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Biomedical subjects

K D Lillemoe

Publications and source records attributed to K D Lillemoe.

At least 19 recordsLinked to original sources

Patients with uncomplicated cholelithiasis acidify bile normally.

Reports have suggested that patients with gallstones have gallbladder bile that is less acidic and more saturated with calcium carbonate than patients without gallstones. This failure to acidify bile may play a role in the formation of gallstones. We, therefore, compared gallbladder bile pH, ionized calcium, and calcium carbonate saturation index from patients undergoing either incidental gallbladder removal (controls, n = 23) or elective cholecystectomy for gallstones (n = 55). Gallstones were classified as either cholesterol (n = 39) or black pigment (n = 16) stones. No difference in gallbladder bile pH was noted among the controls, cholesterol stone, and pigment stone patients. In addition, no difference in ionized calcium concentration or CCSI was noted among the three groups. The pH in additional patients (n = 49) with acute cholecystitis, common bile duct obstruction, biliary tract infection, and cystic duct obstruction was significantly more acidic. We conclude that neither a defect in bile acidification nor increased saturation of calcium carbonate explains why human cholesterol or pigment gallstones form.

Adult

Effect of cholecystectomy on gallbladder bile composition.

Human bile samples are commonly used in biliary research; however, the optimal sampling technique is not known. The current study examines whether bile obtained prior to operative manipulation of the gallbladder differs in composition from samples obtained after cholecystectomy. Gallbladder bile samples were obtained from 26 patients undergoing cholecystectomy. An initial sample was obtained prior to manipulation or devascularization of the gallbladder, and a second sample was obtained after the removal of the gallbladder from the operative field. Gallbladder bile pH and total protein were significantly increased in the postcholecystectomy samples. Bile obtained after cholecystectomy also contained significantly less phospholipid. Gallbladder bile cholesterol, total bile acids, bilirubin, ionized and total calcium, cholesterol saturation index, and total lipids were similar between techniques. These results indicate that manipulation of the gallbladder during cholecystectomy produces alterations in gallbladder bile composition. These results also emphasize the need for consistent sampling technique when obtaining samples for biliary research.

Bile

Selective cholangiography. Current role in laparoscopic cholecystectomy.

The initial 22-month experience with laparoscopic cholecystectomy in 400 patients employing an algorithm of selective cholangiographic evaluation is reported. Preoperative or postoperative endoscopic retrograde cholangiography was performed whenever stones were suspected clinically. Preoperative endoscopic retrograde cholangiography was performed in 44 patients (11%), in whom 14 (3.5%) had an endoscopic sphincterotomy with extraction of common bile duct stones. Intraoperative cholangiography was performed in only eight patients (2%) almost exclusively to acquire experience with the technique, and all cholangiograms were normal. Laparoscopic cholecystectomy was successfully completed in 96% of the patients. There were no deaths in this series, and major complications occurred in only 5% of patients. Two patients (0.5%) had a significant common bile duct injury that was recognized and successfully repaired at the initial operation. No late common bile duct strictures have been recognized. Six patients (1.5%) underwent postoperative endoscopic retrograde cholangiography for suspected common bile duct stones, with three patients requiring endoscopic sphincterotomy and stone extraction. This experience suggests that the use of preoperative and postoperative endoscopic retrograde cholangiography can be based on clinical presentation and laboratory evaluation and does not need to be performed routinely. Routine intraoperative cholangiography is not necessary in most patients undergoing laparoscopic cholecystectomy. The authors conclude that laparoscopic cholecystectomy can be performed safely with the selective use of cholangiography.

Adolescent

Biliary tract complications following laparoscopic cholecystectomy: imaging and intervention.

Radiologic studies and interventional procedures were performed in a series of 13 patients with biliary complications following laparoscopic cholecystectomy, and the results were evaluated. Two categories of ductal complication--minor and major--were found. Minor complications (n = 6) included bile leaks and bilomas; these were managed with percutaneous techniques or simple surgical repair. Major complications (n = 8), consisting primarily of common hepatic duct injuries or strictures, were markedly resistant to percutaneous therapy, requiring major surgical repair (hepaticojejunostomy). Percutaneous treatment of recurrent strictures after primary repair was undertaken in three patients. Diagnostically, radionuclide imaging appeared most helpful in screening for biliary complications of laparoscopic cholecystectomy, supplemented by endoscopic retrograde cholangiopancreatography and/or percutaneous transhepatic cholangiography for definitive diagnosis.

