'Burn and Push' technique: A novel robotic liver parenchymal transection technique.

BACKGROUND: Liver parenchymal transection during robotic liver resection (RLR) remains a significant challenge due to the limited range of specialised instruments. This study introduces our 'Burn and Push' technique as a novel approach to address these challenges. METHODS: A retrospective analysis was conducted on 20 patients who underwent RLR using the 'Burn and Push' technique at Virginia Commonwealth University Health System from November 2021 to August 2023. The study evaluated peri- and post-operative outcomes. RESULTS: The median operation time was 241.5 min (range, 90-620 min), and the median blood loss was 100 mL (range, 10-600 mL). Major complications occurred in one case, with no instances of postoperative bleeding, bile leak, or liver failure. CONCLUSIONS: The 'Burn and Push' technique is a viable and efficient alternative for liver parenchymal transection in RLR. Further research with larger sample sizes and consideration of the learning curve is necessary to validate these findings.

Domino Liver Transplantation for Unresectable Colon Cancer Liver Metastasis From a Donor With Heterozygous Familial Hyperlipidemia: A Case Report.

Liver transplantation (LT) is a potential curative treatment for unresectable colorectal cancer liver metastasis (CRLM). Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. Liver transplantation is offered for selected cases, and an explanted liver can be used as a domino graft. We report the first report of domino LT for unresectable CRLM using a liver from a patient with heterozygous FH. The domino donor was a 30-year-old female with a history of heterozygous FH. She had failed medical therapies for FH, including plasmapheresis; therefore, she underwent living donor LT as a treatment for FH. The explanted liver was transplanted to the domino recipient. She has been doing well with normal LDL-C levels. The domino recipient was a 44-year-old female with a history of stage 4 sigmoid cancer with liver metastases, for which she underwent laparoscopic sigmoid colectomy and right hepatectomy. She developed unresectable lesions in the remnant left lobe, which were controlled well with chemotherapy; therefore, she underwent domino LT. She is doing well without recurrence at the 31-month follow-up. Domino LT from a donor with heterozygous FH is feasible for strictly selected patients with unresectable CRLM.

Liver transplantation for post-COVID-19 cholangiopathy: A case series.

BACKGROUND: Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS: Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS: At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS: Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.

Robotic hepatectomy and cholecystectomy in the management of intraductal papillary mucinous neoplasm of the biliary tract: A case report and literature review.

BACKGROUND: In the Western Hemisphere, Intraductal papillary mucinous neoplasm of the biliary tract (IPMN-B) is a rare lesion with uncertain aetiology. This report outlines a scarcely documented instance of IPMN-B treated using robotic hepatectomy and cholecystectomy supplemented with intraoperative imagery aimed at informing future robotic procedures. METHODS: A healthy person with acute cholangitis symptoms underwent diagnostic imaging followed by successful robotic hepatectomy and cholecystectomy. Pathological examination confirmed IPMN-B. RESULTS: The patient was consulted regarding the proposed procedure of robotic left hepatectomy, cholecystectomy, and potential hepaticojejunostomy, to which she provided consent. Subsequent surgical intervention resulted in clear margins for malignancy, and the patient recovered without complications. CONCLUSIONS: This case emphasises the importance of early diagnosis and intervention in managing IPMN. The use of a robotic approach, specifically through robotic left hepatectomy combined with cholecystectomy, offers minimally invasive surgery that provides exceptional visualisation and precise control.

Single incision simultaneous liver kidney transplantation: Feasibility and outcomes.

BACKGROUND: Traditionally, simultaneous liver kidney transplantation (SLK) has been performed using a subcostal incision for the liver allograft and a lower abdominal incision for kidney transplantation (dual incision, DI). At our institution, we performed SLK using a single subcostal incision (SI). The aim of this study was to report the outcomes of single versus dual incisions for SLK. METHODS: A retrospective cohort study of consecutive SLK procedures performed at our center from January 2015 to April 2021 was performed. The demographic characteristics, complications, intraoperative findings, and complications after SI and DI were statistically compared. RESULTS: A total 37 SLK were performed (19 DI and 18 SI). The age and indications for transplantation were comparable between the two groups. Patient in SI group had significantly higher MELD score (27.0 ± 1.5 vs. 31.7 ± 1.5, p = .038). The cold ischemic time of kidney transplantation (599 ± 26 min vs. 447 ± 27 min, p < .001) and the total surgical time (508 ± 21 min vs. 423 ± 22 min, p = .008) were significantly shorter in the SI group. The incidence of complications and post-transplant kidney function was comparable between the groups. A slightly higher incidence of surgical site complications was noted in the DI group without any statistically significance (p = .178). CONCLUSIONS: Single-subcostal incision SLK is technically feasible and has comparable outcomes to dual-incision SLK. SI was associated with shorter cold ischemic time for kidney transplant, as well as shorter overall operative time.

