Susceptibility of prosthetic biomaterials to infection.
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Animals↗
Biomedical subjects
J M Millis
Publications and source records attributed to J M Millis.
A novel tunneling method for long-term peritoneal dialysis.
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Catheterization↗
Islet isolation under cGMP conditions: replacing the coil.
INTRODUCTION: Clinical islet transplantation is increasingly regulated, with isolation standards defined under current good manufacturing practices (cGMPs). cGMP requires validation of equipment cleaning and sterilization. The automated process for islet isolation requires rapid thermal exchange during processing, manipulating a metal coil containing cellular product into and out of chilled/heated waterbaths. We recognize challenges of validating cleaning and sterilization of this coil and propose replacement with a disposable blood warming system. Our specific aims were to assess the system's ability to accommodate flow rates utilized during various phases of pancreatic digestion and to assess its efficiency of heat exchange and temperature control. METHODS: In a pancreas digestion circuit, heat exchange occurred via the coil in a digital water bath, or Warmflo blood warming bag in a digital warming unit. Temperature within the digestion chamber was assessed using an inserted thermocouple. Time to achieve 37 degrees C was measured for set heating element temperatures 38.5 degrees C to 41 degrees C. Circuit temperature maintenance characteristics were also recorded. RESULTS: The Warmflo bloodbag easily accommodated flows of 150 and 300 mL/min. At all set temperatures, the bag resulted in shorter or equivalent time to 37 degrees C than the coil. Maintenance of 37 degrees C was also equivalent. We have utilized this system for four human islet isolations with mean time to 37 degrees C of 5.5 minutes, without difference in digestion quality. CONCLUSIONS: Use of a disposable blood warming system in place of the coil during islet isolation provides adequate flow characteristics, heat exchange, and temperature control and may facilitate evolution of islet isolation toward cGMP compliance.
Cell Culture Techniques↗
The impact of donor factors on the outcomes following liver transplantation.
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Adult↗
Epidemiology and clinical consequences of vancomycin-resistant enterococci in liver transplant patients.
BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasingly important as pathogens in liver transplant patients. To guide control efforts, we conducted an epidemiological study of the frequency, source, and modes of transmission of VRE at our center. METHODS: During September 1998 through August 1999, we obtained weekly surveillance cultures from consenting liver transplant patients and surfaces in their rooms. Pooled handwash specimens from personnel also were obtained. Specimens were processed on selective media to detect VRE, and isolates were typed by pulsed field gel electrophoresis. Information was collected from patient records concerning in-hospital treatment and clinical course. RESULTS: Serial cultures were obtained during 33 admissions of 29 patients. VRE were detected in initial specimens from 6 admissions, and nosocomial acquisition of VRE occurred in 12 (44%) of the remaining 27 admissions. Seven different strain types of VRE were detected. The initial site of acquisition was stool in all cases; bile became culture-positive in only two patients. Overall, 16 (55%) of the 29 patients became colonized, usually after transplantation. VRE were detected in environmental cultures during 10 admissions and in 2 of 21 pooled handwashes. No statistically significant differences in clinical status or treatment were found when colonized patients were compared to noncolonized controls. The only VRE infection resulted from a choledochojejunostomy anastomotic leak. CONCLUSION: Alimentary tract colonization by VRE occurred commonly in liver transplant patients, probably by cross-transmission. The clinical consequences were modest in the patients studied, but colonized transplant patients provide a substantial reservoir for continued VRE transmission in hospitals.
Adult↗
Risk factors for chronic rejection after pediatric liver transplantation.
BACKGROUND: Chronic rejection is a major cause of graft failure and a frequent reason for retransplantation after pediatric liver transplantation. Identification of risk factors for chronic rejection in pediatric transplant recipients is vital to understanding the pathogenesis of chronic rejection and may help prevent further graft loss. METHODS: The study population consisted of 285 children with 385 liver transplants performed at University of Chicago between 1991 and 1999. Logistic regression analysis was used to evaluate risk factors for chronic rejection, including age, sex, race, type of graft (living related vs. cadaveric), native liver disease, acute rejection episodes, cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). RESULTS: The chronic rejection rate was significantly lower in recipients of living-related grafts than in recipients of cadaveric grafts (4% vs. 16%, P=0.001). African-American recipients had a significantly higher rate of chronic rejection than did Caucasian recipients (26% vs. 8%, P<0.001). Numbers of acute rejection episodes, transplantation for autoimmune disease, occurrence of PTLD, and CMV infection were also significant risk factors for chronic rejection. However, recipient age, gender, donor-recipient gender mismatch, and donor-recipient ethnicity mismatch were not associated with higher incidence of chronic rejection CONCLUSION: We have identified a number of risk factors for chronic rejection in a large group of pediatric liver allograft recipients. We believe that donor-recipient matching for gender or race is not likely to reduce the incidence of chronic rejection. The elucidation of the mechanisms by which living-related liver transplantation affords protection against chronic rejection may provide insight into the immunogenetics of chronic rejection and help prevent further graft loss.
