Biomedical subjects
Publications and source records attributed to E L Fogel.
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AIM: To review the computed tomography (CT), magnetic resonance imaging (MRI) and cholangiographic findings of chemotherapy-induced sclerosing cholangitis (CISC). METHODS: Between January 1995 and December 2004, 11 patients in the endoscopic retrograde cholangiography database were identified with CISC. Twelve CT, four MRI, 69 endoscopic and nine antegrade cholangiographic studies in these patients were reviewed. Serial change in appearance and response to endoscopic treatment were recorded. RESULTS: CISC showed segmental irregular biliary dilatation with strictures of proximal extrahepatic bile ducts. The distal 5cm of common bile duct was not affected in any patient. CT and MRI findings included altered vascular perfusion of one or more liver segments, liver metastases or peritoneal carcinomatosis. Biliary strictures needed repeated stenting in 10 patients (mean: every 4.7 months). Cirrhosis (n=1) or confluent fibrosis (n=0) were uncommon findings. CONCLUSION: CISC shares similar cholangiographic appearances to primary sclerosing cholangitis (PSC). Unlike PSC, biliary disease primarily involved ducts at the hepatic porta rather than intrahepatic ducts. Multiphasic contrast-enhanced CT or MRI may show evidence of perfusion abnormalities, cavitary liver lesions, or metastatic disease.
BACKGROUND AND STUDY AIMS: The development of anastomotic strictures is one of the most common complications of orthotopic liver transplantation (OLT) with choledochocholedochostomy anastomosis. Endoscopic therapy with balloon dilation and/or stent placement is an effective therapy. The aim of this study was to assess the recurrence rate of anastomotic strictures and the features that predict recurrence after previously successful endoscopic therapy. PATIENTS AND METHODS: We searched the endoscopic retrograde cholangiopancreatography (ERCP) database for all patients who had had an OLT who were undergoing ERCP. The study cohort consisted of post-OLT patients who had a recurrence of anastomotic stricture after initial resolution following a course of endoscopic therapy. RESULTS: A total of 916 OLT operations were performed during the study period from June 1994 to November 2004. Out of this group, 143 patients (15.6 %) were diagnosed with anastomotic stricture and underwent a total of 423 ERCPs for endoscopic treatment. Twelve patients who are still undergoing endoscopic therapy were excluded from the analysis. The technical success rate was 96.6 %, and the endoscopic therapy was successful in 82 % of patients; 18 % had a recurrence of cholestasis and ERCP revealed a recurrence of the anastomotic stricture that required intervention. The mean time of follow-up after stent removal was 28 months (range 1 - 114 months). The study did not reveal any clinical or endoscopic parameters that could predict recurrence, though the presence of a biliary leak at initial ERCP and a longer time to initial presentation were factors that showed a trend toward an increased likelihood of recurrence. CONCLUSIONS: Biliary strictures remain a common complication after OLT, and in nearly one in five patients these strictures recur after initially successful endoscopic therapy. There were no clinical or endoscopic parameters identified in this study that predicted recurrence. Further study is needed to determine what type of endoscopic therapy would minimize the risk of stricture recurrence.
Some steps of progress have been seen in the area of biliary therapeutic endoscopy, in the understanding and management of primary sclerosing cholangitis, problems relating to liver transplantation, malignant biliary strictures, and complications after endoscopic retrograde cholangiopancreatography, as well as sphincter of Oddi dysfunction. These topics are reviewed here.
Some steps of progress have been seen in the area of biliary therapeutic endoscopy, in the understanding and management of primary sclerosing cholangitis, problems relating to liver transplantation, malignant biliary strictures, complications after endoscopic retrograde cholangiopancreatography, sphincter of Oddi dysfunction, and tissue sampling. The benefits (or lack thereof) of preoperative biliary drainage in the setting of malignant obstructive jaundice have received an extensive review.
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BACKGROUND AND STUDY AIMS: Patients with suspected or documented sphincter of Oddi dysfunction (SOD) who undergo standard biliary sphincterotomy have high rates of post-procedure pancreatitis. Approximately 75% of such patients have elevated basal pressures of the pancreatic sphincter. Biliary sphincterotomy (BES) on its own leaves the pancreatic sphincter unablated and may cause transient edema which aggravates the increase in pancreatic sphincter pressure. Combined pancreaticobiliary therapy (PBR), using pancreatic stenting in addition to sphincterotomy may therefore be safer. PATIENTS AND METHODS: The endoscopic retrograde cholangiopancreatography (ERCP) database was queried for patients with successful double-duct sphincter of Oddi manometry (SOM) who underwent BES alone or PBR between 1994 and 1997. The endoscopist had decided on the technique to be used. From 1995 to 1997 there was a general trend to do PBR. Pancreatitis was defined according to established criteria. RESULTS: The post-ERCP pancreatitis rate among all 436 SOD patients was 19.7%, while 256 patients with normal SOM results had a pancreatitis rate of 12.9%. The use of combined PBR was associated with a lower frequency of pancreatitis compared with BES alone (needle-knife over pancreatic duct stent, 14/131 patients, 10.7 %; pull-type pancreaticobiliary sphincterotomy plus pancreatic stent, 15/78 patients, 19.2%; BES alone, 52/184 patients, 28.3%). Episodes of moderate and severe pancreatitis were seen more frequently in the BES group. CONCLUSION: In SOD patients, post-ERCP pancreatitis rates remain high, but have improved with the addition of combined pancreaticobiliary sphincter therapy.