Adult

Effect of octreotide on sphincter of Oddi and gallbladder motility in prairie dogs.

Somatostatin and its synthetic analogue, octreotide, inhibit gallbladder emptying and cause gallstones. Whether octreotide-induced alterations in sphincter of Oddi motility contribute to this process is unknown. We, therefore, examined the effect of octreotide on fasting and protein-stimulated sphincter of Oddi motility. In 25 anesthetized prairie dogs, sphincter of Oddi motility and gallbladder pressure were monitored during the intravenous administration of octreotide, cholecystokinin (CCK) octapeptide, atropine, the intraduodenal administration of casein, and combinations of these agents. Intravenous octreotide decreased fasting sphincter of Oddi motility index both with (59 +/- 19 vs. 84 +/- 28, P less than 0.05) and without (137 +/- 31 vs. 227 +/- 42, P less than 0.05) prior cholinergic blockade with atropine. Octreotide also prevented the increases in sphincter of Oddi motility and gallbladder pressure seen with intraduodenal casein. Exogenous CCK increased sphincter of Oddi motility index and gallbladder pressure despite the simultaneous administration of octreotide alone (357 +/- 109 vs. 137 +/- 31, P less than 0.07, and 11.2 +/- 1.0 mmHg vs. 9.6 +/- 0.6 mmHg, P less than 0.05) or the combination of octreotide and atropine (317 +/- 69 vs. 59 +/- 19, P less than 0.05, and 10.1 +/- 1.6 mmHg vs. 8.5 +/- 1.4 mmHg, P less than 0.05). We conclude that both a cholinergic and an octreotide-sensitive noncholinergic pathway stimulate fasting sphincter of Oddi motility in the prairie dog.

Animals

Distribution of phosphatidylcholine molecular species between mixed micelles and phospholipid-cholesterol vesicles in human gallbladder bile: dependence on acyl chain length and unsaturation.

The partitioning of phosphatidylcholine (PC) molecular species between mixed micelles and vesicles was studied in each of seven human gallbladder biles. Biles were fractionated by Sephacryl S-300 SF gel filtration chromatography, and PC species in the micellar and vesicular fractions were quantitated by high performance liquid chromatography. Micelles were enriched in species containing unsaturated acyl groups (e.g., 16:1-18:2, 18:1-18:2, and 18:1-18:3); vesicles were enriched in more highly saturated species (e.g., 16:0-16:1, 16:0-18:1, and 18:0-18:1). Separate multivariate analyses for each bile demonstrated that the distribution of PC species between vesicles and micelles was related to the degree of sn-1 and sn-2 unsaturation, and sn-1, but not sn-2, chain length. In addition, the tendency to partition into the micellar phase was particularly marked when unsaturation was present at both the sn-1 and sn-2 positions. When this interaction was included in the multivariate analyses, the regression models accounted for virtually all of the variation in PC partitioning (for each of the seven patients r2 = 0.92-0.98, P less than 0.03). These results suggest that the partitioning of PC species between micelles and vesicles is strictly determined by sn-1 chain length and the degree of unsaturation at both the sn-1 and sn-2 positions. In light of recent reports that fatty acyl composition influences the cholesterol content of vesicles and micelles in model biles, these results raise the possibility that diet-induced alterations in the phospholipid species and the relative proportions of biliary lipid particles may influence the cholesterol-carrying capacity of bile.

Bile

Current management of benign bile duct strictures.

Benign bile duct strictures remain one of the most difficult problems encountered by the hepatobiliary surgeon. The vast majority of bile duct strictures occur as a complication of cholecystectomy. The patients may present early in the postoperative period with evidence of a biliary leak or months to years later with the development of jaundice or cholangitis. The essential first step of management consists of delineation of the proximal biliary anatomy. Current management techniques include either operative biliary reconstruction or nonoperative balloon dilatation by either the percutaneous transhepatic or endoscopic routes. The best form of surgical reconstruction of the biliary tree is a biliary-enteric anastomosis from the proximal bile duct to a Roux-en-Y limb of jejunum. In these cases, we favor the use of long-term postoperative biliary stenting using Silastic stents. Recent retrospective, nonrandomized results from our institution favor this surgical technique over nonoperative dilatation. Primary sclerosing cholangitis is a rare cause of biliary strictures. The etiology of sclerosing is unknown, but its association with ulcerative colitis and other diseases suggest an autoimmune condition. The diagnosis is confirmed by typical cholangiographic findings of multiple areas of stricture and dilatation. No medical management has proven to be successful. Surgical management for symptomatic patients includes resection of the hepatic bifurcation with long-term transhepatic stenting of the biliary tree for patients with primarily extrahepatic and/or hilar disease and with no evidence of cirrhosis. In patients with primarily intrahepatic strictures or advanced cirrhosis, liver transplantation is the treatment of choice. Benign strictures due to other causes, such as chronic pancreatitis, calculous biliary disease, sphincter of Oddi stenosis, duodenal Crohn's disease, peptic ulcer, or perivaterian duodenal diverticula usually can be managed by choledochoduodenostomy or choledochojejunostomy without long-term stenting. The management of other rare benign biliary strictures is dependent upon their extent and underlying etiology.

