Recipient morbidity after living and deceased donor liver transplantation: findings from the A2ALL Retrospective Cohort Study.

Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than two-fold higher when centers had performed 40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT.

Acyclovir triphosphate inhibits the diagnostic polymerase chain reaction for cytomegalovirus.

Immunocompromised patients are frequently treated with guanine analogs such as acyclovir and ganciclovir. Acyclovir triphosphate, the active intracellular metabolite of acyclovir, exerts its antiviral effect by inhibiting herpesviral DNA polymerases through premature chain termination. PCR has recently been used for early detection of cytomegalovirus. However, we and others have experienced false-negative results for cytomegalovirus-PCR in patients on both acyclovir and ganciclovir. The impact of these agents on PCR assay is unknown. In an attempt to investigate the role of guanosine analogs in these false-negative results, we exposed the DNA-PCR for murine beta-actin, a murine CMV IE gene sequence, and a human CMV IEA1 product, to phosphorylated acyclovir derivatives. Varying concentrations of acyclovir-5'-triphosphate (final: 70-6000 microM) in the reaction mix resulted in an absence of detectable product at or above 490-670 microM. Inhibition was not observed with up to 1400 microM acyclovir-monophosphate. Increasing the Taq concentration to 10 units/100 microL stopped the inhibition. Our data demonstrate that acyclovir-5'-triphosphate inhibits PCR amplification of various gene products in a concentration-dependent manner. Furthermore, this inhibition appears to be specifically directed against the Taq polymerase and can be completely reversed by higher concentrations of the enzyme. Thus, false-negative PCR results for a viral gene product in patients under prophylaxis/treatment with acyclovir could potentially be due to contamination by acyclovir triphosphate. Therefore, negative PCR results in these patients need be interpreted with caution.

Risk factors and impact of cytomegalovirus disease in simultaneous pancreas-kidney transplantation.

BACKGROUND: The relevance of cytomegalovirus (CMV) in simultaneous pancreas kidney (SPK) transplant recipients in the modern era of immunosuppression and antiviral therapeutics is largely unquantified. We sought to determine the risk factors of CMV disease and its impact on SPK transplant outcomes in recipients all receiving a consistent regime of maintenance immunosuppression and CMV prophylaxis. METHODS: This is a retrospective, single center study of 100 consecutive SPK transplant recipients. All received maintenance immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone. CMV prophylaxis consisted of a short course of parenteral gancyclovir followed by oral gancyclovir. Recipients at high-risk (D+/R-) for CMV also received CMV hyperimmune globulin. Multivariate analysis of risk factors for CMV disease and risk factors for adverse outcomes in SPK transplantation were determined. The effect of duration of prophylaxis on timing and severity of CMV disease in high-risk (D+/R-) SPK transplant recipients was also evaluated. RESULTS: The actual 1-year rate of CMV disease was 17.0% (12.0% noninvasive, 5.0% tissue invasive); and according to donor and recipient CMV serological status was: D-/R+: 0%; D-/R-: 2.8%; D+/R+: 25.6%; and D+/R-: 40.6%. Multivariate analysis showed transplantation of organs from a donor with positive CMV serology to be predictive of CMV disease with a relative risk of 63.37 (P=0.0052). In the high-risk (D+/R-) subgroup, the duration of prophylactic therapy delayed onset of CMV disease, but had minimal effect on severity. Invasive CMV disease was an independent predictor of mortality but did not decrease kidney or pancreas allograft survival. CONCLUSIONS: Outcomes of SPK transplantation have improved in the current era of modern immunosuppression, yet CMV remains an important pathogen. The serological status of the organ donor and the duration of CMV prophylaxis are predictive of who and when CMV disease may occur. Nevertheless, new strategies that reduce risk and severity of CMV disease are still needed.

The role of PCR in the diagnosis and management of CMV in solid organ recipients: what is the predictive value for the development of disease and should PCR be used to guide antiviral therapy?