Black or African American↗
Transplantation of liver grafts from living donors into adults--too much, too soon.
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Adult↗
Open cardiotomy for removal of migrating transjugular intrahepatic portosystemic shunt stent combined with liver transplantation.
BACKGROUND: Transjugular intrahepatic shunts are widely used for the management of variceal bleeding. Complications such as stent misplacement or migration may occur. METHODS: We describe the management of a transjugular intrahepatic shunts stent that migrated across the tricuspid valve in a patient with Child-Pugh category C cirrhosis. RESULTS: An attempt at percutaneous retrieval of the stent was unsuccessful. Due to the unacceptably high risk for mortality from open heart surgery with cardiopulmonary bypass in the setting of cirrhosis, stent removal was deferred until the time of orthotopic liver transplantation. The procedures were performed successfully, and the patient made a good recovery. CONCLUSION: Surgical stent extraction and valve repair can be performed safely along with orthotopic liver transplantation in carefully selected patients with end-stage liver disease.
Cardiac Surgical Procedures↗
De novo hepatitis with autoimmune antibodies and atypical histology: a rare cause of late graft dysfunction after pediatric liver transplantation.
BACKGROUND: Late graft dysfunction after orthotopic liver transplantation is commonly due to chronic rejection, recurrence of primary disease, sepsis, lympho-proliferative disease, or vascular or biliary complications. Herein we describe a subset of pediatric liver transplant patients in whom late graft dysfunction was associated with autoimmune markers, bile ductular proliferation, and portal infiltrates, which progress to fibrosis. This subset of patients has not been previously described. METHODS: Six of the 115 children followed for greater than 5 years after transplantation developed this unusual form of graft dysfunction. All children were on a low-dose single immunosuppressive therapy (mean trough cyclosporine concentration 89 microg/L) and had been tapered off steroids for a median duration of 1.5 year. Liver biopsies were performed in all children to evaluate the graft dysfunction, and the histologic findings were interpreted by an experienced hepato-pathologist. All patients were tested for antibodies to hepatitis C virus, hepatitis B surface antigen, and IgM antibodies to hepatitis A. Smooth muscle antibody, antinuclear antibody, and antibody to liver/kidney microsome type 1 were sought by indirect immunofluorescence. International Autoimmune Hepatitis Group scores were calculated. All patients underwent ultrasonography with doppler studies at the onset of graft dysfunction. Three patients with marked bile duct proliferation on histology had cholangiograms. RESULTS: Histology in all patients showed mononuclear cell infiltrates in the portal area with interface hepatitis, portal fibrosis, and ductular proliferation without duct damage or loss. All six patients had positive antinuclear antibody or smooth muscle antibody titers. Viral studies for hepatitis A, B, and C were negative in all patients. On the International Autoimmune Hepatitis Group scoring system, five patients had probable autoimmune hepatitis (score of 10-15) and one had definite autoimmune hepatitis (score > 15) at the onset of graft dysfunction. All were treated with azathioprine and prednisone similar to treatment for autoimmune hepatitis. However, despite aggressive treatment, four patients developed bridging portal fibrosis resulting in graft loss in two patients. CONCLUSION: This clinical constellation is associated with worse outcome then that previously described for pediatric patients with posttransplantation de novo autoimmune hepatitis. Further studies are needed to find an optimal treatment regimen for these patients.
Adolescent↗
Is any method of vascular control superior in hepatic resection of metastatic cancers? Longmire clamping, pringle maneuver, and total vascular isolation.
