Hepatic ischemia-reperfusion injury causes E-selectin upregulation.
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Biomedical subjects
Publications and source records attributed to G B Zibari.
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BACKGROUND: The rarity, delayed presentation, and diagnostic difficulty of small-bowel tumors prompted this study. STUDY DESIGN: Charts were reviewed retrospectively for 85 patients with 89 small-bowel tumors (22 primary malignant, 23 primary benign, and 44 metastatic) over a 10-year period (1986-1996) at Louisiana State University Medical Center-Shreveport and two affiliated hospitals in Shreveport. RESULTS: Of the primary malignant tumors, 10 carcinoids and 11 duodenal adenocarcinomas were identified. Most primary benign tumors were adenomatous or hyperplastic polyps, diagnosed by esophagogastroduodenoscopy. Metastatic tumors accounted for nearly 50% of all small-bowel tumors. Across all three tumor types, the most common presenting signs and symptoms were abdominal pain and nausea and vomiting. In addition, patients with benign tumors were more commonly presented with gastrointestinal hemorrhage, and those with metastatic tumors were more likely to present with obstruction. The mean interval from the onset of signs and symptoms to operation was 54 days for primary malignant tumors and 330 days for primary benign tumors. Esophagogastroduodenoscopy and computed tomography of the abdomen were occasionally helpful in diagnosis. Among the 22 primary malignant tumors, curative resections were performed in 11 patients (for 9 carcinoids and 2 adenocarcinomas) and palliative resections were performed in 10 patients (for 9 adenocarcinomas and 1 myxoliposarcoma). One patient had carcinomatosis from colon cancer and an incidentally discovered ileal carcinoid; this carcinoid was not included in this group of resections for primary malignant small-bowel tumors. All operations for 39 (of 44) patients with metastatic tumors were palliative. The remaining 5 (of 44) patients had metastatic duodenal cancer (confirmed by esophagogastroduodenoscopy or endoscopic retrograde cholangiopancreatography with biopsy) and did not undergo laparotomy. Surgical complications occurred more commonly with metastatic than with primary malignant tumors. Patients with primary malignant tumors had a 5-year survival rate of 36%. CONCLUSIONS: These findings demonstrate that small-bowel tumors are difficult to diagnose because of delayed presentation, nonspecific signs and symptoms, and lack of accurate diagnostic studies. If the overall survival of patients with small-bowel tumors is to be improved, clinicians must have a high index of suspicion and be willing to perform exploratory celiotomy early.
The medical records of 267 patients who had liver tumors, primary and metastatic, from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients (80%) had metastatic disease, and 54 patients (20%) had primary liver disease. Their clinical manifestations and laboratory values were evaluated as factors predictive of diagnosis and survival. There was a significant increase in the occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung, and pancreatic primaries were more commonly synchronous. Breast metastases were more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and alkaline phosphatase and decreased albumin were the most common liver test abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the majority of colon cancer patients. Eighty-one percent of patients with primary liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C. Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had resections, 38 (48%) were unresectable, and 4 (5%) underwent liver transplantation. The patients who underwent surgery had a 32 per cent 5-year survival rate compared to a 0 per cent 5-year survival in the patients who did not have surgery (p = 0.0001). The patients who had resections had a better survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years with p = 0.0008). The perioperative morbidity rate was 16 per cent, with lobectomies having the best rate and trisegmentectomies having the worst. Perioperative mortality rate was zero for all liver resections. Hepatic resection and, in selected patients, liver transplantation are the only two available therapeutic modalities that produce long-term survival with a possible cure in patients with primary and metastatic liver tumor.
