Associations between EBV serostatus and organ transplant type in PTLD risk: an analysis of the SRTR National Registry Data in the United States.

In a prior multiorgan transplant database study, recipient Epstein-Barr virus (EBV) seronegativity was not associated with increased risk for posttransplant lymphoproliferative disorders (PTLD) in liver transplants (LTX), at variance with prior single center reports and with data from kidney and heart transplants (KTX and HTX). The Scientific Registry of Transplant Recipients (SRTR) in the United States is the only other registry with data on the required variables for comparison.Our study set comprised 112 756 KTX (580 PTLDs; 0.51%), 13 937 HTX (140 PTLDs; 1.0%) and 40 437 LTX (383 PTLDs; 0.95%) performed January 2003 onward. The unadjusted hazard ratio (HR) for PTLD if recipient EBV seronegative was 5.005 for KTX, 6.528 for HTX and 2.615 for LTX (p < 0.001 for all). In models adjusted for multiple covariates, the adjusted HR was 3.583 (p < 0.001) for KTX, 4.037 (p < 0.001) for HTX, 1.479 (p = 0.03) for LTX. Interaction models using EBV seropositive KTX as reference group showed significantly higher risk for all other EBV seronegative organ transplant groups and also for EBV seropositive LTX (AHR 2.053, p < 0.0001).Recipient EBV seronegativity is still significantly associated with risk for PTLD in LTX, though less so because of higher baseline risk in the EBV seropositive LTX group.

Effects of exogenous secretin on pancreatic and biliary ductal and sphincteric pressures in man demonstrated by endoscopic manometry and correlation with plasma secretin levels.

An endoscopic manometric technique was used to investigate the effects of exogenous secretin on pancreatic duct, common bile duct, pancreatic duct sphincter, and bile duct sphincter pressures in 20 healthy volunteers. Synthetic secretin was infused intravenously at rates of 8.05, 16.1, 32.2, 64.4, 129, 258, and 516 ng/kg/hr, and plasma secretin concentrations were measured by a radioimmunoassay. Secretin produced a significant fall in peak and trough pancreatic duct sphincter pressures from basal values of 48.2 +/- 7.9 mm Hg (mean +/- SD) and 16.9 +/- 7.7 mm Hg, respectively, to 34.4 +/- 6.8 mm Hg and 11.2 +/- 5.8 mm Hg (P less 0.005), respectively, at a mean plasma secretin concentration of 16 pg/ml (during an infusion rate of 32.2 ng/kg/hr). Higher infusion rates had no additional effect. Pancreatic duct pressure became significantly elevated above basal (11.5 +/- 4.0 mm Hg) at the two highest secretin rates. Secretin had no effect on common bile duct or bile duct sphincter pressures. Plasma secretin concentrations were within the postprandial range during the lowest four secretin infusion rates. We conclude that secretin produces selective physiological relaxation of the pancreatic duct sphincter.

Secretion of beta-lactam antibiotics in pure human pancreatic juice.

The secretion of cephalothin and cefoxitin in stimulated pure pancreatic juice was studied in 13 persons after intravenous administration of antibiotics. Of all these studied, three had acute relapsing pancreatitis, five chronic pancreatitis, and five were control subjects. Antibiotic levels were measured in paired pure pancreatic juice and serum samples at fixed time intervals after administration. Cephalothin was detected in very low levels (1 to 1.8 micrograms/ml) in the pure pancreatic juice of four of the six persons studied (3 micrograms/ml). Although therapeutic levels were not obtained in stimulated pure pancreatic juice with either antibiotic, additional studies evaluating antibiotic levels in unstimulated pure pancreatic juice and in pancreatic tissue would be helpful in assessing the role of antibiotic therapy in the treatment of pancreatitis.

Sphincter of Oddi stenosis: diagnosis using hepatobiliary scintigraphy and endoscopic manometry.

