Iatrogenic and noniatrogenic extrahepatic biliary tract injuries: a multi-institutional review.

Traumatic and iatrogenic extrahepatic biliary tract injuries are rare but may lead to exceedingly morbid complications. Traumatic extrahepatic biliary tract injuries represent less than 1 per cent of all traumatic injuries. Iatrogenic injuries result in 0.2 to 1 per cent of laparoscopic or open cholecystectomies. The objective of this study was to review the incidence of biliary tract injuries--iatrogenic as well as traumatic--and their subsequent management. A multi-institutional chart review was done including Louisiana State University Health Sciences Center (LSUHSC)-Shreveport, LSUHSC-Monroe, and Richland Parish medical centers. Charts were reviewed for patients with iatrogenic biliary tract injuries and those with biliary tract injuries related to noniatrogenic trauma. The etiology of the biliary tract injury, symptoms of injury, pertinent laboratory and radiologic studies, injury-to-diagnosis time, type of biliary tract injury, injury management, days hospitalized, intensive care unit stay, and complications were reviewed. There are 1500 trauma patients admitted to LSUMC-Shreveport each year. The incidence of biliary tract injury in trauma patients admitted to LSUMC is 0.1 per cent. Traumatic injuries were classified according to the injury scale by Mattox et al. (Trauma 1996; Vol 515). There were five Type II, four Type IV, and two Type V injuries. Five patients underwent cholecystectomy, three had endoscopic retrograde cholangiopancreatography with stent placement, and two had choledochojejunostomy; one patient died from associated injuries. There were no complications of repair. Approximately 220 cholecystectomies are done at LSUMC-Shreveport each year. Eighty-eight per cent are laparoscopic, and 12 per cent are open. The incidence of iatrogenic biliary tract injuries at LSUMC-Shreveport during the past 8 years was 0.2 per cent. Immediate diagnosis of iatrogenic injuries was made in five of 17 cases and eight of 11 trauma cases. Laparoscopic injuries were classified by the Way injury classification (Stewart L, Way LW. Arch Surg 1995;130:1123). There were one Type I, one Type II, and nine Type III injuries. Treatment included suturing of the laceration (n = 1), hepaticojejunostomy (n = 8), and primary repair (n = 2). Open injuries were classified using the Bismuth classification. There were one Type I and three Type III injuries. All were treated with hepaticojejunostomy. There were two iatrogenic injuries unrelated to cholecystectomy. One patient suffered a perforation of the gallbladder during laparoscopic nephrectomy. This patient subsequently underwent cholecystectomy and has done well. The second patient suffered ligation of the intraduodenal portion of the common bile duct during hemigastrectomy and oversewing of a duodenal ulcer. This patient underwent hepaticojejunostomy and has done well. Complications of iatrogenic injury repair included leaking of a repaired laceration (n = 1), failed hepaticojejunostomy (n = 1), and an anastomotic stricture after hepaticojejunostomy (n = 1). Laparoscopic injuries by LSUMC hospitals is 0.2 per cent. Extrahepatic biliary tract injuries resulting from open cholecystectomy were diagnosed later than those occurring during laparoscopic cholecystectomy and were most likely to result in stricture formation. Repair of Way Type II and III injuries is associated with a higher complication rate. Hepaticojejunostomy has a complication rate of 15 per cent. Minor common duct lacerations are amenable to conservative therapy with oversewing and/or endoscopic retrograde cholangiopancreatography with stent placement. Repair of extrahepatic biliary tract injuries with hepaticojejunostomy at a level of good blood supply remains our gold standard for treatment of more severe injuries and strictures.

Pancreatic transplantation and subsequent graft surveillance by pancreatic portal-enteric anastomosis and temporary venting jejunostomy.

