[Metastatic lesions to the pancreas. When is resection reasonable?]. / Metastasen im Pankreas. Wann ist eine Resektion sinnvoll?

BACKGROUND: The significance of pancreatic resection for pancreatic metastatic lesions has not yet been sufficiently investigated. A retrospective analysis of patients undergoing pancreatic resections for pancreatic metastases was conducted. MATERIAL AND METHODS: Twenty patients were resected due to metastatic lesions to the pancreas. Histopathological findings were: renal cell carcinoma (n=9), colon carcinoma (n=1), malignant schwannoma (n=2), leiomyosarcoma (n=2), teratocarcinoma (n=1), adenocarcinoma of the oesophagus (n=1), gallbladder carcinoma (n=1), malignant melanoma (n=1), gastrointestinal stromal tumor (n=1), and spindle cell tumor (n=1). Operative procedures were standard pancreaticoduodenectomy (n=6), pylorus-preserving pancreaticoduodenectomy (n=6), and distal pancreatectomy (n=8). RESULT: The overall 5-year survival rate was 61%, for patients with renal cell carcinoma 100%. CONCLUSION: Pancreatic metastasectomy is a reasonable therapeutic option in suited patients. Patients with pancreatic metastases of renal cell carcinoma achieved excellent prognoses after radical resection.

Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat.

The present study was designed to determine whether .N = O produced in vivo during the rejection of histoincompatible tissues might permit serum NO2-/NO3- levels to serve as markers of a rejection reaction. Rat syngeneic and allogeneic liver, heart, bone marrow/spleen cell, small bowel, skin, and sponge matrix grafts were performed and the stable end-products of .N = O, NO2-/NO3-, were serially assayed in the serum of the grafted animals. A significant rise of serum NO2-/NO3- levels in the allografted animals preceded the onset of clinical signs of rejection or graft-versus-host disease, with the exception of the skin and sponge matrix graft models, where elevated serum NO2-/NO3- levels were never observed. In all transplant models, normal serum NO2-/NO3- levels were observed at all times in animals that received syngeneic grafts. Furthermore, treatment of allograft recipients with the immunosuppressive agents FK 506 or cyclosporine A inhibited .N = O production. Determination of serum creatinine levels demonstrated that the elevated serum NO2-/NO3- levels were not caused by kidney dysfunction. Serum NO2-/NO3- levels might be useful early serum markers of the initiation of a rejection reaction or graft-versus-host disease when functional markers of graft dysfunction are not apparent.

Adult living donor liver transplantation: living donation of the right liver lobe.

BACKGROUND: Adult living donor liver transplantation (LDLT) has become a routine treatment option for patients waiting for liver transplantation. In European and North American countries, LDLT for adult recipients is mainly performed with right lobe grafts. Indications, when compared to deceased donor liver transplantation, are controversial. MATERIALS AND METHODS: In our institution, patients suffering from hepatocellular carcinoma in cirrhosis, non-resectable hilar cholangiocarcinoma, viral hepatitis associated cirrhosis, as well as cholestatic liver and biliary disease are considered good candidates for LDLT. RESULTS: In this overview, donor evaluation, graft selection, and the donor operation with special regard to operative techniques and strategies are discussed. For visualization, a 5-min video sequence of the standard donor operation as performed in our institution is attached. CONCLUSION: Given the ongoing shortage of donor organs, adult LDLT has become a routine treatment option for patients waiting for liver transplantation. The associated inevitable risk for the healthy donor, however, remains ethically controversial.

Fast tracking in liver transplantation: which patient benefits from this approach?