HYPOTHESIS: Although control of the hepatic vascular pedicle is commonly used during hepatic resection, the optimal method of vascular control continues to be debated. The utility of total or selective vascular isolation, pedicle inflow occlusion, or the absence of vascular isolation during minor and major hepatectomy needs to be examined. DESIGN: Retrospective review of hepatic resections performed for either isolated colorectal or noncolorectal hepatic metastases. SETTING: The University of Chicago Hospitals, Chicago, Ill, a tertiary-care referral center. PATIENTS: One hundred forty-one patients who underwent hepatic resection for isolated metastatic liver disease were identified through The University of Chicago Hospitals Tumor Registry. MAIN OUTCOME MEASURES: Intraoperative parameters, perioperative morbidity and mortality, and tumor recurrence. RESULTS: Four groups were compared with alternative methods of vascular management, including total vascular isolation, Longmire clamping, Pringle maneuver, or no vascular control. Tumor number and size were not significantly different between groups. Blood loss and transfusion requirements tended to be higher in the total vascular isolation group and were significantly higher compared with the Pringle group (P =.06) and the no vascular control group (P =.04), but this also correlated with a higher incidence of complexity of surgical resection. The highest incidence of postoperative complications occurred in the total vascular isolation group (P<.05). With similar permanent pathologic margins, the rates of intrahepatic recurrence were similar among all groups, with the no vascular control group having the lowest recurrence rate. CONCLUSIONS: All methods of vascular control appeared equivalent with respect to limiting blood loss and transfusion requirements while providing adequate surgical margins. The highest rates of blood requirements and complications were noted in the total vascular isolation group, which corresponded to the highest incidence of complex resections. The Longmire clamp group incurred the lowest incidence of complications and resulted in identical surgical margins. The application of vascular control is beneficial to surgeons during hepatic resection, but the method of control should be selected based on the location and complexity of resection required and preference of the individual surgeon.
Aged↗
Surgical management of benign tumors of the liver.
INTRODUCTION: Benign tumors of the liver are increasingly being diagnosed and continue to represent a management challenge. These lesions constitute a substantial component of hepatic neoplasms evaluated and resected at a tertiary referral center. We reviewed our experience with resection of benign liver lesions to clarify the safety and effectiveness of this treatment. METHODS: Between January 1996 and January 2000, 28 patients with benign hepatic lesions were identified from a cohort of 140 hepatic resection patients. Demographic characteristics, operative management, morbidity, mortality and follow-up were retrospectively analyzed. RESULTS: The mean age in our patients was 35 +/- 14, with 24/28 (86%) patients being female. Seven of the 24 woman (29%) at presentation were either pregnant or immediate postpartum. A history of OCP use was noted in 14/24 (58%) female patients. The most common presenting symptom was abdominal pain in 12/28 (43%). Resection for an undiagnosed mass occurred in 11/28 (39%) patients. The distribution of pathology was hemangioma 10/28 (35.7%), adenoma 8/28 (28.6%), hepatic cyst 5/28 (17.9%), hamartoma 2/28 (7.1%), and FNH 3/28 (10.7%). Average size of the tumor was 7.4 +/- 3.9 (range 2.5-15 cm) with a mean of 1.4 +/- 0.8 lesions (range 1-3) per patient. Tumors were evenly distributed between the right and left side while eight patients (29%) had bilobar tumors. Enucleation rather than anatomic resection was performed in 18/28 (64%) patients, with a mean blood loss of 457 +/- 532 cc (range 50-2200 cc). Blood transfusion was required in only 3/28 (10%) patients, while total vascular isolation was used in only a single patient undergoing an extended left hepatectomy. Mean length of stay was 6.8 +/- 3.2 d (range 3-14 d). Three complications (10.7%) were encountered: pulmonary embolus, ileus and non-operative bile leak. There were no mortalities in this series. Recurrence of tumor occurred in only one patient with a giant hepatic cyst managed laparoscopically. CONCLUSIONS: In our institution, the management of clinically relevant benign tumors of the liver comprises a significant proportion of our resectional practice (20%). Our data suggests that both enucleation and anatomically based resections can be performed safely with minimal blood loss and transfusion requirements. Resection of symptomatic lesions was highly effective in treating abdominal pain due to these benign tumors. We advocate resection of non-resolving hepatic adenomas, symptomatic lesions, or when malignancy cannot be excluded.
Adenoma↗
Combined liver and kidney transplantation in children.
BACKGROUND: Preexisting renal dysfunction has been reported to significantly increase the morbidity and mortality associated with orthotopic liver transplantation (OLT). OLT alone has been recommended for adults and children with end-stage liver disease and reversible causes of renal failure (i.e., hepatorenal syndrome), whereas combined liver and kidney transplantation (LKT) has been shown to be an effective treatment for adults with combined end-stage liver and kidney disease. The purpose of this study was to examine the role of LKT in children. METHODS: Between October of 1984 and 1997, 385 children less than 18 years of age underwent OLT at the University of Chicago. During this same time period 12 patients underwent LKT. Data were gathered by retrospective review of the patients medical records and by interviews conducted with the patients' families. RESULTS: Actuarial patient survival was comparable for children who underwent OLT alone and LKT (69% versus 67% at 5 years). All allograft losses in the LKT group were the result of patient death and occurred within the first 90 postoperative days. Factors associated with decreased patient survival included severity of illness as reflected by United Network of Organ Sharing status and LKT after failed OLT or cadaveric renal transplant. CONCLUSIONS: In children with concomitant endstage liver and kidney disease, LKT can be considered an effective therapeutic option in selected patients. Long-term patient survival in patients undergoing LKT is comparable to that of patients with normal renal function undergoing OLT alone.