Catheterization

Reoperative surgery for periampullary adenocarcinoma.

In recent years, the morbidity, mortality, and long-term survival of patients undergoing surgery for periampullary adenocarcinoma have improved. These changes have prompted us to reoperate on patients who have previously undergone pancreatobiliary surgery, many of whom were initially considered to have unresectable lesions. From 1979 to 1990, 38 patients with pancreatic and 17 patients with nonpancreatic periampullary adenocarcinoma underwent reexploratory surgery at The Johns Hopkins Hospital, Baltimore, Md. Thirty-three (60%) of these 55 patients had resection at the time of second laparotomy. Of the 46 patients undergoing reexploratory surgery with an intent to resect, the overall resection rate was 72% (33), 64% (16/25) for pancreatic and 100% for nonpancreatic periampullary adenocarcinoma. Postoperative complications occurred in 21 patients (38%), but only one patient (2%) died following surgery. Mean survivals from reexploratory surgery were 6.9 months for the 22 patients with pancreatic cancer undergoing palliative surgery, 20.5 months for the 16 patients with resectable pancreatic cancer, and 33.0 months for the 17 patients with nonpancreatic periampullary adenocarcinoma undergoing resection. We conclude that in carefully selected patients, reoperative surgery for periampullary cancer (1) provides a significant resection rate, (2) can be performed safely, and (3) offers a chance for long-term survival.

Adenocarcinoma

Why does somatostatin cause gallstones?

Long-term administration of the somatostatin analogue, octreotide, is complicated by gallstone formation. Somatostatin is known to inhibit hepatic bile secretion and gallbladder emptying. However, the effect of octreotide on gallbladder bile composition remains unknown. Therefore, we tested the hypothesis that octretide would alter hepatic bile composition and cause gallbladder stasis, thereby increasing gallbladder bile solute concentrations. Fourteen control prairie dogs received daily saline injections, whereas 10 animals received 1 micrograms of octreotide subcutaneously three times per day for 5 days. Cholecystectomy and common bile duct cannulation were then performed. Octreotide increased hepatic bile concentrations of bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.05), and total protein (p less than 0.01). Rsa, an index of gallbladder stasis, was decreased (p less than 0.01) in the octreotide group. Gallbladder bile total calcium (p less than 0.05), bilirubin monoglucuronide (p less than 0.05), total bilirubin (p less than 0.01), total protein (p less than 0.05), and total lipids (p less than 0.05) were increased in the octreotide group. Animals receiving octreotide also had decreased hepatic (p less than 0.05) and gallbladder (p less than 0.001) bile pH. No differences in cholesterol saturation index were observed. These data suggest that in the prairie dog, octreotide (1) alters hepatic bile composition, (2) causes gallbladder stasis, and (3) increases gallbladder bile calcium, bilirubin, protein, lipid, and hydrogen ion concentrations. We conclude that octreotide causes alterations in gallbladder bile composition that increase the likelihood of cholesterol and calcium bilirubinate precipitation.

Animals

Cost-effectiveness of extracorporeal shock-wave lithotripsy versus cholecystectomy for symptomatic gallstones.