In liver transplantation, "fast tracking" means postoperative extubation in the operating theater immediately after surgery. This procedure was performed in a series of 837 adult liver transplant recipients between January 1997 and April 2005, proving to be safe and feasible in almost 80% of patients without increasing the incidence of reintubation. This patient population experienced a significantly higher survival compared to patients who were extubated in the intensive care unit. Consequently, fast tracking should become the standard procedure after orthotopic liver transplantation. However, special attention is required for recipients with acute liver failure, retransplantation, Child C status, or complicated surgery in terms of increased transfusion of red blood cells. These patients do not participate in fast-tracking protocols, as demonstrated by a uni- and multivariate logistic regression analysis. Moreover, ROC analysis revealed that only intraoperative transfusion of

[A method for reassessment of cost-intensive cases in visceral surgery. Results of project by the German Society for Visceral Surgery]. / Methode zur Abbildung kostenintensiver Fälle in der Viszeralchirurgie. Ergebnisse des DRG-Projekts der Deutschen Gesellschaft für Viszeralchirurgie.

Since the introduction of diagnosis-related groups (DRGs) many surgical departments report inappropriate reimbursement for complex cases and a shift in costly cases. To evaluate this situation, the German Society for Visceral Surgery inaugurated the present cost calculation project. In three university hospitals for 50 cases each, we depicted possible cost separators and utilized the complete cost calculation data (so-called Paragraph 21 data set) to test these separators. We identified "admission from another hospital", "severe surgically relevant concomitant disease", and "reoperation during the same hospital admission". The last was considered the economically most significant and medically most valid factor and was submitted as a possible modification to the german DRG system. The proposed cost separator "reoperation during the same hospital admission" was introduced into the DRG system after validation and leads to better allocation of reimbursements to complex and costly cases.

Acute renal failure after liver transplantation: incidence, etiology, therapy, and outcome.

Acute renal failure (ARF) was a frequent complication after orthotopic liver transplantation (OLT) when ARF was defined by a calculated glomerular filtration rate decrease of >50% or by a doubled serum creatinine above 2.5 mg/dL within the first week after OLT. We analyzed 1352 liver transplant recipients in retrospective fashion with regard to the incidence, etiology, therapy, and outcome of ARF; 162 patients developed ARF within the first week after OLT (12%), among whom 157 patients (97%) were recompensated by postoperative day 28. Altogether 52 patients (32%) received an average of 6 hemodialysis treatments, excluding the 5 patients (3%) who developed end-stage renal failure. Risk factors for this complication included hepatorenal syndrome type II, a glomerular filtration rate of <50 mL/min, and a diagnosis of hepatitis C.

[Carcinomas of the distal bile duct]. / Extrahepatische distale Gallenwegskarzinome.

Malignancies of the biliary tree are classified into three groups according to location: intrahepatic, central (perihilar), and distal. Of all cholangiocarcinomas, 25% are located distally and can be subdivided into middle and lower bile duct carcinomas. Surgical approaches for achieving tumor-free resection margins (R0) are directly associated with the origin of the tumor. Intrahepatic and central cancers usually must be treated by liver surgery, whereas the majority of distal cholangiocarcinomas require pancreaticoduodenectomy. In case of a small, middle bile duct carcinoma, exclusive extrahepatic bile duct resection without pancreatic resection can be adequate. Five-year survival after radical resection is about 25%. Cancer of the distal bile duct has to be distinguished from ductal adenocarcinoma of the pancreas and carcinoma of the ampulla of Vater. Curative surgery is possible if the tumor is diagnosed early and radical resection is feasible. In this context, the role of an extended lymph node dissection remains unclear. To improve survival, future studies are needed to evaluate the role of novel adjuvant strategies (i.e., gemcitabine, capecitabine).

Primary immunosuppression with tacrolimus after liver transplantation: 12-years follow-up.

The early safety and efficacy of tacrolimus after liver transplantation has been shown in two multicenter trials. Herein, we report our single-center long-term follow-up of a randomized controlled trial. As part of a European multicenter trial, 121 patients entered the study at our institution and were randomly assigned to receive either tacrolimus and steroids (n=61) or a quadruple protocol (n=60) using ciclosporin A, steroids, azathioprine, and antithymocyte globulin (ATG). Twelve-year figures of patient survival were 74% in the tacrolimus group and 66% in the cyclosporine-based group. Graft survival after 12 years was 69% in the tacrolimus group compared to 56% in the cyclosporin-based group (not significant, p=0.15). The total rate of graft loss and retransplantation decreased significantly in the tacrolimus arm (p<0.05). De novo malignancies increased significantly in the ciclosporin-based group and dominated as single cause of death beyond 5 years posttransplant. The use of tacrolimus after liver transplantation resulted in a decreased rate of graft loss over the long-term. An increased number of de novo malignancies in the ciclosporin-based group may be attributable to the use of ATG as induction therapy.

