Long-term follow-up of thoracoscopic splanchnicectomy for chronic pancreatitis pain.

BACKGROUND: Thoracoscopic splanchnicectomy (SPL) has been reported to give excellent short-term pain relief in chronic pancreatitis. This study prospectively evaluates the long-term efficacy of SPL in pancreatitis patients. METHODS: Chronic pancreatitis patients with severe pain unrelieved by standard therapy completed a standard 10-point analogue pain scale prior to surgery and at postoperative visits. Midline and left-sided pain was treated with left SPL; right-sided pain was treated with right SPL. If pain recurred on the contralateral side, contralateral SPL was done. RESULTS: Fifteen patients underwent SPL. Eleven of them required narcotics preoperatively. Follow-up is complete and ranges from 4.2 to 6.1 years (median, 5.75). All patients had constant pain prior to surgery. Following SPL, it decreased in the short term to a mean of 3.9 attacks a month. At long-term follow-up, the mean number of attacks was 8.6 per month. Preoperatively, the mean score for worst pain within the last 2 months was 9.1. This score decreased to 3.9, but at long-term follow-up it had increased to near preoperative values (8.6). Current severity of pain decreased from 7.2 preoperatively to 2.9 at short-term follow-up, but at long-term follow-up it had increased. The degree of disability decreased from 9.1 preoperatively to 5.1 at short-term follow-up, but in the long term it increased toward preoperative values. Although eight patients were narcotic free at early follow-up, only three remained narcotic free in the long-term. CONCLUSION: Thoracoscopic SPL offers short-term relief of pain from chronic pancreatitis, but the relief is not durable in most cases. Similarly, there are short-term improvements in degree of disability, mood, and freedom from narcotic use that are not sustained in the long-term. Nevertheless, two-thirds of patients stated that they would have the surgery again.

Celiac disease and recurrent pancreatitis.

BACKGROUND: Celiac disease is associated with pancreatico-biliary disease. Postulated mechanisms include reduced gallbladder emptying due to impaired cholecystokinin release and pancreatitis due to malnutrition. We hypothesize that celiac disease may also be associated with pancreatico-biliary abnormalities due to duodenal inflammation and papillary stenosis. METHODS: Over a 48-month period, 169 patients referred for possible sphincter of Oddi dysfunction who underwent pancreatico-biliary manometry were tested for gliadin and endomysial antibodies. Duodenal and papillary biopsies were preformed in those patients who were positive. RESULTS: Celiac disease was diagnosed in 12 (7.1%; 3 men, 9 women). The mean age was 61 years as compared with 37 years for those patients without celiac disease. All of the celiac patients had been referred for recurrent abdominal pain and/or idiopathic pancreatitis. Ten had idiopathic recurrent pancreatitis with elevated amylase and lipase levels. Two of these patients also had mildly elevated liver function tests associated with the abdominal pain. Only 3 of 12 patients had a prior diagnosis of celiac disease. These 12 patients had manometric evidence of stenosis and histologic evidence of periampullary inflammation as well as histologic changes consistent with celiac disease. In 10 of 12 patients sphincterotomy or extension of a prior papillotomy was performed. Two patients were treated with a gluten-free diet alone. CONCLUSIONS: We describe 12 patients with papillary stenosis and celiac disease. In 9 cases the celiac disease was a new diagnosis. Celiac disease should be considered in the etiology of papillary stenosis or idiopathic recurrent pancreatitis.

University of Iowa Hospital and Clinics: outcomes management.

Delivery of quality patient care and management of patient outcomes is critical to the success of academic medical centers in the ever-changing health care market. The University of Iowa Hospitals and Clinics (UIHC) promotes quality care through the provision of organizational structures and processes that are described in this article. In addition, quality of care and outcomes management are described by members in various roles within the UIHC health care system. It is the authors' belief that understanding quality from these various perspectives helps UIHC work across departments to achieve excellence in patient care.

A percutaneous biopsy technique for patients with suspected biliary or pancreatic cancer without a radiographic mass.