To evaluate the cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy for symptomatic gallstones, a model was constructed that projects charges and survival for both treatments. For a 45-year-old woman with one small stone, treatment with extracorporeal shock-wave lithotripsy rather than cholecystectomy is projected to result in an average gain of only 3 days of life and an average increase in direct medical charges of $1729 over 5 years of follow-up. The resulting marginal cost-effectiveness of extracorporeal shock-wave lithotripsy vs. cholecystectomy is $216,000 of extra charges per year of life gained with extracorporeal shock-wave lithotripsy. Extracorporeal shock-wave lithotripsy is projected to be much more cost-effective for elderly than for young patients (10-20-fold difference), but considerably less cost-effective for multiple stones than a single stone (2-4-fold difference), and less cost-effective for women than men (twofold difference). Adjusting for effects of morbidity on quality of life, extracorporeal shock-wave lithotripsy is projected to have slightly better quality-adjusted survival than cholecystectomy for the small subset of patients with one stone (by 8 to 43 days at 5 years) but not for young patients with multiple stones. It is concluded that decisions about appropriate use of extracorporeal shock-wave lithotripsy should consider the effects of patient characteristics on clinical and economic outcomes.

Aged

Bilirubin monoglucuronide promotes cholesterol gallstone formation.

Recent evidence suggests that cholesterol (Ch) solubility in bile is determined by a complex interaction of mixed micelles and lecithin-cholesterol vesicles. Bilirubin monoglucuronide (BMG), which binds to bile salts and incorporates into mixed micelles, may displace cholesterol from micelles into vesicles, thus favoring cholesterol monohydrate crystal precipitation. Therefore, we designed an experiment to test the hypothesis that BMG may enhance cholesterol gallstone formation without inducing cholesterol supersaturation. For 8 weeks, 28 adult male prairie dogs were fed either a control, nonlithogenic diet (0.03% Ch), a high carbohydrate diet (CHO) which has no cholesterol but increases hepatic bilirubin secretion, or the same CHO diet plus 0.03% Ch. Cholecystectomy was then performed, and bile was examined microscopically for stones or crystals and analyzed for BMG and biliary lipids. Cholesterol saturation index was calculated. Cholesterol gallstones were found in none of the control animals and in 13% of the CHO-fed animals. However, the addition of trace cholesterol to the CHO diet resulted in an 88% incidence of cholesterol gallstones (P less than 0.001 vs control, P less than 0.01 vs CHO, respectively). Gallbladder bile was unsaturated with cholesterol in all groups. (control = 0.65 +/- 0.05, CHO = 0.46 +/- 0.05, CHO + 0.03% Ch = 0.70 +/- 0.03). CHO feeding alone or with trace cholesterol significantly elevated gallbladder bilirubin monoglucuronide, phospholipid, and cholesterol concentrations when compared to controls. These data suggest that in the prairie dog a high carbohydrate diet with only trace amounts of cholesterol increases bilirubin monoglucuronide in gallbladder bile and causes cholesterol gallstone formation without inducing cholesterol supersaturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Short-term fasting increases biliary calcium and bilirubin.

Fasting has been associated clinically with the development of gallbladder sludge and pigment gallstones, both of which are composed primarily of calcium bilirubinate. Although fasting has been demonstrated to increase the cholesterol saturation of bile, its effect on biliary calcium and bilirubin has not been investigated. We, therefore, tested the hypothesis that short-term fasting would increase gallbladder bile calcium and bilirubin levels. Fifteen prairie dogs were studied. Seven animals were not fasted, whereas eight were fasted for 16 hr prior to acute experiments. Gallbladder and hepatic bile samples were obtained and analyzed for calcium, bilirubin, pH, and biliary lipids. Gallbladder bile ionized calcium levels were significantly increased in fasted animals (1.7 +/- 0.2 mM) compared to those in nonfasted animals (1.1 +/- 0.1 mM). Similarly, total calcium (4.3 +/- 0.5 mM vs 2.3 +/- 0.3 mM), total bilirubin (63 +/- 12 microM vs 29 +/- 8 microM), and bilirubin monoglucuronide (58 +/- 10 microM vs 22 +/- 8 microM) were significantly increased in the fasted group. Fasted animals were also noted to have an increased biliary cholesterol saturation index (0.57 +/- 0.04 vs 0.36 +/- 0.03) and decreased biliary pH (6.9 +/- 0.1 vs 7.6 +/- 0.1). These data indicate that in the prairie dog short-term fasting results in significant alterations in gallbladder bile composition. The increased concentrations of gallbladder calcium and bilirubin observed in these experiments may account, in part, for the formation of pigment gallstones and gallbladder sludge seen clinically with prolonged fasting.

Animals

Transduodenal exploration of the common bile duct in patients with nondilated ducts.