Anti-TNF-alpha therapy for acute rejection in intestinal transplantation.

INTRODUCTION: We present our experience with infliximab rescue therapy for steroid- and OKT3-resistant rejection after intestinal transplantation (ITx). METHODS: Twelve ITx and one multivisceral transplant recipients were immunosuppressed with tacrolimus, rapamycin, daclizumab, steroids (n = 10) or tacrolimus, campath, and steroids (n = 3). RESULTS: In two patients, severe acute rejection did not resolve despite steroid bolus therapy plus 5 to 10 days of OKT3 treatment. Signs of moderate rejection persisted in the distal portions of the grafts. Treatment with infliximab, a chimeric anti-TNF-alpha antibody (four infusions of 3 mg/kg body weight), induced a complete remission of histological and clinical signs of rejection. Two further patients with steroid-resistant rejection received two courses of infliximab (3 mg/kg body weight) as antirejection therapy. All rejection episodes resolved completely. CONCLUSIONS: Infliximab effectively treats steroid and OKT3 resistant acute rejection episodes of intestinal transplantations.

Liver transplantation for primary biliary cirrhosis: influence of primary immunosuppression on survival.

INTRODUCTION: Liver transplantation is the only established curative therapy for end-stage primary biliary cirrhosis (PBC). However, the influence of primary immunosuppression on long-term patient and graft survival is still controversial. PATIENTS AND METHODS: Among 1372 patients who underwent liver transplantation from April 1989 to January 2001, 95 (6.9%) suffered from PBC. The primary immunosuppression consisted of cyclosporine (CyA; n = 56) and tacrolimus (FK; n = 39). RESULTS: The median survival of all PBC patients at 5 years was 92% and at 10 years, 90%. There was no difference between the two primary immunosuppression agents. Seven patients died, including five in the cyclosporine group (median = 25 months) and two in the tacrolimus cohort (median = 37 months). One CyA patient group died due to PBC recurrence. Seven patients underwent retransplantation without any difference in primary immunosuppression (CyA 7%; FK 10%). Fifty patients developed an acute rejection episode (CyA 57%; FK 46%); 2 patients, chronic rejection (CyA 2%; FK 4%). Fifty-five patients developed AMA titers after liver transplantation (CyA 66%; FK 46%). Patients presented cyclosporine-based regimens showed significantly (P = .001) more side effects. CONCLUSION: Long-term follow-up after liver transplantation for PBC shows excellent organ and patient survival. The choice of the primary immunsuppressant had no significant influence on patient survival, PBC-related graft loss, or development of acute or chronic rejection episodes.

Repeated steroid pulse therapies in HCV-positive liver recipients: significant risk factor for HCV-related graft loss.

BACKGROUND: The optimal immunosuppressive regimen for HCV-positive liver transplant recipients has not been established. Treatment for acute cellular rejection (ACR) with steroids is associated with increased viral replication and graft hepatitis. We retrospectively analyzed 232 patients after orthotopic liver transplantation (OLT) for HCV cirrhosis to determine the influence of methylprednisolone pulse therapy on long-term outcome after OLT. METHODS: Two hundred thirty-two liver transplants were performed in HCV-positive recipients between 1989 and 2001. Median follow-up was 4.4 years and median age of patients was 53 years (range 15 to 72 years). Immunosuppression consisted of tacrolimus (Tac) or cyclosporine (CyA) in different protocols. All rejection episodes were histologically proven. RESULTS: Twenty-eight of 232 (12.06%) graft losses were due to severe hepatitis C reinfection. Of 232 patients, 105 showed a minimum of one episode of ACR (45.25%). Of 232 patients, 71 (30.6%) received methylprednisolone pulse therapy once and 15 of 232 required OKT3 treatment for steroid-resistant rejection (6.4%). Of 232 patients, 19 (8.1%) required repeated steroid pulse therapy due to more than one episode of ACR. In patients with more than one episode of ACR, the risk of HCV-related graft loss was significantly enhanced (6/19, P < .05). The primary immunosuppression had no influence on the outcome in our data. CONCLUSION: Our data show that outcome of HCV-positive patients who require repeated steroid pulse therapy (RSPT) for ACR is significant worse than that in patients with a single pulse therapy. Therefore RSPT should be avoided in HCV-positive transplant recipients. New strategies to manage acute rejection are required for these patients.

Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration.

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.

Withdrawal of steroids: a randomized prospective study of prednisone and tacrolimus versus mycophenolate mofetil and tacrolimus in liver transplant recipients with autoimmune hepatitis.

The aim of this study was to evaluate the success of steroid (PRED) withdrawal due to replacement by mycophenolate mofetil (MMF) in orthotopic liver transplant (OLT) recipients with autoimmune hepatitis (AIH). Thirty patients with AIH > 12 months after OLT randomized to receive either PRED and tacrolimus (TAC) or MMF and TAC were followed for 24 months. Withdrawal of steroids showed no difference regarding graft and patient survival. Also we demonstrated significantly lower glucose levels with lower HbA1c and a reduced need for insulin as well as a significantly lower serum cholesterol in the MMF group. Patients without steroids showed a lower incidence of osteopenia. Maintenance therapy in OLT patients with AIH may be performed safely using MMF instead of prednisone.

[Malignant epithelioid hemangioendothelioma of the liver. Results of surgical treatment strategies]. / Malignes epitheloides Hämangioendotheliom der Leber. Ergebnisse der chirurgischen Behandlung.

BACKGROUND: Malignant epithelioid hemangioendothelioma is a rare vascular tumor described mostly in soft tissue, lungs, or liver. The outcome after a wide variety of therapeutic measures, ranging from extended surgical therapy to no therapy, is reported to be variable. Therefore, we reviewed our experience with resective therapy for this rare liver tumor, including orthotopic liver transplantation. MATERIAL AND METHODS: During a period of 5 years, seven patients with the histological diagnosis of hepatic epithelia hemangioendothelioma were seen. In five of them, the liver pathology was detected at random, and all patients were prospectively followed. The therapeutic measures and course of disease are given as case reports. RESULTS: Three patients received formal liver resection and two received liver grafts, one partial and one whole. One further patient is scheduled for transplantation and one is undergoing alternative therapy, with the tumor remaining stable. All resected patients recovered quickly and are alive and well 2 months to 4 years later without signs of tumor recidivism. CONCLUSION: Anatomic liver resection, or in the case of diffuse tumor spread, orthotopic liver transplantation, show favorable long-term results for the treatment of hepatic epithelioid hemangioendothelioma. Therefore, surgical therapy is proposed as the treatment of choice for this entity.

Initial experience with the use of fibrin sealant for the fixation of the prosthetic mesh in laparoscopic transabdominal preperitoneal hernia repair.

INTRODUCTION: Laparoscopic inguinal hernia repair offers more rapid recovery and less pain than with the traditional open approach. However, injury to the nerves of the lumbar plexus with subsequent chronic pain or neuralgia has a reported incidence of 2% during laparoscopic hernia repair, particularly when the transabdominal preperitoneal technique (TAPP) is used. These complications are inherent to the use of staples for fixation of the mesh. To avoid nerve irritation, we considered the use of fibrin sealant for the fixation of the mesh instead of staples. The aim of this study was to evaluate this technique and to compare the short-term follow-up of these patients with patients who underwent the staple repair technique. This is the first reported use of fibrin sealant in laparoscopic TAPP hernia repair. METHOD: Between September and November 2004, we performed 17 consecutive laparoscopic hernia repairs (TAPP) in 14 patients (3 bilateral hernias) with primary hernias. The prosthetic mesh was fixed (10 x 15 cm) with 1 ml fibrin. The fibrin was applied using a special laparoscopic applicator. The peritoneum was closed with absorbable sutures. The postoperative course of these patients was compared with a cohort of matched patients who received the traditional staple fixation of the prosthetic mesh. RESULTS: Patients were evaluated at a median follow-up of 10.4 months (3.8-16.0 months). All patients underwent postoperative physical examinations. No recurrent hernia was found. There were 2 seromas and one hematoma in the stapled group. In the stapled group, one patient had pain in the area of the lateral femoral cutaneous nerve. There was no postoperative complication in the non-stapled group. CONCLUSION: Fibrin fixation of the mesh during laparoscopic transabdominal preperitoneal inguinal hernia repair is feasible without higher risk of recurrences. In addition the fibrin fixation method may decrease postoperative neuralgia and reduce the incidence of postoperative seromas and hematomas.

