PANCREAS ALERTS
Lancet 2002; 359:1403-4. (AN 21975535, PMID 11978339 )
Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis.
Hamano H, Kawa S, Ochi Y, Unno H, Shiba N, Wajiki M, et al.
Second Department of Internal Medicine, Shinshu University School of Medicine. Matsumoto, Japan.
Sclerosing pancreatitis is associated with elevated concentrations of IgG4.
The authors treated 22 patients with sclerosing pancreatitis, and identified and followed-up three patients with concomitant hydronephrosis caused by ureteral mass which was later diagnosed as retroperitoneal fibrosis.
At histological examination of the ureteral and pancreatic lesions of these patients, the authors noted an abundant infiltration of IgG4-bearing plasma cells in both tissues. Treatment with corticosteroids lowered serum concentrations of IgG4.
IgG4 might also have a pathological role in a systemic fibrosing process that includes pancreatic and retroperitoneal lesions
J Clin Oncol 2002; 20:3270-5. (AN 22144292, PMID 12149301)
Phase III Study of Gemcitabine in Combination With Fluorouracil Versus Gemcitabine Alone in Patients With Advanced Pancreatic Carcinoma: Eastern Cooperative Oncology Group Trial E2297.
Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB 3rd.
Vanderbilt University. Nashville, TN, USA.
Gemcitabine is generally considered to constitute the first-line therapy for pancreatic cancer.
To determine whether the addition of fluorouracil (5-FU) improves upon the results obtained from single-agent gemcitabine, the Eastern Cooperative Oncology Group (ECOG) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma.
This trial involved patients with biopsy-proven, advanced carcinoma of the pancreas not amenable to surgical resection. Patients were randomized to receive either gemcitabine alone (1,000 mg/m2/wk) weekly for 3 weeks of every 4 or to receive gemcitabine (1,000 mg/m2/wk) followed by 5-FU (600 mg/m2/wk) weekly on the same schedule.
Overall, the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU (P=0.09).
The authors concluded that 5-FU, administered in conjunction with gemcitabine, did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine.
The primary end point of the trial was survival, with secondary end points of time to progression and response rate.
Of 327 patients enrolled over 18 months, 322 were eligible.
Progression-free survival for gemcitabine alone was 2.2 months, compared with 3.4 months for gemcitabine plus 5-FU (P=0.022).
Objective responses were uncommon and were observed in only 5.6% of patients treated with gemcitabine and 6.9% of patients treated with gemcitabine plus 5-FU.
Most toxicities were hematologic or gastrointestinal; no significant differences were noted between the two treatment arms.
Further studies with other combinations of gemcitabine and 5-FU are not compelling, and clinical trial resources should address other combinations and novel agents.
Clin Chem Lab Med 2002; 40:293-7. (AN 21999982, PMID 12005220)
Pancreatic phospholipase A2 activity in acute pancreatitis: a prognostic marker for early identification of patients at risk.
Aufenanger J, Samman M, Quintel M, Fassbender K, Zimmer W, Bertsch T.
Institute for Laboratory Medicine, Clinic Ingolstadt, Teaching Hospital of the Ludwig Maximilians University. Munich, Germany.
Remarkably elevated levels of phospholipase A2 (PLA2) are measurable in human blood samples in cases of acute pancreatitis.
The aim of the study was to evaluate the diagnostic value of PLA2 isoenzyme activity measurements to identify patients with severe complications in acute pancreatitis.
Blood samples from patients suffering from acute pancreatitis were analyzed for catalytically active pancreatic PLA2 on day 1 and 2 of hospitalization with a modified radiometric Escherichia coli-based PLA2 assay.
In 10 of 41 patients clearly elevated values of catalytically active, heat-resistant pancreatic PLA2 (7.2 to 81.2 U/L) were observed. This group of patients was characterized by severe complications (necrotizing pancreatitis, shock, sepsis and respiratory problems) of which two patients subsequently died.
According to these results the presence of catalytically active pancreatic PLA2 in serum is associated with severe complications of acute pancreatitis.
Gastrointest Endosc 2002; 56:202-8. (AN 22140167, PMID 12145597)
Nifedipine for prevention of post-ERCP pancreatitis: a prospective, double-blind randomized study.
Service des Maladies du Foie et de l'Appareil Digestif, INSERM U292, and Laboratoire de Pharmacie, CHU de Bicetre. Le Kremlin-Bicetre, France.
Pancreatitis is the most common complication of ERCP.
The aim of this randomized, placebo-controlled trial was to determine whether the calcium channel blocker nifedipine prevents post-ERCP pancreatitis.
Patients referred for ERCP were enrolled. Those being treated with a calcium channel inhibitor and those with acute or chronic pancreatitis were excluded.
ERCP was unsuccessful in 5 patients. A single case of severe pancreatitis was observed (placebo group).
The study failed to demonstrate a significant effect of nifedipine in the prevention of post-ERCP pancreatitis.
The source of the enzyme was first thought to be exclusively the pancreas, but now it is generally accepted that two isoenzymes - the pancreatic PLA2, group I, and the extrapancreatic PLA2, group II - contribute to the elevated activity.
In contrast to the extrapancreatic group II-PLA2, the pancreatic PLA2 is heat-resistant for 1 hour at 60 °C.
The catalytically inactive proenzyme of the pancreatic PLA2 can be activated by trypsin.
Patients with low or undetectable activity (less than 7 U/L) of pancreatic PLA2 recovered rapidly.
In contrast to total serum-PLA2, the catalytic concentration of pancreatic PLA2 can serve as a prognostic marker in acute pancreatitis.
Prat F, Amaris J, Ducot B, Bocquentin M, Fritsch J, Choury AD, et al.
Calcium channel inhibitors have been shown to prevent the development of experimental pancreatitis.
Nifedipine or a placebo were administered orally less than 3 hours before and within 6 hours after ERCP.
The main outcome measure was the number of cases of post-ERCP pancreatitis; a secondary outcome was the rate of post-ERCP pain without pancreatitis which persisted for 12 or more hours.
One hundred and 55 patients were enrolled and randomized to receive nifedipine (76 patients) or placebo (79 patients). The two groups were comparable.
Procedures performed were retrograde diagnostic cholangiopancreatography alone (n=33), biliary sphincterotomy (n=31), stone extraction (n=39), stent placement (n=37), sphincteroplasty (n=5), and other (n=3).
The rate of post-ERCP pancreatitis was not different between the groups (nifedipine, 10 patients, 13.2%; placebo, 14 patients, 17.7%; p=0.4).
The frequency of post-ERCP pain was not different between the groups.
The only independent predictor of post-ERCP pancreatitis was difficult cannulation in both groups (OR=3.78: 95% CI: 1.25-11.45]).
A multicenter trial with greater statistical power is needed to demonstrate a benefit for this drug.