BACKGROUND: Treatment of malignant pancreatic and/or biliary strictures requires tissue diagnosis. Since cytologic brushings at endoscopic retrograde cholangiopancreatography (ERCP) of these strictures has a poor sensitivity for malignancy (30-83%) (see ME Ryan. Gastrointestinal Endoscopy 1991;37(2):139-143; and MB Cohen, Wittchow RJ, Johlin FC, et al. Mod Pathol 1995;8:498-502), tissue diagnosis must be obtained by another route. We report our experience of percutaneous biopsy of malignant pancreatic and/or biliary strictures even when no radiographic mass is present. METHODS: At ERCP, five patients demonstrated pancreatic and/or biliary duct strictures, had atypical cytological brushings, and had their strictures stented. No mass to account for the strictures could be identified on CT. These five patients underwent percutaneous biopsy of the persistent material by CT within 10 days of the ERCP. RESULTS: Two patients had adenocarcinoma of the pancreas. One patient had malignant lymphoma and another had cholangiocarcinoma. One patient had inflammatory cells and was followed. CONCLUSIONS: If the diagnosis of malignancy cannot be made at the time of the ERCP sampling, then our experience suggests that a percutaneous biopsy should be performed even if a mass is not present using the stent as a target.

Thoracoscopic splanchnicectomy for chronic pancreatitis pain.

BACKGROUND: The study was undertaken to quantitate the effects of thoracoscopic splanchnic nerve resection (SPL) on pain from chronic pancreatitis. METHODS: Patients with chronic pancreatitis pain completed an analog pain scale before operation and at postoperative visits. Midepigastric and left-sided pain was treated with left SPL; right-sided pain was treated with right-sided SPL. If pain recurred on the contralateral side, the patient underwent contralateral SPL. RESULTS: Fifteen patients underwent SPL. Eleven patients required daily narcotics for relief of pain before operation. Eight patients had unilateral SPL, whereas seven ultimately had a bilateral operation (median follow-up, 18 months). Fourteen patients had constant pain before operation, which decreased to a mean of 2.8 attacks per month (p < 0.0001). Before operation, the "worst pain within last two months" was 9.1 on pain scale (range, 0 for no pain, to 11 for constant pain). After operation this decreased to 5.1 (p < 0.002). "Current severity" of pain decreased from 6.5 before operation to 2.0 after operation (p < 0.0005). The "amount pain is interfering with daily activities" decreased from 7.3 before operation to 2.3 after operation (p < 0.0001). Seven patients (46%) no longer require narcotics and are classified as having had good results. Five patients (33%) are classified as improved and have had a major reduction in narcotic needs. Three have had no significant pain relief and are classified as having had poor results. CONCLUSIONS: Thoracoscopic SPL offers substantial promise in the therapy of pain from chronic pancreatitis.

Brush cytology of the extrahepatic biliary tract: comparison of cytologic features of adenocarcinoma and benign biliary strictures.

Malignant strictures of the extrahepatic biliary tract are difficult to discern from benign strictures solely by clinical and/or radiographic findings. Endoscopic retrograde wire-guided brushings of strictures have proven to be useful in evaluating such lesions. Because the reported sensitivity of diagnosing adenocarcinoma of the extrahepatic biliary tract by this technique has varied considerably (44 to 100%), we undertook a retrospective study to determine if the diagnostic accuracy could be increased by identifying key cytologic features by reviewing a series of 90 biliary tract brushings from 80 patients. The cytologic diagnosis was confirmed either by additional pathologic material and/or clinical follow-up. Utilizing a multiple logistic regression analysis, three key cytologic features were identified that were useful in separating benign from malignant strictures; these features included: nuclear molding, chromatin clumping, and increased nuclear-cytoplasmic ratio. The presence of two of these three features resulted in a sensitivity of 83%; the corresponding specificity was 98%. The use of these key features should aid the cytologist in better recognizing malignant cells in biliary tract brushings.

Generation of a human monoclonal antibody to hepatitis C virus, JRA1 by activation of peripheral blood lymphocytes and hypo-osmolar electrofusion.

We have generated a human monoclonal antibody with binding specificity for hepatitis C virus (HCV)-specific peptides using peripheral blood lymphocytes isolated from a HCV antibody positive patient. The B-lymphocytes were stimulated with lipopolysaccharide (LPS) for 72 hours prior to the fusion. A recently described high efficiency hypo-osmolar electrofusion technique was employed, allowing generation of a large number of human hybridomas. The hybridomas were screened for human immunoglobulin and HCV-specific peptide binding by EIA. A single HCV-positive clone, JRA1, was detected and sub-cloned. Isotype analysis showed it to secrete an IgM lambda monoclonal antibody. The antibody was positive on both first and second generation HCV antibody analysis. This study confirms that viable pathogen-specific B-cells may be recovered from the peripheral blood. Although such cells are likely to be relatively uncommon in the circulating B-cell pool, they may be successfully immortalized by high efficiency electrofusion techniques. This technique might be valuable for the generation of human monoclonal antibodies with specificity for other human pathogens.