Cytomegalovirus remains a significant source of morbidity and mortality in immunocompromised hosts. The increased sensitivity of molecular diagnostic techniques (PCR, antigenemia) has resulted in our ability to detect viral replication earlier in the posttransplant period, before the onset of symptoms. With the advent of effective antiviral therapy, "preemptive therapy," guided by sensitive, early and specific predictors of CMV disease, has become a realistic objective. Although multiple studies have analyzed the sensitivity and specificity of these tests, their predictive value for the development of disease has not been defined. The purpose of this study was to evaluate the predictive value of a positive CMV PCR in the setting of solid abdominal organ transplantation. A total of 476 PCR assays were performed on 134 transplant recipients (102 kidney, 19 kidney/pancreas, 11 liver, 2 other) either as protocol serial samples or as dictated by clinical events. All samples were concomitantly analyzed using standard virological assays for CMV including culture, shell vial, and serology. Patients with any CMV seropositive donor/recipient (D/R) combination received ganciclovir prophylaxis in conjunction with antilymphocyte induction for 14 days. No subsequent CMV prophylaxis was used. The positive predictive value was 55% in all seropositive donor/recipient combinations. The highest risk group (seronegative recipient of seropositive donor) showed the highest positive predictive value, whereas seropositive recipients of either seropositive or seronegative donors showed positive predictive values of 45% and 25%, respectively. Negative predictive value was 100% for all groups. Early detection of CMV infection has important implications for patient management, including preemptive therapy, which can be guided by PCR, especially in high risk (D+/R-) patients.

Gastric adenocarcinoma of Meckel's diverticulum as a cause of colonic obstruction.

A 45-year-old-female patient with no prior surgical history presented with bowel obstruction. At laparotomy, a bulky tumor arising from the ileum, which completely obstructed the sigmoid colon, was found. A left hemicolectomy followed by a transverse colostomy and a Hartman's pouch were performed. Pathological examination of the specimen revealed gastric adenocarcinoma arising from a Meckel's diverticulum in the ileum. Malignant transformation from a Meckel's diverticulum is an uncommon occurrence. This case illustrates that successful management of a symptomatic Meckel's diverticulum, even with malignant transformation, can be achieved by surgical resection.

Right lower quadrant abdominal pain due to appendicitis and an incarcerated spigelian hernia.

Spigelian hernias are uncommon and difficult to diagnose because of their location in the aponeurosis in the anterior abdominal wall. When they occur on the right side, the symptoms can include nonspecific abdominal pain mimicking appendicitis. We present an adult with right lower quadrant abdominal pain due to an incarcerated spigelian hernia and acute appendicitis. Early recognition and prompt surgical treatment were important to the successful treatment of our patient.

Intestinal volvulus following laparoscopic cholecystectomy.

The introduction of laparoscopic cholecystectomy has revolutionized the surgical management of biliary diseases. As the application of this procedure becomes more popular, a variety of associated complications have emerged. We present a rare case of a patient who developed an intestinal volvulus 3 days following laparoscopic cholecystectomy. The precipitating factors of this complication and review of literature are discussed.

Renal allograft outcome in recipients of positive-crossmatch combined liver-kidney transplantation.

BACKGROUND: Successful kidney transplantation despite positive crossmatch (+CXM) before transplantation is well recognized in combined liver-kidney transplant (CLKT) recipients. This is probably due to immunologic protection of the renal allograft (RA) conferred by the liver allograft. However, occurrences of antibody-mediated rejection and poor long-term RA outcome is also documented with +CXM CLKT recipients, suggesting that such immunologic protection may not be universal. METHODS: A total of 1,401 CLKT recipients with known status of pre-transplantation CXM were identified from the United Network for Organ Sharing registry from January 1, 1986, to December 31, 2006. Univariate analysis for significant differences in clinical variables and Kaplan-Meier estimate for patient and graft survivals were performed. The results were compared between positive and negative CXM groups. RESULTS: Pre-transplantation +CXM was seen in 17.3% (242/1401) of CLKT recipients studied. The demographic and clinical characteristics were similar between the groups, except for higher panel reactive antibody level and CXM positivity in female recipients. Outcome analysis showed higher RA rejection (19.3% vs 10.8%; P = .026) and increased hospital length of stay (37.3 ± 46.0 vs 28.8 ± 33.2 days; P = .028) in the +CXM group. RA survivals at 1, 3, and 5 years were 8%, 7%, and 6% lower in the +CXM group. The patient and liver allograft survivals were not different between the groups. CONCLUSIONS: In CLKT recipients with pre-transplantation +CXM, the immunologic protection of RA conferred by the liver allograft is less robust than previously perceived and may lead to higher rejection rate and poor RA outcome. This can be mitigated with routine pre-transplantation CXM.

Laparoscopic liver surgery: parenchymal transection using saline-enhanced electrosurgery.