Necrotizing fasciitis is an aggressive soft-tissue infection that in the past has carried a significant mortality rate. One of the most important determinants of outcome is recognition of the disease process. This is followed by aggressive resuscitation measures and radical debridement at the initial operation to control the infectious spread at the outset. The objective of this study is to help reveal the benefits of aggressive early surgical debridement in the treatment of necrotizing fasciitis. A retrospective review of the medical records of 68 patients between the years 1980 and 1996 with the diagnosis of necrotizing fasciitis was performed. The patients were assigned to two groups, Group A (21; 31%), who had delay in therapy or inadequate preliminary therapy and Group B (47; 69%), who underwent aggressive surgical debridement from the outset. Concomitant disease processes were noted. The medical records of 68 patients were studied. Age ranged from 13 to 67 (mean, 52) years of age. There were 38 (56%) females, 21 (64%) of the patients were African-American, 24 (73%) of the patients had concomitant disease processes, 29 (42%) of the patients had a history of tobacco use, 11 (16%) of the patients had a history of alcohol consumption, and 11 (16%) of the patients were obese. Mortality in Group A was 8 of 21 patients (38%). Mortality in Group B was 2 of 47 patients (4.2%). The difference in mortality was found to be statistically significant (P = 0.0007). Early recognition and expeditious initial wide excision and debridement along with appropriate antibiotic coverage and support of systemic effects of necrotizing fasciitis serve to decrease morbidity and mortality. We believe the above is an absolute necessity followed by frequent washing and minor debridement of the wound until granulating tissue is observed. This can then be followed by procedures to close/cover the surgical defect (i.e., split-thickness skin grafts or various coverage flaps).
Although predominantly a disease of older adults, colorectal cancer affects the younger population with an incidence of two to six per cent. It is thought to carry a less favorable prognosis in the young than in the general population. This may be due to advanced stage of the tumor at diagnosis. This study is composed of 37 patients, aged 40 and younger, treated over a 20-year period for colorectal cancer at Louisiana State University Medical Center-Shreveport and E. A. Conway Hospital. It was performed to investigate the incidence, stage at diagnosis, and prognosis of colorectal cancer in these young patients. The location of the primary tumor was fairly evenly distributed throughout the colon and rectum in this population. Pain, weight loss, rectal bleeding, and nausea and vomiting were the most common presenting symptoms. A family history of colon cancer or premalignant lesions were not risk factors in this study. Seventy per cent of all patients were treated with curative intent, and 42 per cent of these patients developed recurrent disease. The patients in this review presented with a higher incidence of advanced disease. Thirty-seven per cent of the lesions were Duke's C and 22 per cent were Duke's D, with poor 5-year survival (11% and 0%, respectively) when compared with national studies. The absolute 5-year survival for all young patients with colorectal cancer was 26 per cent (5 of 19 patients). It is important for the surgeon to be aware of the potential for colorectal cancer in young patients and to take an aggressive approach to the diagnosis and early treatment of the disease.
Cirrhosis of the liver results from a variety of mechanisms that cause progressive hepatic injury. It is the sixth leading cause of death in all patients between the ages of 35 and 55. This study attempts to correlate the morbidity and mortality of spontaneous bacterial peritonitis in liver failure patients to numerous etiologic and clinical variables. A retrospective review of 26 patients with spontaneous bacterial peritonitis associated with chronic liver disease was performed in a university hospital. Demographics (age and gender), clinical variables (etiology of liver failure, Child's classification, prior history of ascites, fever, abdominal pain, encephalopathy, and upper gastrointestinal hemorrhage), and laboratory variables (ascitic polymorphonuclearcyte count and cultures, serum albumin, bilirubin, creatinine, and prothrombin time) were studied. All of the patients had Child's C liver disease. Mortality rate was 46 per cent. Alcohol (46%) and hepatitis (30%) were the most common etiologies. Escherichia coli and Klebsiella pneumoniae were the most common culture isolates. All of the infections were monomicrobial. The only significant predictor of mortality (P < 0.05) in this study was the peritoneal fluid polymorphonuclear (PMN) cell count. PMN count >1000 PMN/mm3 was associated with a mortality of 88 per cent. Few patients with spontaneous bacterial peritonitis are ultimately transplanted.
