoperative neoadjuvant chemotherapy or radiation may be used to increase resectability. Locally advanced cancer refers to locoregionally unresectable tumors without distant spread. Six-month gemcitabine chemotherapy is the standard of care, with or without radiation, followed by re-staging. Concurrent ablation of the tumor may increase survival. Patients with advanced cancer or distant metastases are treated palliatively, with the aim of relieving symptoms caused by the mass, e.g., endoscopic stenting to relieve biliary obstruction. In patients of all stages, oral pancreatic enzyme replacement is recommended to treat exocrine deficiencies. Unfortunately, only 25% of patients are candidates for resective surgery at the time of diagnosis. Even if resection is successful, projected survival is only 12 to 19 months, with five-year survival rates of just 15% to 20%. Overall, only 24% of patients with pancreatic cancer survive for one year, and only 5% survive for five years.


Take home messages

  1. Pancreatic cancer is usually diagnosed at an advanced stage, making this one of the most lethal cancers worldwide; even with optimal chemotherapy, survival is poor.
  2. Triphasic computed tomography (CT) is the gold standard diagnostic test.
  3. Surgical resection is an option for primary tumors with no involvement of the local vessels; however, even afterwards, the prognosis is grim.

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