Intestinal dysmotility in patients with sphincter of Oddi dysfunction. A reason for failed response to sphincterotomy.

Sphincter of Oddi dysfunction (SOD) is associated with abdominal pain and is treated by sphincterotomy. Of 215 patients who underwent biliary sphincterotomy for SOD in our institution, 26 reported no improvement and 25 of those were found to have pancreatic sphincter dysfunction and subsequently underwent pancreatic septotomy. Nine patients remained symptomatic after the second intervention. Six of those nine patients, and seven of the 16 patients who improved after the septotomy, agreed to undergo an ambulatory duodenojejunal (DJ) manometry. DJ manometry was abnormal in four of the six symptomatic patients but only in one of seven patients who became asymptomatic after endoscopic treatment. We conclude that the persistence of symptoms after endoscopic ablation of the biliary and pancreatic sphincters is associated with abnormal intestinal motility, which may explain in part the lack of response to the endoscopic treatment.

Atheromatous embolization resulting in acute pancreatitis after cardiac catheterization and angiographic studies.

Acute pancreatitis has a spectrum from mild disease to severe organ destruction resulting in multiple system organ failure. In this study, we report data from 21,680 discharge summaries during a 10-year period of patients who had undergone transabdominal angiographic procedures in whom the diagnosis of pancreatitis was noted in the discharge coding. We detected 39 patients in whom pancreatitis was coded during the same hospitalization, but only nine patients had no other risk factors for pancreatitis other than the temporal relation with the angiographic procedure. Three of these nine patients died of complications caused by pancreatitis. All of the patients with poor outcomes in this report fulfilled more than three Ranson criteria within 48 hours of the original angiographic procedure. Abdominal imaging with ultrasound or computed tomography was abnormal in all the patients who fulfilled more than three Ranson criteria. The histology from the surgical procedures or the autopsies performed on the three patients who died showed extensive cholesterol embolization primarily to the visceral organs. Extensive pancreatic necrosis was evident in these patients. We conclude that acute pancreatitis after transabdominal angiographic procedures is a rare but a potential fatal event. The prognosis from this event is partially predicted by the Ranson criteria that are evident within the first 48 hours.

Sphincter of Oddi dysfunction following liver transplantation. Screening by bedside manometry and definitive manometric evaluation.

Although sphincter of Oddi dysfunction (SOD) has been extensively studied in the nontransplant setting, the diagnostic criteria after liver transplantation are not well defined and have been based on clinical features without manometric documentation. The purpose of this study was twofold: (1) to determine the manometric patterns associated with SOD following orthotopic liver transplantation (OLT) and (2) to define the usefulness of bedside T-tube manometry as a screening tool for SOD. ERCP with simultaneous manometry of the sphincter of Oddi (SO) was performed in five patients following OLT with choledochocholedochostomy (CDCD) between 1990 and 1992. The diagnosis of SOD was suspected based on persistently elevated liver function tests, distal common bile duct dilatation in the absence of strictures, and an elevated resting bile duct pressure as measured by bedside T-tube manometry. Two different manometric patterns of SOD were observed. The first pattern (N = 4) consisted of elevated SO basal pressures, infrequent simultaneous phasic activity, and an abnormal response to cholecystokinin-octapeptide (CCK-OP). The second pattern (N = 1) consisted of low basal pressures and absent phasic activity. Four patients were successfully treated with papillotomy and stenting, while the fifth patient required conversion to a choledochojejunostomy because of a concomitant anastomotic stricture. The abnormal SO manometric profiles in patients suspected of having SOD after OLT were different from those observed in the nontransplant setting. Bedside T-tube manometry allowed measurement of the resting bile duct pressure and may be a useful screening tool for SOD.

Drainage of the gallbladder in patients with acute acalculous cholecystitis by transpapillary endoscopic cholecystotomy.