To determine the role of radionuclide imaging in diagnosing sphincter of Oddi stenosis, 21 patients with symptoms suggesting this disorder underwent endoscopic retrograde cholangiopancreatography, cholescintigraphy, and, when possible, endoscopic manometry. Those patients with abnormal hepatobiliary scintigraphy results--based on our criteria of delayed biliary intestinal transit, abnormal duct size, and abnormal time-activity dynamics and obstruction--had a mean basal sphincter pressure of 38.5 mm Hg. Sphincter pressures could not be measured in six patients with sphincters too tight to cannulate. Ten patients who underwent hepatobiliary scanning both before and after sphincter surgery had normal scan results on the repeat study. Hepatobiliary imaging appears useful for diagnosis of sphincter of Oddi stenosis in selected patients in whom manometry cannot be performed and for objective assessment of response to therapy.

Effects of sphincteroplasty and endoscopic sphincterotomy on the bacteriologic characteristics of the common bile duct.

Forty-five patients with sphincter of Oddi stenosis had specimens of common bile duct cultured during ERCP before either sphincteroplasty or endoscopic sphincterotomy. All had sterile bile before sphincter ablation. Bile was recultured 6 to 36 months later during endoscopy at which time 70 percent of the sphincterotomy and 76 percent of the sphincteroplasty patients had bile colonized principally by enteric organisms. Growth was heavy to moderate in most of the patients and contained few nasopharyngeal organisms. Despite bactobilia, no patient had symptomatic cholangitis, presumably due to excellent drainage of bile. The most likely source of the bactobilia is from direct extension of duodenal organisms into the common bile duct.

Endoscopic pancreatic and biliary manometry in pancreatic, biliary, and papillary disease, and after endoscopic sphincterotomy and surgical sphincteroplasty.

Endoscopic manometry was used to measure pancreatic duct, common bile duct, pancreatic duct sphincter and bile duct sphincter pressures in 43 healthy volunteers and 162 patients with a variety of papillary, pancreatic and biliary disorders. Common bile duct pressure was significantly raised after cholecystectomy, with common bile duct stones and papillary stenosis but pancreatic duct pressure only in papillary stenosis. After endoscopic sphincterotomy mean common bile duct pressure fell from 11.2 to 1.1 mmHg and pancreatic duct pressure from 18.0 to 11.2 mmHg. Distinct pancreatic duct sphincter and bile duct sphincter zones were identified as phasic pressures of 3-12 waves/minute on pull-through from pancreatic duct and common bile duct to duodenum. Pancreatic duct sphincter pressures were higher with common bile duct stones and stenosis whereas bile duct sphincter pressures were higher in pancreatitis and stenosis. Bile duct sphincter activity was present in 60% of patients after surgical sphincteroplasty but 21% of patients after endoscopic sphincterotomy. Endoscopic manometry facilitated the diagnosis of papillary stenosis, has allowed study of papillary pathophysiology and has shown a functional inter-relationship between the two sphincteric zones.

Rhythm abnormalities of the biliary and pancreatic sphincters: diagnosis by endoscopic manometry.

Abnormal phasic wave activity was noted in the biliary duct sphincter, pancreatic duct sphincter, or both in 43 patients. This abnormality consisted of a tachyrhythmia in 40 patients and absent phasic wave activity in 3 patients. Tachyrhythmia was encountered in patients with elevated basal sphincter pressures. In four patients with tachyrhythmia, administration of intravenous naloxone failed to modify phasic wave activity. Three patients with normal basal sphincter pressures had absent phasic wave activity. This abnormality occurred in two patients with cirrhosis and in one patient with suspected cirrhosis. In one patient with cirrhosis, administration of intravenous morphine did not induce phasic wave activity.

Effects of exogenous glucagon on pancreatic and biliary ductal and sphincteric pressures in man demonstrated by endoscopic manometry and correlation with plasma glucagon.