Exploration of the small common bile duct can be technically difficult and is associated with a significant risk of ductal injury or late stricture, or both. Transduodenal common duct exploration after sphincteroplasty (TCDE/S) is an alternative method of duct exploration that avoids choledochotomy. Cholecystectomy followed by TCDE/S was performed upon 28 patients with nondilated ducts and suspected choledocholithiasis. Common duct stones were retrieved in 17 patients. Failure to retrieve stones in the remaining 11 patients was attributed to either false-positive results of cholangiography, forceful passage of stones into the duodenum during the initial insertion of a Fogarty catheter through the cystic duct or a false-negative finding at duct exploration. There was no perioperative mortality. Two patients had asymptomatic postoperative hyperamylasemia. One patient had postoperative pancreatitis, hyperbilirubinemia and cholangitis that resolved with antibiotic therapy by the eighth postoperative day. Other complications included wound infection, delayed gastric emptying, pneumonia and otitis media. The over-all morbidity rate was 28.6 per cent. Long term follow-up was obtained in all 28 patients. All patients in the follow-up group are free of recurrent biliary tract disease. TCDE/S appears to be a safe and effective method of exploring the nondilated common bile duct.

Adult

The effect of calcium on gallbladder absorption.

The absorption of water and electrolytes is an important physiologic function of the gallbladder which is altered during gallstone formation. Extracellular calcium and calcium channel antagonists are known to affect intestinal absorption, yet their effect on gallbladder absorption is less well defined. We, therefore, tested the hypothesis that changes in extracellular calcium or in calcium channels would alter gallbladder absorption. New Zealand white rabbit gallbladders were removed, filled with a modified Krebs buffer (Ca2+ = 0.7 mM), and suspended in an oxygenated bath of the same buffer. Water absorption was determined gravimetrically by obtaining serial gallbladder weights at 10-min intervals. After a 40-min control period, the serosal bathing solution was changed to one of four experimental solutions (n = 6 for each group): Ca2+ = 0.25, 0.7, or 1.2 mM or Ca2+ = 0.7 mM plus 0.1 mM verapamil. Absorption was determined during an 80-min experimental period with results expressed as the percentage change in gallbladder absorption compared to that of the control period. The 0.25, 0.7, and 1.2 mM Ca2+ groups did not show a significant change in absorption rate from their respective control rates. However, the verapamil group did demonstrate a significant (P less than 0.05) decrease in absorption rate of -69 +/- 8% by the end of the experimental period. These data demonstrate that verapamil inhibits gallbladder absorption while changes in serosal calcium concentration have no effect. We conclude that calcium channels and intracellular calcium may play an important role in modulating gallbladder absorption.

Absorption

Altered bile composition during cholesterol gallstone formation: cause or effect?

Gallbladder stasis, increased gallbladder absorption, and elevated biliary levels of calcium, hydrogen ion, and bilirubin have been implicated as factors potentially critical to cholesterol crystal precipitation. Previous studies, however, have analyzed bile only when crystals or gallstones have already formed. Therefore, we tested the hypothesis that changes in bile composition are a late effect, occurring only after crystal formation. Adult male prairie dogs were fed a standard nonlithogenic control diet (n = 7) or a lithogenic 1.2% cholesterol diet for 5, 9, or 14 days to cause cholesterol saturation (n = 7), cholesterol monohydrate crystals (n = 7), or gallstones (n = 7). Gallbladder bile was examined microscopically for crystals, and analyzed for ionized calcium, bilirubin, pH, total protein, and biliary lipids. The ratio of gallbladder to hepatic bile radiolabeled cholic acid specific activity (Rsa) was calculated as an index of gallbladder stasis. Cholesterol saturation index was calculated. The results demonstrate that increased gallbladder bile cholesterol saturation and total protein concentration precede cholesterol monohydrate crystal precipitation. However, changes in gallbladder ionized calcium, unconjugated bilirubin, pH, stasis, and absorption were noted only after crystals and gallstones had already formed. These data indicate that alterations in gallbladder bile calcium, bilirubin, pH, stasis, and absorption are not early changes, but occur simultaneously with or after crystal formation. Increased biliary protein, however, which was elevated prior to nucleation, may be an important mediator of cholesterol precipitation in cholesterol-saturated bile.

Animals

The interposition mesocaval shunt.

The interposition mesocaval C-shunt is an excellent alternative for the management of bleeding esophageal varices. The comparable operative mortality, long-term survival, and minimal operative time and blood loss make it the emergency shunt of choice. The C-shunt modification has improved long-term patency and ease of operation. The interposition mesocaval shunt also is increasing in importance as the best portosystemic shunt in those patients who may eventually require liver transplantation.

Esophageal and Gastric Varices