[Treatment of iatrogenic bile duct lesions from laparoscopic cholecystectomy]. / Behandlung von iatrogenen Gallengangverletzungen im Rahmen der laparoskopischen Cholecystektomie.

Injuries of the biliary tract following laparoscopic cholecystectomy have increased with the widespread use of the procedure. Compared to the conventional open choelycstectomy, the incidence of bile duct injuries is at least twofold higher after the laparoscopic procedure. A number of risk factors for the occurrence of bile duct injuries have been well described, including severe inflammation, bleeding, anatomical variations and lack of surgical experience. The appropriate management of bile duct injuries depends on the time of diagnosis after the injury and the type of injury. While peripheral leakages and short strictures can be treated endoscopically, extended injuries and long strictures require surgical reconstruction. The best long-term results are achieved with a tension-free, end-to-side mucosa-to-mucosa Roux-Y hepaticojejunostomy.

Clinical course, morphology, and treatment of chronically rejecting small bowel allografts.

As acute rejection episodes are most frequently prevented or controlled in clinical organ transplantation, chronic rejection processes have become the major reason for late dysfunction and eventual loss of the allograft. The recent reports on successful clinical intestinal transplantation prompted us to investigate chronic rejection processes that may arise after the initial control of acute rejection. Using the strongly histoincompatible ACI-->LEW rat strain combination and serial graft biopsies after limited initial immunosuppressive therapy with cyclosporine, we defined the clinical and pathomorphologic course of chronic rejection of orthotopic small bowel allografts. Differing from acute rejection, the bowel wall (especially the mucosa and submucosa) was not the primary target of chronic rejection. We observed progressive destruction of the Peyer's patches and the mesenteric lymph nodes of the graft--a process which began during the 4-week course of CsA--and infiltration and destruction of graft mesenteric vessels. Testing the immunosuppressive drugs FK506 and CsA for their efficacy to ameliorate ongoing chronic rejection, we found that a short course (5 days) of FK506 was more effective than a second 4-week course of CsA. However, while allograft function recovered sufficiently to allow a temporary improvement of the recipient's global nutritional state, pathomorphologic graft changes failed to reverse substantially. Eventually all grafts failed due to progressive chronic rejection.

Nitric oxide production by mouse sponge matrix allograft-infiltrating cells. Comparison with the rat species.

We have recently demonstrated in the rat species that sponge matrix allograft infiltrating cells spontaneously produce nitric oxide (.N = 0) and this .N = 0 production precedes the development of CTL. Compared with our experience in the mouse species, the CTL activity recovered from rat sponge grafts is of shorter duration and less intense. Assessment of the spontaneous .N = 0 production by mouse allograft infiltrating cells reveals a more delayed time course of production, paralleling the recovery of CTL activity from the graft. The in vitro spontaneous .N = 0 production by mouse allograft-infiltrating cells was greater than the production by syngeneic graft-infiltrating cells on all days tested. Exposure of allogeneic but not syngeneic graft infiltrating cells to the sensitizing alloantigen in vitro resulted in enhanced .N = 0 synthesis. In contrast, LPS stimulated .N = 0 production by both syngeneic and allogeneic graft cells on all days postgrafting. Culture of day-14 allograft infiltrating cells with alloantigen in the absence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of .N = 0 synthesis, resulted in elevated supernatant NO2- levels and decreased 3H-TdR uptake and CTL activity compared with cultures carried out in the presence of NMA. The supernatant NO2- levels, as well as the CTL activity and 3H-TdR incorporation of the cultured cells, was dependent on the concentration of NMA present, and these effects could be reversed by excess L-arginine. Thus, the species difference in .N = 0 synthesis (rat > mouse), observed by others, is evident in the sponge allograft model and may explain why CTL activity recovered from rat allografts is of shorter duration and less intense than that from the mouse allografts.