An endoscopic manometric technique was used to investigate the effects of glucagon on pancreatic duct, common bile duct, pancreatic duct sphincter, and bile duct sphincter pressures in 20 healthy volunteers. Glucagon was given by intravenous infusion at rates of 0.016, 0.0625, 0.25, 1.0, 4.0, and 16.0 micrograms/kg/hr and also as an intravenous bolus of 1 mg. Plasma glucagon was measured by radioimmunoassay. Glucagon significantly reduced peak bile duct sphincter pressure from 49.1 +/- 3.7 mm Hg (mean +/- SD) to 37.8 +/- 2.9 mm Hg (P less than 0.01) at a rate of 0.016 microgram/kg/hr, reaching a maximum effect at rates of 0.25 microgram/kg/hr and above. Reduction in pancreatic duct sphincter, pancreatic duct, and bile duct pressures; slowing of sphincter wave frequency; and shortening of wave duration occurred at infusion rates of 1.0 microgram/kg/hr or greater when plasma concentrations were supraphysiological. We conclude that glucagon has a physiological action on the bile duct sphincter but that all other effects on this area are pharmacological.

Pancreas divisum. Results of surgical intervention.

The embryologic defect that results when the ventral and dorsal anlages of the pancreas do not fuse has been referred to as pancreas divisum. ERCP has made it possible to recognize this anomaly in patients undergoing investigation for otherwise unexplained abdominal pain. Of 70 patients in whom recurrent epigastric pain and pancreas divisum coexisted, sphincteroplasty of both papillae was carried out in 19 because of intractability of symptoms. In six patients, surgery was performed subsequent to failure of other biliary tract surgery. There was one postoperative death. In the remaining 18 patients, initial results were good to excellent in 13 and fair in 1. In four patients, however, recurrence of symptoms developed within periods that ranged from 1 to 6 months; therefore, reasonably permanent relief was limited to 10 patients. Of the remaining eight patients with recurrent or continuing symptoms, a variety of subsequent procedures led to satisfactory results in only three. In only seven patients was there even minimal chemical or microscopic evidence to suggest active pancreatitis. Similarly, pancreatograms in 17 patients with this anomaly revealed no abnormalities except for minor ones in 2 patients. Thus, if this is a syndrome that is due to relative stenosis of the lesser papilla and duct, the anomaly does not often result in documented pancreatitis. The definite but limited success rate from sphincteroplasty suggests that relative stenosis of the lesser papilla may be the cause of a syndrome but surgical refinements will be necessary to achieve a better operative success rate.

The intraductal secretin test: an adjunct to ERCP.

The intraductal secretin test is an important diagnostic study. It enables the physician to determine the pancreatic secretory function in patients with known pancreatitis and to confirm the diagnosis of pancreatitis in many patients with indeterminate upper abdominal pain in whom ERCP and other diagnostic studies are normal. The IDST also provides the endoscopist and biochemist a new means to establish discriminating tests in differential diagnosis of pancreatic cancer and pancreatitis and to study the physiology of pancreatic secretion.

Importance of common bile duct stricture associated with chronic pancreatitis. Diagnosis by endoscopic retrograde cholangiopancreatography.

Twenty-one patients with common bile duct strictures associated with chronic pancreatitis are described in whom ERCP was the principal diagnostic method used. In 5 of the 11 patients who had had previous pancreatic or biliary surgery, a common bile duct stricture was overlooked. Nine patients had one or more attacks of cholangitis which were severe in seven and caused death in one. Endoscopically aspirated bile cultures showed heavy gram-negative infection in four patients with previous cholangitis. Two patients developed stones above the strictures, and in one this led to obstruction of a previous cholecystjejunostomy. Although strictures may be discovered at an asymptomatic stage, there should be careful follow-up to detect the appearance of any symptoms or objective signs of stricture progression, when surgery should be offered without delay. Direct biliary-enteric anastomosis is the procedure of choice when possible to relieve symptoms and prevent the potentially life-threatening complications of cholangitis and septicemia.

