We searched MEDLINE and PubMed databases for relevant randomised trials and other high-quality studies published from January, 1980, to July, 2015, with the keyword “pancreatic cancer”. We mainly selected publications from the past 5 years, but we did not exclude highly regarded and commonly referenced older publications. Additionally, we searched the reference lists of articles identified by this search strategy and selected those that we judged to be relevant. Review articles and book
SeminarPancreatic cancer
Introduction
Pancreatic cancer is associated with a very poor prognosis, highlighted by the close parallel between disease incidence and mortality.1 5-year survival in patients with pancreatic cancer remains as low as 6% in the USA.2 The low survival rate is attributed to several factors, of which perhaps the most important is the late stage at which most patients are diagnosed. Most patients with pancreatic cancer are asymptomatic until the disease develops to an advanced stage. Up to 20% of patients are eligible for initial resection.2 Even after potential curative resection, most patients will eventually have recurrence, and 5-year survival of completely resected patients is only up to 25%.1 Tumour biology of pancreatic cancer contributes to early recurrence and metastasis, and resistance to chemotherapy and radiotherapy. Autopsy series have shown that about 90% of cases of pancreatic cancer are complicated by distant metastasis.3
To improve prognosis, a screening programme for early diagnosis of pancreatic cancer is needed. Several risk factors for pancreatic cancer, such as a family history of pancreatic cancer,4 as well as personal history of cigarette smoking,5 chronic pancreatitis,6 and diabetes mellitus7, 8 have been identified, but there is currently no standard programme for screening patients at high risk. We review recent developments in the epidemiology, risk factors, pathology, diagnosis, and treatment of pancreatic cancer.
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Epidemiology and risk factors
The American Cancer Society estimates that in 2015, about 49 000 people will be diagnosed with pancreatic cancer in the USA and 41 000 will die of the disease. Pancreatic cancer is the fourth leading cause of cancer death in the USA. Worldwide, pancreatic cancer accounts for more than 200 000 deaths every year. Total deaths from pancreatic cancer are currently increasing and are predicted to be the second leading cause of cancer death in the USA by 2030.9 Increases in pancreatic cancer
Histopathology and molecular pathology
Pancreatic ductal adenocarcinoma is by far the most common pancreatic neoplasm. It is an invasive mucin-producing gland-forming neoplasm that elicits an intense stromal desmoplastic reaction.11 Several histological features can help to diagnose pancreatic ductal adenocarcinoma: haphazard arrangement of glands, nuclear pleomorphism, incomplete glandular lumina, luminal necrosis, neoplastic glands immediately adjacent to muscular vessels, perineural invasion, and lymphovascular invasion (figure 1
Clinical presentation, signs, and symptoms
Most pancreatic cancers have no symptoms in the early stage. A large case-control study comparing the incidence of early pancreatic cancer symptoms suggested that pancreatic cancer is associated with 12 alarm symptoms: weight loss, abdominal pain, nausea and vomiting, bloating, dyspepsia, new-onset diabetes, changes in bowel habit, pruritus, lethargy, back pain, shoulder pain, and jaundice.43 Back pain (odds ratio [OR] 1·33 [95% CI 1·18–1·49]), lethargy (OR 1·42 [1·25–1·62]), and new-onset
Serum tumour markers
The combination of serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA)48, 49, 50 has been reported to decrease sensitivity to 37%, but increase specificity to 84% compared with CA19-9 alone, for diagnosis of pancreatic cancer.51 A recent study has shown that a serum protein biomarker panel consisting of CA125, CA19-9, and laminin γC (LAMC2) can significantly improve performance in detecting pancreatic cancer compared with CA19-9 alone under several conditions (ie, all
Differential diagnosis from autoimmune pancreatitis
Mass-forming pancreatitis and other pancreatic malignancies such as malignant lymphoma should be differentiated from pancreatic cancer. Most cases of mass-forming pancreatitis are autoimmune pancreatitis, which is divided into two subtypes. Type 1 autoimmune pancreatitis, the most common form, is characterised by the histological feature of lymphoplasmacytic sclerosing pancreatitis and is considered to be a pancreatic lesion of IgG4-related disease. Type 2 shows the histological feature of
Treatment
Treatment of pancreatic cancer includes surgery, chemotherapy, radiation therapy, and palliative care. The treatment options are selected depending on the stage of pancreatic cancer in a multidisciplinary approach (figure 5). Treatment of IPMN and MCN is reviewed elsewhere.85
Future perspectives
Screening programmes in high-risk individuals including familial pancreatic cancer kindreds are expected to yield more patients with pancreatic cancer at an early stage.111
There are several directions for future studies on pancreatic cancer. First, the correlation of genetic alterations with clinically important features, such as pattern of recurrence and response to chemotherapy, will facilitate the translation of these findings into clinically useful assays. The Individualized Molecular
Search strategy and selection criteria
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