Therapeutic biliary endoscopy is continuing to evolve; some small but important developments were seen during the last year. Competing techniques are continuing to develop.
BACKGROUND: Procurement of cytologic samples by brushing is common practice at endoscopic retrograde cholangiopancreatography (ERCP) but has low sensitivity for cancer detection. Limited data are available on other techniques, including endoluminal fine-needle aspiration and forceps biopsy. This series reviews the yield of these three stricture sampling methods. METHODS: In this prospective study, patients with biliary obstruction with a clinical suspicion of malignancy underwent triple-tissue sampling at one ERCP session. Final cancer diagnosis was based on all sampling methods plus surgery, autopsy, and clinical follow-up. Tissue specimens were reported as normal, atypia, or malignant. RESULTS: A total of 133 patients were evaluated: 104 had cancer and 29 had benign strictures. Tissue sampling sensitivity varied according to the type of cancer; the highest yield was seen in ampullary cancers (62% to 85%). The cumulative sensitivity of triple-tissue sampling in the cancer patients was as follows: sensitivity was 52% if atypia was considered benign and 77% if it was considered malignant. The addition of a second or third technique increased sensitivity rates in most instances. No serious complications occurred from the tissue sampling methods. CONCLUSIONS: Tissue sampling sensitivity varied according to the type of cancer. Combining a second or third method increased sensitivity; general use of at least two sampling methods is therefore recommended.
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BACKGROUND: The diagnostic and therapeutic success of endoscopic retrograde cholangiopancreatography (ERCP) depends on a number of factors. When an attempt at ERCP fails, the physician must decide whether to repeat the procedure, rely on another imaging procedure (noninvasive or invasive), or refer to another endoscopist/center. Our aim in this prospective study was to determine the role of a second attempt at ERCP at a referral ERCP center. METHODS: Five hundred sixty-two patients were referred for ERCP after having undergone a previous unsuccessful attempt to visualize the clinically relevant duct(s). RESULTS: The overall success in visualizing the desired duct was 96.4% (542 of 562). Advanced techniques for cannulation were used in 41% (229 of 562). Anatomic abnormalities possibly contributing to the previous lack of success were present in 27% of cases. ERCP with or without manometry identified a cause or potential cause for the signs and symptoms in 86% of patients. Sixty complications occurred in 57 patients (10.1%). ERCP was unsuccessful in 20 patients (3.6%). CONCLUSIONS: The cannulation success rate and diagnostic yield of further ERCP with an acceptable complication rate warrant consideration of referral to centers with available resources and expertise.
BACKGROUND: Sphincter of Oddi manometry as performed at ERCP is the most accepted method to evaluate for sphincter of Oddi dysfunction. To fully assess for sphincter of Oddi dysfunction, both the pancreatic and the bile ducts must be evaluated. We assessed the frequency of pancreatic and biliary sphincter abnormalities in a large series of patients. METHODS: A total of 593 patients underwent manometry of the biliary and pancreatic ducts at one endoscopic retrograde cholangiopancreatography session. Basal sphincter pressure greater than or equal to 40 mm Hg was considered abnormal. Phasic waves were not evaluated. Manometric abnormalities were correlated with the clinical presentation as categorized using a modified Geenen/Hogan classification. RESULTS: Of 360 patients with intact sphincters, 18.9% had abnormal pancreatic sphincter basal pressure alone, 11.4% had abnormal biliary basal sphincter pressure alone, and in 31.4% the basal pressure was abnormal for both sphincters; thus, 60.1% of the patients had sphincter dysfunction. The frequency of sphincter of Oddi dysfunction did not differ whether typed by biliary or pancreatic criteria: approximately 65% type II and 59% type III. Of patients without pancreatitis, 55.9% had an abnormal basal sphincter pressure, whereas sphincter dysfunction was present in 72.3% of those with idiopathic pancreatitis and 53.9% of patients with chronic pancreatitis. Of patients with an ablated biliary sphincter, 45.9% had abnormal basal pancreatic sphincter pressure and only 0.6% had an abnormal biliary sphincter pressure alone. Abnormal pressure in both sphincters was found in 9.3%. CONCLUSION: If both portions of the sphincter of Oddi are studied simultaneously, abnormalities are found very commonly (55% to 72%). Assessment of both sides of the sphincter is necessary. Classifying patients according to both pancreatic and biliary sphincter segments is cumbersome, and may be replaced by an overall type. Using this modified classification, the frequency of sphincter of Oddi dysfunction is similar in both type II and type III patients (59% to 67%).