Minimally invasive liver resection (MILR) has evolved considerably in the past decade. Safe hepatic parenchymal transection, has been one of the technical hurdles that has become evident during the growth of MILR. Advances in technology have now made safe liver transection a reality allowing resections of greater magnitude. In this review, the precoagulation approach is described in both methodology and technique. Using this method of liver transection, we have been able to perform MILR of all varieties and magnitudes, with favorable patient outcomes. A detailed description of one particular device will be highlighted to disseminate our experience and thus broaden the technical options for hepatobiliary surgeons wishing to offer their patients a minimally invasive therapy.

Laparoscopic-assisted right lobe donor hepatectomy.

The major impediment to a wider application of living donor hepatectomy, particularly of the right lobe, is its associated morbidity. The recent interest in a minimally invasive approach to liver surgery has raised the possibility of applying these techniques to living donor right lobectomy. Herein, we report the first case of a laparoscopic, hand-assisted living donor right hepatic lobectomy. We describe the technical aspects of the procedure, and discuss the rationale for considering this option. We propose that the procedure, as described, did not increase the operative risks of the procedure; instead, it decreased potential morbidity. We caution that this procedure should only be considered for select donors, and that only surgical teams familiar with both living donor hepatectomy and laparoscopic liver surgery should entertain this possibility.

Direct evidence using in situ polymerase chain reaction that the endothelial cell and T-lymphocyte harbor latent murine cytomegalovirus.

The latent viral genome, harbored indefinitely, threatens reactivation from its remote location. Although polymerase chain reaction (PCR) has detected the organs responsible for latency, it is not known whether latent cytomegalovirus (CMV) infection is maintained within organ-specific cells or ubiquitous elements such as macrophages, endothelial cells, or perhaps others. PCR lacks correlation with tissue structure. However, PCR-based in situ hybridization maintains cellular architecture while allowing the identification of the latently infected cells. Murine CMV (MCMV) nucleic acid sequences in organs of latently infected Balb/C mice were amplified by PCR incorporating digoxigenin-11-dUTP, holding the product DNA in situ (appropriate controls analyzed in parallel). Product DNA was then hybridized in situ with a biotinylated oligonucleotide probe for detection via streptavidin-alkaline phosphatase and light microscopy. Immunohistochemistry verified the positive cell types. Using this technique, we have shown directly in multiple organs of latently infected Balb/C mice including kidney (5/5), liver (5/5), and spleen (5/5) that the endothelial cell and/or T-lymphocyte harbor latent MCMV, whereas in uninfected animals, MCMV DNA was not detected. PCR-based in situ hybridization allows detection of the specific cell(s) harboring latent MCMV DNA while allowing conservation of cellular architecture.

Cellular localization of latent murine cytomegalovirus.

Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for harboring latent virus, in most cases, is not known. Using immunofluorescence and PCR-in situ hybridization (PISH), a technique which combines the sensitivity of PCR with the localization and specificity of in situ hybridization, we provide the first direct evidence that endothelial cells are a major site of murine cytomegalovirus (MCMV) DNA in latently infected animals. These findings are consistent with existing knowledge of the biological behavior of CMV, in particular the transmission of latent CMV by solid organ and bone marrow transplantation, in both human and animal models. In addition, we have localized MCMV DNA in the lung alveolar macrophage and in bone marrow cells. Our findings confirm that bone marrow-derived hematopoietic cells are a site of CMV latency and further suggest that bone marrow may be a reservoir of infected progeny capable of migrating into the circulation and establishing latency in various tissues. These findings provide clearly needed insight into the site of latent infection which is central to an understanding of the mechanisms of reactivation.

Pancreas transplantation at Northwestern University.

The collective advances made by many groups have significantly improved the results of pancreas transplantation. We have focused on the development of safe and effective immunotherapy, including a new protocol of rapid withdrawal of corticosteroids, the analysis of surgical technique of pancreas exocrine drainage on outcome and the role of SPK transplantation in patients with significant cardiovascular disease. We have found that multimodal immunotherapy including induction with tacrolimus-based maintenance combined with either MMF or sirolimus, with or without corticosteroids, resulted in excellent patient and graft survival rates with low rates of rejection. In this setting, enteric drainage was preferable to bladder drainage because of a lower rate of complications leading to hospital readmissions. Careful pretransplant screening for cardiovascular disease should be routinely performed for all SPK candidates. If successful coronary revascularization can be achieved, these patients can safely undergo SPK transplantation, with 5-year outcomes similar to those for recipients without coronary disease. Finally, we have observed that pancreas transplantation has an important ameliorating effect on hypertension that is independent of the method of pancreas exocrine drainage.