Inflammatory myofibroblastic tumours of the liver - a systematic review.

BACKGROUND: Hepatic inflammatory myofibroblastic tumours (HIMTs) are rare and poorly described in the literature. Most publications are single patient case reports and lack detailed reporting on characteristics, management, and outcomes. This systematic review aimed to assess the demography, clinical presentation, typical imaging features, histopathology, treatment, and outcomes of patients presenting with HIMTs. METHODS: A systematic literature search was performed in MEDLINE (PubMed), EMBASE (Scopus), JSTOR, Cochrane CENTRAL (Cochrane Library), and the databases included in the Web of Science for studies published between 1940 and 2023 on HIMTs, including its reported synonyms. Case series or cohort studies that reported on the management and outcomes of at least four patients with histologically confirmed HIMTs were included in the analysis. RESULTS: After screening 4553 publications, 22 articles including a total of 440 patients with confirmed HIMTs were eligible for inclusion. The average age was 53.4 years (range 42.0-65.0) with a male to female ratio of 1.7:1. Abdominal pain, discomfort, fever, and loss of weight were the most common presenting symptoms. Surgical resection is the standard of care for HIMTs and is associated with low mortality of 3.4% and low disease recurrence. CONCLUSION: HIMT is a disease more often affecting middle-aged males. The lesions are typically solitary with low recurrence after treatment. The relative roles of surgical versus medical treatment remain unclear. Differences in clinical presentation, histopathology, and treatment of HIMTs compared to inflammatory myofibroblastic tumour (IMT) at extrahepatic sites could challenge the current view of IMT as a single pathological entity.

Improved coating of pancreatic islets with regulatory T cells to create local immunosuppression by using the biotin-polyethylene glycol-succinimidyl valeric acid ester molecule.

BACKGROUND: We showed that T regulatory (Treg) cells can be attached to the surface of pancreatic islets providing local immunoprotection. Further optimization of the method can improve coating efficiency, which may prolong graft survival. In this study, we compared the effectiveness of two different molecules used for binding of the Tregs to the surface of pancreatic islets. Our aim was to increase the number of Treg cells attached to islets without compromising islets viability and function. METHODS: The cell surface of human Treg cells and pancreatic islets was modified using biotin-polyethylene glycol-N-hydroxylsuccinimide (biotin-PEG-NHS) or biotin-PEG-succinimidyl valeric acid ester (biotin-PEG-SVA). Then, islets were incubated with streptavidin as islet/Treg cells binding molecule. Treg cells were stained with CellTracker CM-DiL dye and visualized using a Laser Scanning Confocal Microscope. The number of Treg cells attached per islets surface area was analyzed by Imaris software. The effect of coating on islet functionality was determined using the glucose-stimulated insulin response (GSIR) assay. RESULTS: The coating procedure with biotin-PEG-SVA allowed for attaching 40% more Treg cells per 1 µm(2) of islet surface. Although viability was comparable, function of the islets after coating using the biotin-PEG-SVA molecule was better preserved than with NHS molecule. GSIR was 62% higher for islets coated with biotin-PEG-SVA compared to biotin-PEG-NHS. CONCLUSION: Coating of islets with Treg cells using biotin-PEG-SVA improves effectiveness with better preservation of the islet function. Improvement of the method of coating pancreatic islets with Treg cells could further facilitate the effectiveness of this novel immunoprotective approach and translation into clinical settings.

Donor height in combination with islet donor score improves pancreas donor selection for pancreatic islet isolation and transplantation.

To maximize the islet isolation yield for successful islet transplantation, the key task has been to identify an ideal pancreas donor. Since implementation of the islet donor score in donor selection, we have consistently obtained higher islet yields and transplantation rates. In this study, we tested whether assessing donor height as an independent variable in combination with the donor score could improve the pancreas donor selection. Donor and islet isolation information (n = 22) were collected and studied between 2011 and 2012. Pearson correlation analysis was used in statistical analysis. Donor height as an independent variable was significantly correlated to the weight of the pancreas, pre-Islet Equivalents (pre-IEQ), post-IEQ, and IDS (P < .05). When donor with height of 179 cm ± 3 was selected in combination with IDS > 80, the clinical islet transplantation rate reached 80%.

De novo sirolimus and reduced-dose tacrolimus versus standard-dose tacrolimus after liver transplantation: the 2000-2003 phase II prospective randomized trial.

We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose: 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone.

Transmission of human immunodeficiency virus and hepatitis C virus from an organ donor to four transplant recipients.