OBJECTIVE: To evaluate portal-enteric (PE) pancreas and kidney transplantation with venting jejunostomy (VJ) for its efficacy, safety, and reproducibility. SUMMARY BACKGROUND DATA: Simultaneous pancreas and kidney transplantation for patients with long-standing insulin-dependent diabetes mellitus that progresses to renal failure has revolutionized their treatment and quality of life. A current clinical focus is to refine the technical aspects of this procedure. Simultaneous pancreas and kidney transplantation with PE anastomosis with VJ appears to offer several advantages over bladder drainage. VJ allows initial decompression of the enteric anastomosis, monitoring of pancreatic function by ostomy amylase, and simple access for endoscopic evaluation and biopsy of the allograft. METHODS: Simultaneous pancreas and kidney transplantation with VJ was performed in 21 patients from December 1996 to October 2000 at Willis Knighton/LSU Regional Transplant Center. All patients had long-standing insulin-dependent diabetes mellitus and subsequent renal failure. They were evaluated at the time of surgery by a multidisciplinary transplant team and monitored for numerous factors, including length of hospital stay, immunosuppressive regimen, and ischemia times. All patients had intermittent visual and biochemical evaluation of pancreatic secretions monitored by means of the VJ. RESULTS: Of the 21 patients, 10 were women and 11 were men. Four patients were black and 17 were white. The mean age at transplantation was 38 years; average human leukocyte antigen (HLA) match was one; and average cold ischemia time was 12 hours. The median hospital stay was 16 days. Four episodes of postoperative bleeding requiring exploration occurred in four patients. Postoperative wound infections developed in four patients. There were 12 episodes of rejection in nine patients. All patients with suspected acute pancreatic rejection underwent endoscopy by means of the VJ and duodenal biopsy for evaluation. Two patients lost pancreatic function subsequent to kidney failure, one secondary to noncompliance and the other as a result of hemolytic-uremic syndrome. Patient, kidney, and pancreatic survival rates were 100%, 90%, and 90%, respectively. The mean follow-up period was 25 (range 2-48) months. CONCLUSION: The authors believe that PE pancreatic drainage with VJ is a more physiologic method to perform pancreatic transplantation than bladder drainage. PE drainage allows rapid diagnosis of acute rejection and anastomotic leak and provides a simple way to monitor ostomy amylase and transplant duodenal bleeding. This technique is safe and has minimal associated complications.

Both ischemic and pharmacological preconditioning decrease hepatic leukocyte/endothelial cell interactions.

BACKGROUND: Ischemic preconditioning has been shown to protect some tissues from ischemia/reperfusion (I/R) injury. Adenosine is believed to play an important role by attenuating leukocyte-endothelial cell adhesive interactions. Dipyridamole increases adenosine bioavailability. The purpose of this study was to evaluate the effects of mechanical (MPC) and pharmacological preconditioning (PPC) on leukocyte endothelial cell interaction in hepatic I/R injury. METHODS: C57BL6 mice were subjected to 30 min of ischemia to the left lobe of the liver. Groups tested at 30 min, 2, 5, 12, and 24 hr of reperfusion had 1) sham laparotomy (n = 10, 2) I/R (n = 25), 3) ischemic preconditioning with 5 min of ischemia and 10 min reperfusion before I/R (n = 25), and 4) (PPC) with dipyridamole (n = 25). Intravital microscopic examination was used to assess leukocyte/endothelial cell adhesion. Blood was drawn for leukocyte counts and liver function tests. RESULTS: A significant decrease in leukocyte rolling was observed at 30-min and 5-hr reperfusion intervals in the PPC and ischemic preconditioning groups compared with the I/R group. A significant decrease in leukocyte saltation was also observed in the PPC and MPC groups at 2, 5, and 12 hr of reperfusion when compared with the I/R group. aspartate aminotransferase was significantly decreased in the 5-hr preconditioning groups. There was not a significant decrease in the white blood cell count because of PPC or MPC vs. I/R CONCLUSIONS: Preconditioning decreases endothelial/ leukocyte interaction and reduces liver damage as measured by aspartate aminotransferase. These data prove that IPC and PPC provide some degree of hepatic protection in I/R injury.

P-selectin contributes to the initial recruitment of rolling and adherent leukocytes in hepatic venules after ischemia/reperfusion.

We have recently reported that hepatic ischemia/reperfusion (I/R) is associated with a biphasic increase in the expression of P-selectin in the liver microvasculature, with peak expression levels observed at 20 min and 5 h after reperfusion. This I/R-induced upregulation of P-selectin expression is accompanied by leukocyte-endothelial cell adhesion in terminal hepatic venules (THV). The objective of this study was to determine whether the early expression of P-selectin contributes to the initial recruitment of rolling and adherent leukocytes in THV after liver I/R. Left hepatic lobe ischemia was induced for 30 min in anesthetized C57B1/6 and P-selectin knockout (KO) mice. The number of rolling, saltating, and adherent leukocytes in THV was measured at 0, 15, 30, 60, and 120 min after reperfusion using intravital video microscopy. Hepatic I/R elicited significant increases in the number of rolling, saltating, and adherent leukocytes, with peak values observed at 30 min after reperfusion. All of these responses were absent in P-selectin KO mice and in C57B1/6 mice treated with a blocking antibody to P-selectin. Our findings suggest that P-selectin is the primary determinant of leukocyte-endothelial cell adhesion observed in hepatic venules in the initial period after I/R. Hence, this adhesion molecule may represent a target for therapeutic intervention in liver transplantation and other conditions associated with hepatic I/R.

Are all successful renal transplants really successful?

