Allan G. Halline

The role of endoscopic retrograde cholangiopancreatography in acute and chronic pancreatitis.

Endoscopic retrograde cholangiopancreatography (ERCP) plays a pivotal role in the management of patients with acute and chronic pancreatitis. Whereas endoscopic observation during ERCP permits recognition of abnormalities involving the major and minor duodenal papillae such as papillary tumors or choledochocele, radiographic evaluation enables the detection of structural abnormalities of pancreaticobiliary ducts like strictures or calculi. Sphincter of Oddi manometry, a technical advance of ERCP, is essential for the diagnosis of sphincter of Oddi dysfunction, which may present clinically as recurrent pancreatitis. Because structural alterations of the pancreatic duct forms the hallmark of chronic pancreatitis, ERCP is highly sensitive and specific in diagnosing chronic pancreatitis. Apart from its diagnostic role, ERCP offers a variety of possibilities for therapeutic interventions in selected problems associated with pancreatitis. Endoscopic papillectomy and mucosal resection for tumors of the papilla, unroofing of a choledochocele, and sphincterotomy for sphincter ablation in sphincter of Oddi dysfunction are some of the therapeutic interventions possible during ERCP. Pancreatic ductal hypertension, which is considered to be the major pathophysiologic mechanism for disabling abdominal pain in chronic pancreatitis, also can be managed by ERCP-directed treatments. Pancreatic sphincterotomy, dilation of strictures, lithotripsy, extraction of calculi, and deployment of endoprosthesis constitute the commonly used therapeutic techniques in this situation. Besides offering a noninvasive alternative, these treatments are associated with a favorable clinical outcome comparable with that of operative treatments. Nevertheless, complications such as acute pancreatitis, bleeding, perforation, or sepsis may occur in 5% to 10% of patients undergoing these procedures. Therefore, careful selection of patients, appropriate preoperative care, and a team approach, including surgeon, interventional radiologist, and endoscopist, are important.

The role of pancreatoscopy in the preoperative evaluation of intraductal papillary mucinous tumor of the pancreas.

Background Intraductal papillary mucinous tumor of the pancreas is a rare neoplasm managed by operative resection of the affected segment of the pancreas. Goals To evaluate the role of peroral pancreatoscopy in the diagnosis and preoperative localization of the affected region of the pancreatic duct and to undertake the appropriate operation for each patient. Study Five patients with suspected intraductal papillary mucinous tumor of the pancreas were studied using endoscopic retrograde cholangiopancreatography, computed tomography of the abdomen, endoscopic ultrasonography, and peroral pancreatoscopy. The findings from these studies were compared, and operative resection was performed in each patient based on pancreatoscopic findings. Results Of the five patients with suspected intraductal papillary mucinous tumor, only four had histologically confirmed tumor, and the remaining one patient had a retention cyst of the pancreas. Pancreatoscopy correctly identified all four patients with the tumor while excluding the diagnosis of papillary tumor in one. Conclusion Peroral pancreatoscopy is valuable in the preoperative evaluation of intraductal papillary mucinous tumor of the pancreas, especially in the localization of such tumor.

Acute acid exposure increases rabbit esophageal cell proliferation

In the present study we examined whether an acute infusion of HCl into the esophagus of rabbits would cause an increase in esophageal cellular proliferation independent of morphologic evidence of cell injury. To examine this question, the distal two thirds of the rabbit esophagus was infused for 1 hour with either 40 mmol/L HCl or NSS (control), and cellular proliferation was studied 24 and 48 hours later by using bromodeoxyuridine (BrDu) to label the nuclei of dividing cells and ornithine decarboxylase (ODC) enzyme activity as a biochemical index of cell division. Although there was no gross or microscopic evidence of cell necrosis or mucosal inflammation 24 hours after H+ infusion, BrDu labeling of basal cell nuclei was significantly greater 24 hours after H+ infusion (31%+/-6%) as compared with that in control animals infused with NSS (15%+/-4%). This increase in labeling index was paralleled by a threefold greater ODC enzyme activity at 24 hours with H+ infusion. Rete pegs were infrequent in control tissues (4+/-4 rete pegs per 100 microm of esophageal length) or in animals examined 24 hours after acid exposure (4+/-2 rete pegs per 100 microm). However, rete pegs were very prominent 48 hours after acid infusion (22+/-6 rete pegs per 100 microm). A short exposure to acid can cause a significant increase in mucosal proliferation independent of injury, suggesting that esophageal cell acidification either directly or indirectly acts as a tissue mitogen.