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BACKGROUND: Selective biliary cannulation is often difficult when there is a periampullary diverticulum, especially when the papilla is within the diverticulum. We report eight such cases in which a new technique was used to achieve biliary access. METHODS: Among 4138 ERCPs, there were 246 cases (5.9%) with periampullary diverticula. Biliary cannulation initially failed in eight patients (3.3%), five of whom had previously undergone six failed attempts at other institutions. A technique was used whereby the papilla was kept out of the diverticulum by placement of a pancreatic duct stent. Needle-knife sphincterotomy was then performed followed by attempts to achieve biliary access. RESULTS: Biliary entry was immediately successful in five patients and successful at a second ERCP in two (overall success 87.5%). Two patients developed post-ERCP pancreatitis. CONCLUSIONS: When the papilla is within the periampullary diverticulum, placement of a main pancreatic duct stent keeps the papilla out of the diverticulum, thereby facilitating pre-cut needle-knife sphincterotomy and selective biliary cannulation.
A high affinity (1-2 nM) radioiodinated, photoaffinity probe for the dopamine transporter, 1-(2-[bis-(4-fluorophenyl)-methoxylethyl)-4-(2-[4-azido-3- [125I]iodophenyl]ethyl)piperazine ([125I]FAPP) has been synthesized. Upon photolysis, [125I]FAPP incorporates into a striatal polypeptide of apparent Mr 62,000 as visualized by autoradiography following sodium dodecyl sulfate-PAGE. Photoincorporation of [125I]FAPP into the Mr 62,000 polypeptide was stereoselectively inhibited by various dopamine uptake agents with a potency order typical of the dopamine transporter. The glycoprotein nature of the apparent Mr 62,000 polypeptide was assessed following specific exo- and endoglycosidase treatment. The dopamine transporter appears to be associated with complex-type oligosaccharides as indexed by its susceptibility to neuraminidase but not alpha-mannosidase digestion. Complete N-linked deglycosylation of the neuronal dopamine transporter with the endoglycosidase, glycopeptidase-F, increased the electrophoretic mobility of the 62 kDa polypeptide to apparent Mr 48,000. [125I]FAPP should prove to be a useful probe for the molecular characterization of the dopamine uptake site in various tissues and under certain pathophysiological states.
The dopamine D1 receptor was identified in the calf parathyroid gland. The binding of the selective D1 receptor antagonist [3H]SCH-23390 to membranes of calf parathyroid was specific, reversible, and saturable with a dissociation constant of approximately 200 pM and a receptor density of 30 fmol/mg of protein. Dopaminergic agonists and antagonists inhibited [3H]SCH-23390 binding in a concentration-dependent and stereoselective manner with an appropriate pharmacological specificity for D1 dopamine receptors. Moreover, potent dopaminergic agonists recognized two affinity forms of the receptor, one displaying high affinity for agonists, termed D1 High, and one with low affinity, D1 Low. The addition of the nonhydrolyzable guanine nucleotide guanyl 5'-yl-imidodiphosphate caused the complete transition of the agonist high affinity form (D1 High) of the receptor to one displaying only low affinity for agonists (D1 Low). Sodium ions, however, caused a approximately 5-fold decrease in the affinity of agonists at both D1 High and D1 Low. Virtually identical results were obtained on D1 receptor preparations of neural origin. The D1 receptor identified here appears to be the one responsible for the physiological effects on the parathyroid gland, because dopamine-stimulated cAMP accumulation is stereoselectively blocked by the D1 receptor antagonist SCH-23390 in dispersed cells of the parathyroid gland. Moreover, a series of nine dopaminergic antagonists and agonists shows an excellent correlation between their potency in [3H]SCH-23390 binding assays and their corresponding effects on cAMP accumulation. In the case of agonists, Ka for activation of cAMP accumulation agrees most closely with the agonist low affinity site in binding experiments. Specific [3H]spiperone binding to D2 dopamine receptors was not detected in this tissue and as such, the calf-parathyroid gland provides a model system in which to study the molecular characteristics of dopamine D1 receptor-mediated events.