Child↗
Initial presentation with stage IV colorectal cancer: how aggressive should we be?
HYPOTHESIS: The appropriate surgical treatment of patients with colorectal cancer who are found on initial presentation to have stage IV disease is controversial. With presumed limited life expectancy, the role of primary colon or rectal resection has been questioned, as has the utility of synchronous hepatic resection. DESIGN: A retrospective chart review. SETTING: The University of Chicago Hospitals, Chicago, Ill, a tertiary-care referral center. PATIENTS: One hundred twenty patients were identified through The University of Chicago Hospitals Tumor Registry whose initial presentation showed stage IV colorectal cancer and who underwent laparotomy. MAIN OUTCOME MEASURES: The primary end points of the study were perioperative morbidity and mortality and overall survival. RESULTS: Median survival and 5-year survival were 14.4 months and 10%, respectively. Survival was greater for patients younger than 65 years than for those who were aged 65 years or older (18.3 vs 9.8 months; P = .007). Carcinomatosis was associated with significantly decreased survival when compared with less extensive stage IV disease (6.7 vs 18.1 months; P<.001). Patients who underwent any form of resection of hepatic metastases achieved a survival advantage over those with unresectable liver lesions (median survival, 29.6 vs 10.2 months; P<.001). Overall, 27 patients (22.5%) developed postoperative complications. Seven patients (5.8%) died during the postoperative period. CONCLUSIONS: Age of 65 years or older, carcinomatosis, and extensive (bilobar) liver involvement are associated with decreased survival and increased postoperative morbidity and mortality and may negate any potential benefit patients derive from resection of the primary lesion. A substantial number of patients with synchronous hepatic metastases have protracted survival that justifies resection of the primary colorectal tumor at initial presentation. Despite the presence of stage IV disease, resection of the primary tumor and, when feasible, liver metastases is indicated.
Adult↗
Modern immunosuppression.
The current treatment of posttransplant lymphoproliferative disease (PTLD) includes prophylaxis at the time of transplant, decreasing or stopping immunosuppresion and initiation of antiviral therapy in patients with polymerase chain reaction or clinical evidence of PTLD, and judicial reintroduction of immunosuppression in patients who have cleared their PTLD and have begun to have rejection. The pharmacology, pharmacokinetics, notable side effects, and toxicities of the immunosuppressive agents are described in this article. At the conclusion of each section the author's current practice with these agents and treatment strategies are described.
Antibodies↗
Pulmonary complications following liver transplantation in pediatric patients.
The purpose of this study was to define the incidence and type of pulmonary complications experienced by children after orthotopic liver transplantation (OLT). The radiological records of all patients receiving OLT during a 3-yr period were reviewed to identify evidence of a pulmonary abnormality. Medical records were then reviewed to determine type, duration, therapy and outcome of pulmonary disorders. Potential risk factors for the development of persistent pleural effusions were also analyzed. One hundred and fifty-one pediatric liver transplantations were performed on 113 patients during this period. Pneumonia developed in 27 patients, including 11 proven bacterial, six presumed bacterial, six viral and four fungal cases. All three deaths related to pulmonary complications were in this group. Three patients developed mild pulmonary hemorrhages, and three developed pulmonary calcifications, which did not impair lung function. Sixteen patients developed paralysis of the right hemidiaphragm, four required diaphragm plication. Pleural effusions developed in 86 patients, 38 persisted longer than 7 days. Patients with persistent effusions were more likely to develop allograft rejection than patients with no persistent effusion (p < 0.01) by chi2 analysis. Seven patients required tracheostomy placement. Of these, four were successfully decannulated, two died from non-pulmonary complications and one is receiving home ventilator support. In conclusion, the majority of children experience at least one pulmonary complication after OLT, but mortality due to pulmonary disease is low in this population. Persistent pleural effusions may be a heralding sign of allograft rejection. Viral, bacterial and fungal pneumonia were the only pulmonary causes of death and only one patient in this series has had significant chronic lung disease.
Adolescent↗
Hepatic resection: effective treatment for primary and secondary tumors.