BACKGROUND: At least some transplanted livers secrete soluble human leukocyte antigens (sHLA) of donor phenotype into the body fluids of recipients. The individuals in whom this phenomenon occurs are by definition serologic allogeneic chimeras. Because an allogeneic transplanted liver may induce tolerance to itself and other organs in animals of the donor strain, and because maintenance of a soluble antigen in the circulation of any animal in sufficient quantity for a sufficient period generally leads to tolerance, this phenomenon may be biologically important. This study was performed to determine how common this phenomenon is and whether it occurs after transplantation of organs other than the liver. METHODS: We studied 445 serum samples obtained from transplant recipients (liver, n=12; kidney, n=18; and heart, n=8) before and at various intervals after transplantation. All patients studied had allografts that had functioned for more than 1 year. We used an enzyme-linked immunosorbent assay to quantitate sHLA-A2 and sHLA-A1/A3/A11 (as a cross-reacting group). Donor and recipient combinations were selected in which measurable allotypes in donors were not present in recipients. In some instances, an additional allotype was present in a recipient but not in a donor. RESULTS: All liver transplant recipients had detectable donor sHLA in their serum samples after transplantation. In 72% of kidney and 50% of heart transplant recipients, donor sHLA was found persistently in serum samples obtained after transplantation. Interestingly, all heart transplant recipients of HLA-A3, but none of HLA-A2, had detectable donor sHLA in their serum samples, a finding that may be due to technical reasons. High and stable serum concentrations of donor sHLA characterize long-term stable allograft function. CONCLUSIONS: Donor sHLA is produced by all transplanted livers, most transplanted kidneys, and at least half of (but probably more) transplanted hearts. The hypothesis that donor sHLA may be tolerogenic to liver transplants can be expanded to include kidney and heart transplants.
Neutrophils are important in ischemia and reperfusion injury. Multiple factors may be responsible for the adhesion of granulocytes to endothelial cells. P-selectin is a carbohydrate-binding glycoprotein that is stored preformed in endothelial cells as Weibel-Palade bodies. This preformation implies a very early role of P-selectin in the leukocyte adhesion process. Previous studies of P-selectin have not quantified its expression. The purpose of this study is to quantitate the expression and time course of P-selectin in response to renal ischemia and reperfusion injury. P-selectin was measured in 34 C57BL-6 mice after 30 minutes of occlusive left renal ischemia followed by 20 minutes, 2, 5, 10, and 24 hours of reperfusion. This was also performed in control and sham laparotomy groups. P-selectin was quantified using a new double radiolabeled 125I/131I monoclonal antibody technique and reported as percent injected dose per gram of tissue. P-selectin expression peaked at 20 minutes, plateaued up to 5 hours, and fell at 10 hours. Additionally, genetically altered mice that do not express P-selectin showed no up regulation after 5 hours of reperfusion. Pathology results confirmed significant renal injury. Renal ischemia and reperfusion injury caused significant upregulation of P-selectin. Expression of P-selectin at the short reperfusion time of 20 minutes reinforces the premise that P-selectin is one of the earliest adhesion molecules expressed. This early peak is probably caused by the release of preformed P-selectin. The delineation of these mechanisms of injury may be important in understanding and preventing renal injury in transplantation, sepsis, and shock.
The role of vancomycin in the treatment of infected arteriovenous chronic dialysis access is well established. However, the role of preoperative vancomycin administration in preventing infection in newly placed, revised, or surgically thrombectomized grafts has not been determined. We performed a prospective randomized study to examine whether vancomycin prophylaxis can decrease the incidence of postoperative graft infections. Over a 5-year period, 206 patients undergoing 408 permanent vascular access procedures were randomized into two groups. Group 1 (206 procedures) received a single intravenous dose of 750 mg of vancomycin approximately 6 to 12 hours before vascular access placement procedures, while group 2 (202 procedures) did not. Patients were evaluated for access infection within the following 30 days and before use of the access for chronic dialysis. Access infection developed in two patients (1%) in group 1 and in 12 patients (6%) in group 2 (P = 0.006). All 14 infections occurred in upper extremity polytetrafluoroethylene grafts. We conclude that the use of preoperative single-dose intravenous vancomycin prophylaxis for hemodialysis vascular graft procedures reduces the risk of postoperative access infection.