Urinary N1-Acetylspermidine and N8-acetylspermidine excretion in normal humans and in patients with colorectal cancer

UrinaryN1-acetylspermidine (N1SPD) andN8-acetylspermidine (N8SPD) were measured in 24-hr urine specimens from 42 patients with colon adenocarcinoma and 29 healthy controls to assess their use as markers for colon cancer screening. Serial spot urines in four controls demonstrated significant fluctuations in these polyamine levels throughout the day without a distinct circadian pattern and therefore all subsequent analyses were performed on 24-hr collections. Both N1SPD and N8SPD were significantly increased in colon cancer patients compared to controls. Neither test correlated with tumor stage or location, but N8SPD was elevated in patients with poorly differentiated adenocarcinoma when compared to moderate or well-differentiated tumors. Using receiver operator characteristic (ROC) analysis, N1SPD had a higher information content than N8SPD, N1SPD+N8SPD, or the ratio of N1SPD/N8SPD and at a normal cut-off value of 4.0 nmol/mg creatinine, yielded a 95% specificity and 50% sensitivity for colon cancer.

A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity

BACKGROUND: Carrageenan is a very common food additive in Western diets, but predictably causes inflammation in thousands of cell-based and animal experiments. OBJECTIVE: To assess the impact of carrageenan exposure on the interval to relapse in patients with ulcerative colitis in remission. METHODS: A randomized, double-blind, placebo-controlled, multicenter, clinical trial was conducted to assess if patients with ulcerative colitis in remission would have a longer interval to relapse if they followed a diet with no carrageenan. All participants were instructed in the no-carrageenan diet and were randomized to either placebo capsules or carrageenan-containing capsules. The carrageenan in the capsules was less than the average daily carrageenan intake from the diet. Relapse was defined as an increase of two or more points on the Simple Clinical Colitis Activity Index (SCCAI) and intensification of treatment for ulcerative colitis. Participants were followed by telephone calls every two weeks until relapse or one year of participation. The occurrence of relapse and inflammatory biomarkers were compared between the two groups. RESULTS: Twelve patients completed study questionnaires. Three patients who received carrageenan-containing capsules relapsed, and none of the patients who received placebo-containing capsules relapsed (p = 0.046, log-rank test). Laboratory tests showed increases in Interleukin-6 (p = 0.02, paired t-test, two-tailed) and fecal calprotectin (p = 0.06; paired t-test, two-tailed) between the beginning and the end of study participation in the carrageenan-exposed group, but not in the placebo-group. CONCLUSION: Carrageenan intake contributed to earlier relapse in patients with ulcerative colitis in remission. Restriction of dietary carrageenan may benefit patients with ulcerative colitis.

Urinary organ specific neoantigen - A potentially diagnostic test for colorectal cancer

Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A405:0.717±0.500) vs 27 controls [0.121 ±0.273 (P<0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N=13), adenomas (N=26), inflammatory bowel disease (N=8), or having a normal colonoscopic examination (N=24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P<0.05). The presence of the Mr 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.