In 2007, a previously uninfected kidney transplant recipient tested positive for human immunodeficiency virus type 1 (HIV) and hepatitis C virus (HCV) infection. Clinical information of the organ donor and the recipients was collected by medical record review. Sera from recipients and donor were tested for serologic and nucleic acid-based markers of HIV and HCV infection, and isolates were compared for genetic relatedness. Routine donor serologic screening for HIV and HCV infection was negative; the donor's only known risk factor for HIV was having sex with another man. Four organs (two kidneys, liver and heart) were transplanted to four recipients. Nucleic acid testing (NAT) of donor sera and posttransplant sera from all recipients were positive for HIV and HCV. HIV nucleotide sequences were indistinguishable between the donor and four recipients, and HCV subgenomic sequences clustered closely together. Two patients subsequently died and the transplanted organs failed in the other two patients. This is the first recognized cotransmission of HIV and HCV from an organ donor to transplant recipients. Routine posttransplant HIV and HCV serological testing and NAT of recipients of organs from donors with suspected risk factors should be considered as routine practice.

Liver and vascularized posterior rectus sheath fascia composite tissue allotransplantation.

Abdominal wall closure in pediatric solid organ recipients may be confounded by donor size discrepancy and structural insults from previous surgery. Here we describe the novel use of vascularized donor abdominal wall posterior rectus sheath fascia, as a composite tissue allotransplant (CTA), to achieve abdominal wall closure in a liver and double kidney pediatric recipient who could not be closed primarily due to donor/recipient size mismatch. The posterior rectus sheath fascia was procured in continuity with the liver and falciform ligament. Blood supply was achieved using the single hepatic artery anastomosis as part of the standard liver transplantation procedure. Specimens of posterior rectus sheath fascia taken on postoperative days 3 and 30 showed no signs of acute rejection. The patient succumbed to an overwhelming fungal infection on day 51, with no signs of intraabdominal involvement. The patient received no additional immunosuppression in conjunction with the posterior rectus sheath fascia allotransplant.

Acute humoral rejection in an ABO compatible combined liver-kidney transplant--the kidney is not always protected.

Combined liver-kidney transplantation has become a common practice for the treatment of patients with concurrent end-stage renal disease and end-stage liver disease. Liver transplantation in the setting of multiorgan transplantation is thought to have a protective effect against humoral rejection even when a positive crossmatch is obtained prior to surgery. In most centers, a pre liver-kidney transplant crossmatch is rarely performed because of the known immunoprotective effect of the liver allograft. In this report, a case of acute humoral rejection in the kidney allograft after a combined liver-kidney transplant is described. Although humoral rejection was treated using plasmapheresis, intravenous immunoglobulin and rituximab, the kidney required 3 months to recover function and finally progressed to chronic allograft nephropathy. A heightened index of suspicion for acute humoral rejection of the renal allograft is necessary when performing combined liver-kidney transplants to highly sensitized patients due to previous organ transplants.

2007: the year of regulatory change.

INTRODUCTION: The two countries that performed the most organ transplants in 2006, the United States and China, initiated significant regulatory changes in 2007 that continue into 2008 and likely several more years. The purpose of this article is to highlight the reasons behind the regulatory initiatives, document the new regulations, and assess the impact thus far. METHODS: Review of US and Chinese governmental regulations emphasizing the underlying principles and impact. RESULTS: We evaluated the changes with respect to equity and transparency; understanding transplant policy; field strength; and informed consent. We found a number of similarities between the US and Chinese regulatory changes. The changes in the United States introduced new members into the team (independent donor advocates) and improved documentation, while China began the process of regulation by defining the process and identifying practices that are not allowed. CONCLUSIONS: We found a number of similarities between the regulatory changes in the United States and China. Both countries have made significant progress in attempting to improve the process for both donors and recipients. The United States is a more mature system, while China is attempting to move toward an international standard. In the short term, there may be decreased overall access to transplantation while transplant centers and policies adjust to the new regulations in both countries.

Entecavir therapy in a hepatitis B-related decompensated cirrhotic patient.

A 58-year-old Arab-American male with HBeAg-negative chronic hepatitis B (HBV), presented with decompensated cirrhosis and a high HBV DNA level. He responded to entecavir with a significant reduction in serum HBV DNA level after 15 weeks of therapy with entecavir. However, he developed a progressive rise in prothrombin time/international normalized ratio (PT/INR) and bilirubin and underwent liver transplantation after receiving 22 weeks of entecavir therapy. Furthermore, with the continued use of combination entecavir and hepatitis B immunoglobulins (HBIG), he showed improvement in his clinical status with a nondetectable serum HBV DNA level 12 weeks after transplantation. He continued to maintain nondetectable serum HBV DNA 2 years following transplantation. To the best of our knowledge, this is the first reported case of a patient with decompensated chronic HBV who responded to entecavir both before and after transplantation without showing any evidence of recurrent HBV. Larger clinical trials are recommended to compare both short-term and long-term efficacy using entecavir among nucleoside-naïve decompensated chronic HBV patients before and after liver transplantation.

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.

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.

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.

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.

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.

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.