In previous studies we reported a solid-phase, enzyme-linked immunoassay (ELISA) that can be used to quantitate the soluble fraction of human histocompatibility leukocyte class I antigens (S-HLA-I) and study their relevance in transplantation. In this study we determined the concentration and distribution of S-HLA-I in patients with end-stage liver disease (ESLD), as well as in liver transplant recipients. Sera were obtained from 51 patients with ESLD and 40 donor-recipient pairs. We analyzed the S-HLA-I in sera obtained from liver donors, as well as from liver transplant recipients (patients with ESLD), with sera from the latter obtained before and at various intervals up to 3 yr after transplantation. The results of the analyses justify the following conclusions: 1) Patients with ESLD had mean values of S-HLA-I (909 +/- 596 ng/ml) greater than those for the normal population (643 ng/ml) (P < 0.05); the S-HLA-I secretion decreased with increasing severity of liver disease. 2) Patients with tumors had mean S-HLA-I levels (399 ng/ml) significantly lower than those in patients with ESLD related to other causes. 3) In liver transplant recipients the S-HLA-I levels stabilized at approximately 1 month after transplant and remained relatively stable thereafter (mean level 950 +/- 536 ng/ml). The observed levels were also greater than those for the normal population (P < 0.05). 4) Preoperative and postoperative S-HLA-I values in liver transplant recipients demonstrated a biphasic distribution, dividing patients into high- and low-secretor groups. 5) During the post-transplant observation period, of these selected liver transplant recipients there was no difference between high- and low-secretor groups in the incidence of rejection (high, 70%; low, 67%), graft survival (high, 95%; low, 94%), or patient survival (high, 95%; low, 94%). 6) Measurement of the total amount of S-HLA-I, containing yet undefined ratios of both donor and recipient S-HLA-I, cannot be used to predict a state of tolerance in liver transplant recipients.
Acute necrotizing pancreatitis is a highly morbid and lethal condition. We performed a retrospective study of all patients admitted to Louisiana State University Medical Center between 1980 and 1995 with a diagnosis of pancreatitis (N = 617) and specifically examined those (N = 26) who developed acute necrotizing pancreatitis. During the period 1980 to 1989, there were 7 patients who progressed to acute necrotizing pancreatitis. Six of these seven patients died (mortality, 86%). These patients were managed with multiple operations for debridement and necrosectomy. The age ranged from 31 to 86 years in this group, with a mean of 58.5. The patients' total hospital days ranged from 2 to 125 days with a mean of 63.5 days. In 1989, we adopted an initial nonoperative approach to necrotizing pancreatitis and began using CT-guided catheter drainage for this condition. During this time period, 19 patients have progressed to necrotizing pancreatitis. The range of hospital days was from 13 to 90 days, with a mean of 43.8 days. There were 2 deaths in this last group, resulting in a mortality rate of 10.5 per cent. All of these patients were treated nonoperatively in the acute phase of their illness. Two patients (15.8%) subsequently underwent laparotomy and drainage when the collections were not amenable to CT-guided drainage. Morbidity in this population approached 70 per cent; however, the mortality was only 10 per cent compared to 86 per cent in the previous group. Although nonoperative therapy has its associated morbidity, and although we understand the controversy surrounding the management of this condition, it appears at least in this population to have much less mortality than those who were treated operatively in the acute phase.
Transjugular intrahepatic portosystemic shunts (TIPS) are being used increasingly for complications of portal hypertension, including active and recurrent variceal hemorrhage and intractable ascites, as well as for portal decompression in patients awaiting orthotopic liver transplantation. We reviewed the initial 2-year experience with TIPS at Louisiana State University Medical Center-Shreveport and Willis-Knighton Medical Center, Shreveport, Louisiana, which involved 31 patients. Clinical findings (with some patients having more than one finding) revealed that 16 per cent (five) of the patients had active hemorrhage; 61 per cent (19), multiple episodes of (recurrent) variceal hemorrhage; and 48 per cent (15), ascites. The mean follow-up period was 6.2 months, with a patient mortality of 13 per cent. Results showed that in 87 per cent (27 of 31) of patients the TIPS procedure was successfully placed. There was 100 per cent control of active variceal hemorrhage (five patients) and ascites (12 patients; excludes three patients who died). Rebleeding occurred in 18 per cent (four of 22) of patients, all related to stenosis or occlusion of the TIPS. The overall incidence of occlusion and stenosis was 11 per cent and 22 per cent, respectively. Seventy-seven per cent (seven of nine) of the patients experiencing the latter complications underwent successful angioplasty or revision of their TIPS. The results of our experience indicate that TIPS placement can be performed successfully with low procedural morbidity. The procedure is effective in controlling active variceal hemorrhage refractory to endoscopic sclerotherapy. The use of TIPS may be particularly beneficial for patients who are either awaiting liver transplantation or poor candidates for surgical shunt procedures. TIPS may not be a long-term solution for patients with portal hypertension, given the current rates of occlusion and stenosis.