Endoscopic manometry of pancreatic and biliary sphincter zones in man. Basal results in healthy volunteers.

An endoscopic manometric technique was applied to the study of intraductal biliary and pancreatic pressures and sphincter activity in normal subjects. A perfused system using a modified endoscopic retrograde cholangiopancreatography catheter was tested and found to provide reliable ductal and phasic recordings. Twenty-five healthy volunteers, aged 19-37, underwent endoscopic manometry under diazepam sedation. Distinct zones of high-pressure phasic activity were identified on pull-through from the pancreatic duct and common bile duct at mean distances of 4.5 and 5.0 mm, respectively, from the papillary orifice with frequencies of 7.0 +/- 1.8 (mean +/- SD) and 5.6 +/- 2.4 waves/min, respectively. These were considered to represent separate pancreatic duct and bile duct sphincters. Peak pancreatic duct sphincter pressure (47.6 +/- 8.2 mm Hg) and bile duct sphincter pressure (57.2 +/- 10.7 mm Hg) were similar. Pancreatic duct pressure was 11.4 +/- 3.0 mm Hg and common bile duct pressure was 3.0 +/- 2.5 mm Hg. Values were adjusted to duodenal pressure as zero reference. The ductal and sphincteric pressures reported in this study provide a basis for the assessment of physiological, pharmacological, pathophysiological, and surgical effects on this area.

Postcholecystectomy syndrome and its association with ampullary stenosis.

Fifty-six consecutive patients returning with recurrent or persistent upper abdominal pain after cholecystectomy were studied by endoscopic retrograde cholangiopancreatography, abdominal ultrasound and morphine neostigmine test. In 44 patients, pain recurred within 6 months after cholecystectomy. Forty patients were demonstrated on endoscopic retrograde cholangiopancreatography to have moderate to marked ampullary stenosis, which occurred as an isolated abnormality in 32 patients and in association with pancreatitis in 8. Thirteen patients were found to have pancreatitis, and 6 had retained common duct stones. In five patients no definite abnormality was demonstrated. The morphine neostigmine test was positive in 16 of 17 patients with isolated ampullary stenosis and in only 1 of 8 with pancreatitis. This test may be helpful in patients who are to undergo cholecystectomy. In those with positive results, endoscopic retrograde cholangiopancreatography would help assess the size of the ampullary sphincter so that sphincteroplasty could be done at the time of cholecystectomy in appropriate patients.

Endoscopic retrograde cholangiopancreatography and gray-scale abdominal ultrasound in the diagnosis of jaundice.

Fifty-five patients with suspected obstructive jaundice were studied with both ERCP and abdominal ultrasound. Biliary tract obstruction was documented in 49 patients and parenchymal liver disease in 7. A definite cause of jaundice was demonstrated by ERCP in 45 of 49 patients with biliary tract obstruction but in only 28 of 49 patients by ultrasound. Bile duct dilatation, where present, was detected by ERCP in only 33 of 42 patients. ERCP was particularly effective in patients with common duct stones; common duct calculi and a dilated common duct were detected in 15 of 16 such patients. Dilated bile ducts where present were detected by ultrasound in 22 of 42 patients. Ultrasound was particularly helpful in patients with pancreatic cancer in whom a dilated common duct could not be opacified during ERCP. ERCP and abdominal ultrasound together provide a rapid and safe method of diagnosis in the jaundiced patient with suspected bile duct obstruction.

Endoscopic measurement of pancreatic juice secretory flow rates and pancreatic secretory pressures after secretin administration in human controls and in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer.

Secretory flow rates were measured inside the main pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer and in controls after intravenous administration of secretin. Peak secretory flow rates in these groups were 5.04 +/- 1.74, 0.71 +/-1.28, 0.60 +/- 1.37, and 4.13 +/- 0.88 ml/min, respectively. Peak secretory pressures were also measured intraductally in patients with acute relapsing pancreatitis and pancreatic cancer and in controls and were 402 +/- 69, 75 +/- 161, and 403 +/- 99 mm pancreatic juice, respectively. Peak secretory flow rates and pressures measured in controls during constant administration of secretin were similar to those measured when secretin was administered as a bolus.