The mortality associated with acute acalculous cholecystitis approaches 50%. Removal or decompression of the gallbladder in these patients may prevent gallbladder rupture and may be lifesaving. This is usually accomplished by cholecystectomy, cholecystotomy, or percutaneous gallbladder drainage. We describe a novel transpapillary endoscopic approach to gallbladder drainage in patients at high surgical risk. A total of seven high surgical risk patients were treated with transpapillary endoscopic cholecystotomy. Cannulation of the cystic duct was accomplished by using standard hourglass-tipped catheters in two patients. A new "selector" catheter was developed for selective cannulation of the cystic duct and used in the other five patients. Five of the seven patients showed evidence of clinical, radiographic, and laboratory improvement after treatment. We conclude that transpapillary endoscopic cholecystotomy may be an effective treatment alternative for high surgical risk patients with acalculous cholecystitis.

Omeprazole heals mucosal ulcers associated with endoscopic injection sclerotherapy.

Endoscopic injection sclerotherapy (EIS) is a standard and definitive therapy for bleeding esophageal varices. While the overall complication rate of the procedure is low, a substantial minority of patients treated by EIS develop refractory mucosal ulceration and/or esophageal strictures. However, despite the prophylactic use of H2 blockers and sucralfate in our EIS protocol, we observed a number of patients who developed nonhealing esophageal and/or gastroduodenal ulceration. We conducted an open trial in which we enrolled nine patients who had refractory ulcer disease. Patients that enrolled in the trial exhibited complete healing of their mucosal ulcers. These results suggest that acid is an important contributory factor in the pathogenesis and perpetuation of EIS-associated mucosal ulceration. Patients with alcohol-associated liver disease may be at increased risk for the development of EIS-associated complications.

Sphingomyelin content of intestinal cell membranes regulates cholesterol absorption. Evidence for pancreatic and intestinal cell sphingomyelinase activity.

Micellar cholesterol uptake and secretion were investigated in the human intestinal cell line CaCo-2 following depletion of apical membrane sphingomyelin. The addition of exogenous sphingomyelinase, which hydrolysed 60% of prelabelled sphingomyelin, resulted in a 50% decrease in the uptake of cholesterol from bile salt micelles. The flux of membrane cholesterol into the cell by the hydrolysis of membrane sphingomyelin decreased the rate of cholesterol synthesis by 43% and inhibited hydroxymethylglutaryl-CoA reductase activity by 54%. Moreover, the rate of cholesterol esterification was increased 4-fold. Total cellular cholesterol mass was unchanged by the addition of sphingomyelinase; however, cholesteryl esters increased by 50% and the amount of unesterified cholesterol decreased significantly. The basolateral secretion of cholesterol mass was also decreased following sphingomyelin hydrolysis. Human pancreatic juice was found to contain neutral sphingomyelinase activity which required taurocholate for full expression. The presence of neutral sphingomyelinase activity was also documented in membranes prepared from CaCo-2 cells and in whole homogenates from human duodenal biopsies. The data suggest that the amount of sphingomyelin present in the apical membrane of the intestinal absorptive cell regulates cholesterol uptake from bile salt micelles. Sphingomyelinase activity within intestinal cells and in pancreatic juice could alter the sphingomyelin content of brush-border membranes of small intestinal absorptive cells and thus regulate the amount of cholesterol absorbed by the gut.

The effect of guidewires during electrosurgical sphincterotomy.

We describe six electrosurgical incidents and one complication which occurred during guidewire-assisted sphincterotomy. Studies were conducted on three types of guidewires: Teflon painted, Teflon sheathed, and polymer coated. Scanning electron micrographs demonstrated surface imperfections in the painted Teflon guidewire coating, which allowed for potential electrical short circuits between cutting wire and guidewire through a septal defect in a double channel catheter. Septal defects were found in 25% (1 of the 4 tested) of the factory fresh sphincterotomes that were used in this study, and in 10% (6 of 57) of those used clinically. Induced current (capacitively coupled) present on the guidewires was measured at 13 to 30 mA for typical sphincterotomy settings. The induced current on sheathed guidewires, without any insulation defects, was measured at less than 1 mA at typical operating powers. As both short circuits and induced currents place the patient at risk for burns or perforation at the distal end of the guidewire, we suggest the use of a Teflon-sheathed rather than Teflon-painted guidewire, if the wire is to be left in place during sphincterotomy. The Teflon sheath offers the thickest insulation, a very low probability of surface defects, and therefore a high index of safety.

The pathophysiology, evaluation and management of motility disorders of the biliary tract.