EUS: An Ideal Initial Test for Elderly Patients with Idiopathic Pancreatitis

Methods: We reviewed 67 cases of patients who underwent cholecystectomies and who also showed thickened gallbladder wall in their preoperative EUS. According to the post-surgical pathologic diagnosis, the cases were classified into malignant and benign diseases, and then they were statistically compared with several findings of EUS of thickened gallbladder wall such as thickness, extent of wall thickening, associations of gallstones, loss or preservation of layered structure of wall, internal echo pattern within thickened wall, associations of microcyst or echogenic nodule within thickened wall, and irregularity of inner surface of thickened wall. Results: Pathologic diagnoses included 10 cancers and 57 benign gallbladder diseases. The sensitivity and specificity of EUS examination for diagnosis of the gallbladder cancer were 90% and 98% respectively, and especially in the specificity, EUS was superior to that of abdominal ultrasonography or abdominal CT scan that were also performed to enrolled patients preoperatively. Through statistical analyses, EUS findings of thickened wall such as thickness, associations of gallstones, loss or preservation of layered structure, and irregularity of inner surface of thickened wall were turned out to be the statistically significant variables in the differential diagnosis between malignant and benign causes of thickened gallbladder wall. On the multivariate analyses, loss or preservation of layered structure, and irregularity of inner surface of thickened wall were finally remained as independent variables, odds ratio (OR) 12.10: 95% CI (1.2, 137.6), OR 15.80: 95% CI (1.5, 167.0). Conclusion: EUS is useful to diagnose gallbladder cancer when gallbladder shows thickened wall and EUS findings of thicker wall, absence of gall stones, loss of normal layered structure, and irregular internal surface of thickened wall are predictive factor of gallbladder cancer. *T1603 EUS: An Ideal Initial Test for Elderly Patients with Idiopathic Pancreatitis Karin M. Rettig, Allan G. Halline, Russell D. Brown, Rama P. Venu Background: Current standard of care for patients with idiopathic pancreatitis (IP) involves an extensive evaluation including ERCP with possible sphincter manometry to identify an etiology. ERCP carries a significant risk of pancreatitis in comparison to endoscopic ultrasound (EUS). Furthermore, EUS identifies malignancy, stones, sludge, and chronic pancreatitis as well as or better than ERCP. Older patients may have a higher risk of malignancy and a lower incidence of sphincter dysfunction (SD), making EUS an attractive method for initial endoscopic evaluation in this group. Aim: To determine if EUS should be used as the initial investigation of choice in older patients with IP. Methods: Patients >55 years old referred with IP were evaluated with history, physical, amylase, lipase, triglyceride, calcium, liver enzymes, ultrasound and CT. Patients in whom the etiology was unknown after noninvasive evaluation were included in this study. Each patient had EUS, followed by helical CT and ERCP +/sphincterotomy (ES). Radial array EUS was done first followed by linear array EUS with possible fine needle aspirate (FNA). CT, ERCP with brush cytology and/or SOM was performed in all patients. ES, stone extraction, stent placement, laparotomy, or Whipple operation was done based on ERCP results. Results: Of 20 patients, an etiology was identified in 7 (35%). Four of 20 patients had a malignancy (3 pancreas, 1 periampullary). One patient each had choledocholithiasis, pancreas divisum, SD, and early chronic pancreatitis. EUS demonstrated a mass in all 4 patients withmalignancy, andFNAof eachmasswas positive for adenocarcinoma in 3. ERCP showed PD stricture suggestive ofmalignancy in 3 patients, with brush cytology positive for adenocarcinoma in one. Both EUS and ERCP identified a common bile duct stone in one patient, while SD (1) and pancreas divisum (1) were diagnosed exclusively by ERCP. EUS established a diagnosis in 6/7 (84%), while ERCP did so in 4/7 (56%). CT scanning revealed a mass in only one of four cancer patients and an enlarged pancreas due to pancreatitis in 17/20 patients. Three of four patients with cancer underwent Whipple surgery, and all three were correctly staged by EUS. One patient had metastasis to the liver and was treated with endoprosthesis. Conclusion: EUS should be considered as the initial endoscopic study of choice in older patients with IP. EUS has an overall higher yield and can accurately establish a tissue diagnosis, enable staging of malignancy, and aid in appropriate planning for therapy.

7164 Endoscopic sphincterotomy is safe and well tolerated in orthotopic liver transplantation (olt) patients.

Introduction Biliary complications such as bile leak (BL) and anastomotic strictures (AS) occurs in 15-20% of patients undergoing orthotopic liver transplant(OLT), and can be treated successfully by endoscopic techniques of stent placement and dilation, respectively. Endoscopic sphincterotomy (ES) is commonly performed during therapeutic endoscopic retrograde cholangiopancreatography (ERCP) to facilitate repeated cannulation and stent placement. Given concerns for bacterial contamination and stasis at the anastomotic site, some endoscopists avoid ES in these immunocompromised patients. Aim To determine the safety and clinical outcome of ES in OLT patients(“ES Group”) and to compare their course to OLT patients who underwent ERCP without ES (“No ES Group”) Methods Patients who received OLT between 1994-98 and required ERCP were included in the study. Patient demographics, ERCP indications, complications and post- ERCP course were analyzed. Complications of ERCP were catagorized as procedure-related and delayed(=30 days). Late adverse events recorded were related to biliary tract disease. Results Twenty-seven post OLT patients(17M, 10F, mean age 49 yrs, range 31-68) who required ERCP were studied. Mean follow up was 30 mos. in the ES group, and 35 mos. in the No ES group. ERCP indications, complications and clinical course are noted in the table below. Most (14/15) patients in the ES group underwent multiple ERCPs with stents and dilation for AS as per our protocol. Delayed ERCP complications occurred in 3 of 15 in the ES group(20%); all 3 had stones or sludge which predated ERCP/ES. The 3 patients who suffered late adverse events had recurrence of AS without new stones or sludge. No deaths were attributable to ES. Conclusion Endoscopic sphincterotomy in orthotopic liver transplant patients undergoing ERCP is safe, with a complication rate comparable to published data for non-OLT patients. Delayed complications and late adverse events (Stent occlusion, restenosis, death) in these patients appear to be unrelated to sphincterotomy per se, but common to all OLT patients.