Pancreatic hypersecretion in liver disease.

Abnormally large duodenal aspirates have been reported in a large percentage of patients with cirrhosis of the liver. The source of this fluid has been variously ascribed to the liver and/or pancreas. The present study was undertaken to clarify its source. Eleven patients with cirrhosis of the liver and one with cholestatic hepatitis underwent an intraductal secretin test during endoscopic cannulation of the pancreatic duct. Six patients with cirrhosis had pancreatic hypersecretion ranging from 7.8 to 26.0 ml/min, while three patients demonstrated low secretory flow rates. Bile flow was negligible or nonexistent in ten patients, while in two others, larger but unmeasurable amounts of bile secretion were present. This study conclusively demonstrates that pancreatic hypersecretion may occur in patients with cirrhosis during secretin stimulation. Impaired metabolism of secretin or the associated pancreatic hypersecretion of early pancreatitis may be responsible for this finding.

Detection of bacterial infection of the pancreatic ducts in patients with pancreatitis and pancreatic cancer during endoscopic cannulation of the pancreatic duct.

Bacterial infections of the pancreas and bacteremia may occur during episodes of pancreatitis. Detection of bacterial infections of the pancreas in the past has required laparotomy. The present study was undertaken to determine whether bacterial infection of the pancreas occurred during nonsuppurative pancreatitis. During endoscopic cannulation of the main pancreatic duct, secretin was administered intravenously and pancreatic juice aspirated from within the duct was cultured. Bacterial infections were detected in 11 of 35 patients with pancreatitis and 3 of 5 with pancreatic cancer. The pancreatic juice was sterile in 25 controls. Cultures from the common bile duct in 9 controls were also sterile whereas 4 of 6 with pancreatitis showed infected bile. The infecting organisms were principally gram-negative and the infections were usually polymicrobial. Antibiotics, where used, successfully eradicated the infecting organisms but did not appear to affect the patient's clinical course.

Pancreas divisum: its association with pancreatitis.

Thirty-three patients with pancreas divisum studied by endoscopic retrograde cholangiopancreatography (ERCP) are described. Documented pancreatitis was present in fifteen patients, and another eleven had recurrent episodes of pain typical of pancreatitis. The major papilla was cannulated in all patients, but the duct of Wirsung was opacified in only twenty-eight and showed changes of pancreatitis in one. Attempts were made to cannulate the minor papilla in fifteen of the thirty-three patients and were successful in four. The duct of Santorini showed typical changes of pancreatitis in one. One patient had pancreatic cancer, and the duct of Wirsung demonstrated only nonspecific abnormalities. In only two cases was pancreatitis due to alcohol abuse. The high incidence of pancreatitis and pancreatic-like pain in patients with pancreas divisum, may be due to the very small ampulla of the duct of Santorini which in these patients drains the majority of the pancreas, creating a marked relative stenosis of the ampulla. Surgery for relief of pain was required in five patients. The operation of choice, when pancreatitis involves the dorsal pancreas, appears to be distal resection with drainage.

Duodenoscopy and endoscopic pancreatography in patients with postive morphine prostigmine tests.

Twenty-three patients with abdominal pain and positive morphine prostigmine tests underwent duodenoscopy and endoscopic retrograde cholangiopancreatography (ERCP). Sixteen demonstrated marked or moderate ampullary stenosis. The pancreatic duct was dilated in three and stenotic in four. Ampullary stenosis was confirmed in all patients who subsequently underwent sphincteroplasty. Only six patients had pancreatitis demonstrated by appropriate laboratory studies or at surgery. Relief of pain after sphincteroplasty was complete in ten patients during follow-up.