Bacterial translocation during graft-versus-host disease after small bowel transplantation is reduced following inhibition of inducible nitric oxide synthesis.

BACKGROUND: Increased nitric oxide (NO) production may contribute to intestinal barrier dysfunction and increased bacterial translocation (BT). Since BT may play a major role in graft-versus-host disease (GVHD) after small bowel transplantation (SBTx), we evaluated the role of NO production in GVHD after SBTX in the rat. METHODS: Using the standard model of semiallogeneic SBTx in the rat, we prepared three experimental groups. Recipients in group 1 received LBNF1-LBNF1 transplants and were treated with aminoguanidine (AG) (200 mg/kg), recipients in group 2 received Lewis-LBNF1 grafts and were injected with saline, and recipients in group 3 received Lewis-LBNF1 transplants and AG (200 mg/kg). Urine nitrite/nitrate levels were measured daily, and BT was determined by culturing peritoneal swabs, mesenteric lymph nodes, spleen, liver, and blood. RESULTS: In group 1 we detected indefinite survival with normal histology. In group 2 a survival of 10.5 +/- 1.1 days was reached, and the typical histological features of acute GVHD were observed. The animals in group 3 showed a mean survival of 14.8 +/- 0.6 days (P<0.02 compared with group 2) and the histological features of acute GVHD, although with a prolonged time course. Comparing NO production and BT between groups 2 and 3 we detected significantly reduced NO production on postoperative days 2-9 (P<0.03) and significantly decreased BT on postoperative days 3 and 9 (P<0.03). CONCLUSION: Inhibition of inducible NO synthesis with AG reduces NO production, decreases BT, and prolongs survival during GVHD after SBTx and therefore may be a useful addition to standard treatment protocols for GVHD.

Evidence that small bowel preservation causes primarily basement membrane and endothelial rather than epithelial cell injury.

The main site of injury induced during small bowel preservation is perceived to be the basement membrane and the endothelium of the highly vascularized mucosa, an aspect evaluated here in further detail. The effects of preservation were studied using a specific basement membrane stain (laminin antibody), an endothelial cell stain (factor 8 antibody) and standard histology. In addition, mucosal glutaminase activity reflecting enterocyte integrity was measured as monitor of the extent of preservation injury. Using a rat model, small bowel grafts were harvested, the vascular bed and bowel lumen were flushed, and the grafts were stored (4 degrees C) for 1, 6, 9, and 12 hr and transplanted into syngeneic hosts. After cold storage prior to transplantation, full-thickness small bowel biopsies were obtained for the various tissue preparations. Histologic evaluation at the end of the preservation period revealed separation of the villous epithelium from the lamina propria that increased with extending preservation time. Tissue staining with the laminin antibody disclosed progressive changes with increasing preservation intervals. Staining with the factor 8 antibody demonstrated also progressive changes, but failed to reflect in a gradual fashion increasing endothelial cell injury. Histologic injury became more pronounced after transplantation and reperfusion, then showing destruction of epithelial cells; the extent of injury correlated with the duration of preservation. Glutaminase activity was maintained after cold storage, indicating that the enterocytes remained intact during this period, but when assayed after reperfusion, glutaminase decreased with increasing preservation intervals and increasing histologic mucosal damage. We conclude that cold ischemic injury involves primarily the endothelium and the basement membrane, which progresses to global mucosal impairment with reperfusion.