Serum amylase remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis, but its sensitivity can be reduced by late presentation, hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen-2 is convenient, of comparable diagnostic accuracy, and provides greater (99%) negative predictive value. Early prediction of the severity of acute pancreatitis can be made by well validated scoring systems at 48 hours, but the novel serum markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography. For obscure aetiologies, serum calcium and triglycerides should be measured. Genetic polymorphisms may play an important role in "idiopathic" acute recurrent pancreatitis.
Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase -PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) cases, but not in other benign and malignant biliary diseases (Po0.01 and P ¼ 0.06). qPCR revealed a 1.9-fold increased MUC4 mRNA expression in BTC patients' bile compared with benign disease. In archived tissues, MUC4 protein was detected in 37% of BTC but in none of the benign samples (P ¼ 0.03). In serum, MUC5AC was found exclusively in BTC and PSC sera (44% and 13%, respectively; Po0.001 for BTC vs non-BTC) and correlated negatively with BTC survival. Biliary MUC4 and serum MUC5AC are highly specific tumour-associated mucins that may be useful in the diagnosis and formulation of therapeutic strategies in BTC.
Background
There is a need for better management strategies to improve survival and quality of life in patients with biliary tract cancer (BTC).
Aim
To assess prognostic factors for survival in a large, non-selective cohort of patients with BTC.
Method
We compared outcomes in 321 patients with a final diagnosis of BTC (cholangiocarcinoma n=237, gallbladder cancer n=84) seen in a tertiary referral cancer centre between 1998–2007. Survival according to disease stage and treatment category was compared using log-rank testing. Cox regression analysis was used to determine independent prognostic factors.
Results
89 (28%) patients underwent surgical intervention with curative intent, of which 38% had R0-resections. Amongst the 321 patients, 34% were given chemo- and/or radiotherapy, 14% were palliated with photodynamic therapy (PDT) and 37% with biliary drainage procedures alone. The overall median survival was 9 months (3-year-survival 14%). R0-resective surgery conferred the most favourable outcome (3-year-survival 57%). Although patients palliated with PDT had more advanced clinical T-stages, their survival was similar to those treated with attempted curative surgery but who had positive resection margins. On multivariable analysis, treatment modality, serum CA19-9, distant metastasis and vascular involvement were independent prognostic indicators of survival.
Conclusion
In this large UK series of BTC, palliative PDT resulted in similar survival to those with curatively intended R1/R2-resections. Surgery conferred a survival advantage only in patients with R0-resection margins, emphasising the need for accurate pre-operative staging.
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