Anti-lymphocytes induction therapy in renal transplants remains controversial relative to efficacy and cost benefit. It has been suggested that shortening the duration of induction therapy from 14 to 7 d would provide adequate efficacy at less cost. Our objective was to compare the efficacy and complications of short (7 d or less, group A) versus standard (14 d or more, group B) duration of OKT3 induction therapy in renal allograft recipients. We performed a retrospective review of all renal allografts performed between July 1989 and September 1994. Two groups were identified based on the duration of OKT3 induction therapy. There were no significant differences between group A or B in the distribution of age, sex, race, degree of HLA matching, and etiology or renal failure. Patients in group B experienced fewer rejections at 3 and 12 months (p = 0.0236 and p = 0.0065, respectively) as well as fewer viral infections during the first year of follow-up (p = 0.0435). No difference on the mean number of bacterial or fungal infections existed between the two groups. There were no statistically significant differences in patient or graft survival, although patients in group B had a tendency towards increased 1-yr graft survival.
UNLABELLED: Orthotopic liver transplantation (OLT) for individuals with alcoholic liver disease (ALD) remains controversial. This review was designed to evaluate the survival, recidivism, and rehabilitation of the alcoholic liver transplant recipient in a single transplant center. METHODS: Between 10/86 and 11/92 203 liver transplants were performed in 179 patients. In 42 patients (23%) the primary etiologic diagnosis was ALD (36 males, 6 females, median age 47 yr). All ALD patients were evaluated preoperatively by social service, psychiatry, and medical psychology, in addition to hepatology and transplant surgery. A minimum abstinence period of 3-6 months was encouraged, although exceptions were made for cases of extreme medical urgency in which a good prognosis for abstinence was predicted. RESULTS: In OLT recipients with ALD, actuarial survival at 1, 2, and 3 yr was 74%, 71%, and 71%, respectively, compared to 71%, 71%, and 69% for all OLT recipients. One- and two-year survival was 85% in the most recently transplanted 86 patients, 20 of whom (23%) had ALD with 1- and 2-yr survival of 84% (N.S.). Recidivism was monitored postoperatively by interviews with the patient and family, supplemented by random urine and serum toxicology. Of the 29 survivors, 2 (7%) returned temporarily to alcohol use but are presently abstinent. Although none of the ALD patients in this study was able to work prior to OLT, 76% of the survivors at least 4 months post-transplantation were employed. CONCLUSIONS: Although our experience is small, our results suggest that OLT is appropriate therapy for carefully selected patients with end-stage liver failure due to ALD. The multi-disciplinary approach to preoperative evaluation of the alcoholic liver transplant candidate is effective in determining those patients committed to abstinence after a successful transplant.
From 1981 to 1986 a total of 499 operations were performed for permanent hemodialysis vascular access in 230 patients. At least 1 year's follow-up was achieved in all cases. This series is divided into 326 primary procedures and 173 secondary procedures. Of the primary procedures, there were 160 autogenous fistulas and 166 expanded polytetrafluoroethylene (PTFE) fistulas. The 156 secondary procedures consisted of 124 thrombectomies, 20 repairs of pseudoaneurysm, 12 fistula ligations, and 17 fistula excisions. The infectious complication rate (29/482) was 6%. Mean length of patency was 3.1 years for autogenous wrist fistula, 2.6 years for elbow fistula, 1.9 years for forearm loop PTFE, 2.1 years for straight forearm PTFE, 1.6 years for femoral popliteal PTFE, and 1.4 years for femoral arteriovenous loop PTFE. A vascular steal syndrome occurred in 8% of patients with autogenous elbow fistulas (4/48), compared with 1.7% (2/112) of patients with wrist fistulas and 1.8% (3/166) of those with PTFE fistulas. All infected fistulas required excision, and all fistulas associated with the steal syndrome required ligation. Use of PTFE to construct permanent hemodialysis vascular access has a significantly higher incidence of thrombosis, infection, pseudoaneurysm formation, and limb loss (p less than 0.01 for all complications) and a significantly lower mean length of patency (p less than 0.0001) when compared with autogenous fistulas. Age, sex, hypertension, diabetes mellitus, and the use of perioperative antibiotics were not found to be related significantly to access complications.