Significant advances in the understanding of biliary tract physiology have occurred during the past 20 years. Through careful studies in animals, the fluid mechanics and normal regulatory mechanisms involved in sphincter of Oddi function have been partially elucidated. Many of the basic concepts have been validated in human studies by newly developed testing methods. Endoscopic retrograde cholangiopancreatography is crucial in demonstrating both normal anatomy and mechanical or structural abnormalities of the duct system. Fat-meal--or CCK-stimulated ultrasonography and quantitative hepatobiliary scintigraphy offer reliable and noninvasive screening methods to evaluate patients with suspected sphincter of Oddi dysfunction. Biliary manometry is key in defining normal and abnormal motility patterns of the sphincter of Oddi region. The existence of the problem is being solidly established, but the optimal therapy is still somewhat unclear. The use of endoscopic balloon dilatation is not encouraging; drug therapy holds promise, but must be subjected to careful clinical trials. Sphincter surgery is fading from use and is being replaced by endoscopic sphincterotomy. Unfortunately the long-term results of sphincterotomy and the overall safety of the procedure are not known. Biliary motility problems do exist, but both diagnostic studies and therapeutic maneuvers require judgement and skill in their application. Use of potentially harmful treatments must be employed only after careful and thorough testing.

Studies on the mechanism of methanol poisoning: purification and comparison of rat and human liver 10-formyltetrahydrofolate dehydrogenase.

Methanol poisoning in primates and humans is due to formate accumulation as a result of low rates of formate oxidation. This toxicity is not seen in rats, where formate oxidation rates are high. Formate oxidation in vivo is dependent on hepatic tetrahydrofolate levels and on the activity of the enzyme 10-formyl-tetrahydrofolate (10-formyl-H4folate) dehydrogenase (EC 1.5.1.6). Because hepatic 10-formyl-H4folate dehydrogenase activity is lower in human liver than in rat liver, studies were performed investigating the properties of this enzyme in rat and human liver. 10-Formyl-H4folate dehydrogenase was purified to homogeneity from rat and human liver and was found to possess similar subunit molecular weights on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (96,000). N-Terminal amino acid analysis of the pure proteins showed an identical sequence for the first 16 amino acids. Antibodies raised in rabbits against the rat liver enzyme were inhibitory toward the activity of both rat and human liver enzymes and appeared to recognize only the 10-formyl-H4folate dehydrogenase in cytosolic preparations of rat and human liver. Immunoblots of pure rat and human liver 10-formyl-H4folate dehydrogenase showed similar staining intensity. It is concluded that rat and human liver 10-formyl-H4folate dehydrogenase possess very similar properties and that the activity of the enzyme in human liver is lower than that of rat liver, due to a reduced amount of enzyme protein in human liver. This may be an important factor in regulating formate oxidation in humans and may explain, in part, the accumulation of formate and the mechanism of toxicity of methanol in humans.

Electrohydraulic shock wave lithotripsy (ESWL) fragmentation of retained common duct stones.

Retained or recurrent stones in the common bile duct remain a clinical problem in 2% to 5% of patients undergoing cholecystectomy. Nonoperative extraction via the T tube tract or endoscopic sphincterotomy is successful in 85% to 95% of patients; however, the remainder require reoperation. This study evaluates the efficacy of electrohydraulic shock wave lithotripsy therapy of common duct stones too large to be extracted endoscopically or by T tube. Six patients were entered into the study. Ages ranged from 62 to 93 years. All patients either had severe preexisting systemic disorders or were of an advanced age. Stones ranged in size from 10 to 41 mm, with a mean largest dimension of 22 mm. In all patients either extraction by traditional nonoperative means failed or there was a stone that was considered to be too large to be extracted successfully. Patients were treated with 1200 to 2400 shocks at 16 to 20 kV. Five of six patients were treated with local anesthesia and sedation. Stones were successfully fragmented in all but one patient. Five patients required extraction of the remaining fragments either through the T tube tract (one patient) or via endoscopic sphincterotomy. All patients were free of stones at discharge, with the exception of one patient with severe cirrhosis who had an intrahepatic stone behind a right hepatic duct stricture. This stone had been successfully fragmented but an endoscopic retrograde cholangio-pancreatogram revealed some residual fragments despite normal alkaline phosphatase and bilirubin values. There were no hospital deaths, although the patient with the intrahepatic stone died of bleeding varices several months later. Electrohydraulic shock wave lithotripsy seems to be an effective adjuvant treatment in clearing the bile duct of stones that would otherwise require reoperation.