We previously described a small group of renal transplant recipients considered to have successful allografts statistically, but who did not benefit clinically. These were patients in whom the grafts survived greater than 6 months but less than 3 years. This expanded study evaluates 179 consecutive renal transplant recipients divided into three groups. Group 1 (n = 18), group 2 (n = 41), and group 3 (n = 120) have patients with graft survival less than 6 months, between 6 months and 3 years, and greater than 3 years, respectively. Mean age, cause of renal failure, HLA match, and immunosuppressive regimen were not statistically different in any group. The number of acute rejection episodes, number of hospitalizations, and number and seriousness of complications were significantly greater in group 2 patients compared with the other groups. Patients in group 2 experienced five times the number of acute rejections (P < 0.0001), three times the number of hospitalizations (P < 0.0001), and two times the number of complications (P < 0.0001) compared with group 3 patients. In conclusion, those transplant recipients whose grafts survived longer than 6 months but less than 3 years were the most unfortunate. They experienced repeated and serious complications and spent many days in the hospital at great expense. A study with more sensitive methods of detecting presensitization might impact on graft performance in the future.

The role of ischemic preconditioning in the recruitment of rolling and adherent leukocytes in hepatic venules after ischemia/reperfusion.

BACKGROUND: We have recently shown that hepatic ischemia/reperfusion (I/R) results in rolling and adherence of leukocytes in terminal hepatic venules (THV) followed by hepatic enzyme elevation and tissue destruction. The objective of this study was to determine the effect of ischemic preconditioning on the recruitment of leukocytes in THV after liver I/R. METHODS: Left hepatic lobe ischemia was induced for 5 min (preconditioning) in anesthetized C57B1/6 mice followed by reperfusion for 10 min and then prolonged ischemia for 30 min. The number of rolling, saltating, and adherent leukocytes in THV was measured at 0.5, 2, 5, 12, and 24 h after reperfusion using intravital video microscopy. Matching sham groups were evaluated after 30 min of ischemia. RESULTS: Hepatic I/R elicited significant increases in the number of rolling, saltating, and adherent leukocytes, with peak values observed at 30 min and 5 h after reperfusion. All of these responses were significantly attenuated in mice undergoing ischemic preconditioning. Rolling leukocytes in THV following I/R without preconditioning reached peak levels of 25.2 +/- 1.4 leuk/2 min (leukocytes/2 min) at 30 min reperfusion and 31.4 +/- 1.5 leuk/2 min at 5 h reperfusion. With ischemic preconditioning these values fell to 12.3 +/- 0.9 leuk/2 min and 14.4 +/- 1.0 leuk/2 min, respectively (P < 0.001). Similarly, adherent leukocytes in nonpreconditioned mice reached peak values of 4.8 +/- 1.3 leuk/2 min at 30 min reperfusion and 8.3 +/- 1.2 leuk/2 min at 5 h reperfusion compared with 2.0 +/- 1.5 leuk/2 min and 1.6 +/- 1.1 leuk/2 min in preconditioned mice, respectively (P < 0.001). CONCLUSION: Ischemic preconditioning attenuates the initial events leading to leukocyte-mediated hepatic destruction following I/R injury. Delineating these mechanisms may play an important role in hepatic transplantation, resection, shock, and sepsis.

Prior exercise suppresses the plasma tumor necrosis factor response to bacterial lipopolysaccharide.

This study was initiated to determine the effect of physical exercise on the in vivo tumor necrosis factor-alpha (TNF) response to Escherichia coli lipopolysaccharide (LPS). Rats familiarized with treadmill running and surgically implanted with vascular catheters were either not exercised or exercised to near exhaustion (mean run time of 102 +/- 13 min) before intravenous LPS challenge (1 mg/kg; lethality of dose is 10-20% in 24 h). Compared with time-matched nonexercised control rats, exercised rats had increased heart rates, plasma lactate, and plasma corticosterone and decreased plasma glucose at the conclusion of exercise. In response to LPS, both groups became hypotensive, exhibited transient hyperglycemia, and sustained hyperlactacidemia. By 30 min post-LPS, plasma corticosterone levels were similar in the two groups. Nonexercised rats exhibited a normal plasma TNF response to LPS with the peak value (10,400 +/- 2,000 U/ml) occurring 90 min after LPS challenge. In contrast, the TNF response in rats exercised before LPS administration was blunted to 17% of the nonexercised group, with the peak occurring at an earlier time after LPS. Addition of recombinant murine TNF to postexercise plasma was fully expressed. The TNF response remained attenuated when LPS was administered up to 6 h after completion of exercise, but it returned to normal in rats allowed to recover for 24 h. The results demonstrate that exercise, perhaps as a stress modality, markedly suppresses the systemic TNF response that is normally observed in response to LPS challenge.