BACKGROUND: Hepatic resection is an accepted therapeutic modality for isolated colorectal metastases (CRM) and primary hepatobiliary cancers (PC). Controversy continues regarding the safety, efficacy, and appropriateness of resection for noncolorectal metastases (NCM). METHODS: A retrospective review of 167 resections in 160 patients was performed to evaluate the impact of demographics and perioperative data on survival and recurrence. Statistical analyses were performed by Student t test, analysis of variance, and Kaplan-Meier survival estimates. RESULTS: Resections were performed for CRM, 110 of 167 (66%), NCM, 31 of 167 (19%), and PC, 26 of 167 (15%). The interval from primary to metastases was significantly longer in the NCM group than the CRM group (34.7+/-45.1 vs. 18.7+/-23.7 months; P<.01). Mean number of lesions was not different between groups; however, NCM were larger than CRM (5.9+/-4.5 vs 4.5+/-2.9 cm; P<.05). Operative complications were significantly greater for PC (54%) versus CRM and NCM (21% and 19%, respectively; P<.01), although length of stay was similar between groups. Perioperative mortality was 2%. Actuarial survival at 1 year, 3 years, and 5 years was CRM 91%, 54%, and 40%, PC 75%, 60%, and 38%, and NCM 68%, 36%, and not available, respectively (CRM vs. NCM; P<.01 at 3 years). CONCLUSIONS: Hepatic resection for primary and secondary malignancy can be performed with minimal morbidity and mortality. Resection of NCM is associated with a lower overall survival compared with CRM and PC. The disease-free interval from resection of the primary to metastasectomy is prolonged and hepatic recurrence infrequent after resection in the NCM group. These results suggest that tumor biology is a critical determinant of outcome after hepatic resection of primary and secondary hepatic tumors.
Aged↗
Primary living-donor liver transplantation at the University of Chicago: technical aspects of the first 104 recipients.
OBJECTIVE: To evaluate the impact of technical modifications on living-donor liver transplants in children since their introduction in 1989. SUMMARY BACKGROUND DATA: Although more than 4,000 liver transplants are performed every year in the United States, only approximately 500 are performed in children. Living-donor liver transplantation has helped to alleviate the organ shortage for small children in need of liver transplantation. Few centers have amassed a sufficient number of cases to evaluate the impact of the different techniques used in pediatric living-donor liver transplantation. METHODS: From 1989 through 1997, 104 primary living-donor liver transplants were performed at the University of Chicago. Three phases of the living-donor liver transplant program can be defined based on the techniques of vascular reconstruction: phase 1, November 1989 to November 1994 (n = 78); phase 2, November 1994 to January 1996 (n = 6); and January 1996 to present (n = 20). The patients' charts were reviewed retrospectively. The incidence and type of vascular complications and patient and graft survival rates were analyzed. RESULTS: Although the demographics of the patients have not changed during the three phases of the living-donor liver transplant program, the outcomes have improved. Without the use of conduits, the incidence of portal vein complications has significantly decreased from 44% to 8%. The incidence of hepatic artery thrombosis has decreased from 22% to 0% with the use of microvascular techniques. The combined use of both techniques has led to a significant increase in graft survival, from 74% to 94%. CONCLUSIONS: The living-donor liver transplant recipient operation has undergone significant technical changes since its introduction in 1989. These changes have decreased the vascular complications associated with this type of graft. Avoiding the use of vascular conduits and performing microvascular hepatic artery anastomoses are the critical steps in improving graft survival.
Anastomosis, Surgical↗
Successful combined liver-heart transplantation in adults: report of three patients and review of the literature.
BACKGROUND: Three patients received liver/heart transplantation, and we report their successful outcome. METHODS: Two patients had alcoholic cirrhosis and dilated cardiomyopathy; one had cryptogenic liver disease and idiopathic cardiomyopathy. RESULTS: All patients had evidence of portal hypertension and coagulopathy. The cardiac transplants were performed first. Cardiopulmonary bypass was discontinued in favor of venovenous bypass, and liver transplantation was then performed. All patients developed acute tubular necrosis; two required a brief period of hemodialysis. There was only one episode of acute cellular rejection of the liver. Protocol endomyocardial biopsies in all three patients revealed no evidence of rejection. All patients are currently using low doses of immunosuppressive medications and have normal liver chemistry tests and cardiac function; two patients have mild renal insufficiency. CONCLUSION: In selected patients with severe cardiac dysfunction and advanced liver disease, liver/heart transplantation can be successfully performed even in the face of portal hypertension and coagulopathy.
Adult↗