Transplant Hepatectomy With Portacaval Shunt and MARS Therapy for Perioperative Catastrophe: A Series of Four Liver Transplant Cases.

Increased worldwide focus on maximal donor utilization and transplantation of patients once considered too ill to survive liver transplantation may increase the otherwise rare frequency of catastrophic graft failure. Although the deleterious effects of an acutely failing allograft have been established for decades, the optimal strategy in this patient population in the perioperative period remains ill-defined. METHODS: A retrospective review of all liver transplant recipients with perioperative failure leading to transplant hepatectomy between January 1, 2014 and June 30, 2017 was performed. All patients were supported with MARS therapy while awaiting retransplantation. RESULTS: Four patients experienced catastrophic graft failure from massive exsanguination and liver fracture (1), portal vein and hepatic artery thrombosis (1), idiopathic necrosis (1), and necrosis from inadequate donor flushing/primary nonfunction (1). All patients improved following transplant hepatectomy with portacaval shunting. Patients were supported with intubation, vasopressors, renal replacement therapy, and Molecular Adsorbent Recirculating System therapy. All patients underwent retransplantation after a mean anhepatic phase of 48.8 (± 5.13) h. Survival to discharge was 75%. CONCLUSIONS: Although catastrophic liver failure is highly challenging, acceptable outcomes can be achieved with timely hepatectomy with portacaval shunt and retransplantation, particularly in patients supported with the Molecular Adsorbent Recirculating System device.

Management of hepatic artery aneurysm: A case series.

Hepatic artery aneurysms are rare, but their diagnosis is important because of high mortality and complications. Common risk factors for developing these aneurysms include hypertension, vascular disease, pancreatitis, diabetes, tobacco use, autoimmune diseases, and previous transplantation. Frequent imaging for trauma and tumor surveillance has increased the incidence of naive hepatic aneurysms. These aneurysms can be difficult to manage, and it can be challenging to decide the correct treatment modality for the patient. Hereby, we present four cases of hepatic artery aneurysm and discuss various treatment options. Patient 1 suffered from a proper and right hepatic artery aneurysm discovered incidentally; repaired with an endovascular intervention later complicated by an endoleak which was further managed by another stenting. Patient 2 had a common hepatic artery aneurysm followed with serial imaging without any intervention. Patient 3 had a hepatic artery aneurysm and liver mass diagnosed concurrently. The patient underwent an open surgical repair of his aneurysm with graft and liver resection which was complicated later with rupture of aneurysm followed by surgical bypass repair. Patient 4 suffered from a large hepatic artery aneurysm causing bile duct compression. Her aneurysm was repaired open with splenic artery grafting. Patients were managed from careful observation to surgery with different outcomes.

Use of HCV-Positive Livers in HCV-Negative Recipients.

INTRODUCTION: There are only limited data on the survival outcomes after transplanting HCV RNA-positive liver into HCV RNA-negative recipients. The objective of our study was to determine whether there were graft and patient survival differences when HCV-negative patients received HCV RNA (nucleic acid amplification testing [NAT] positive)-positive liver grafts. METHODS: We queried the United Network for Organ Sharing data sets from January 2014 to December 2018, and recipients (N = 24,724) were stratified into 6 groups based on the status of HCV antibody and RNA of recipients and donors. The Cox proportional hazard regression was used to estimate the relationship between groups and 1-year post-LT graft or patient survival. RESULTS: During the study period, 1,358 recipients received NAT-positive liver grafts. Two hundred ten of the recipients were HCV negative. During the same period, 707 HCV antibody-positive but NAT-negative grafts were transplanted into 516 HCV-positive and 191 HCV-negative recipients. There were no differences in survival in HCV-positive recipients whether they received NAT-positive grafts (n = 1,148) or HCV antibody-negative/NAT-negative grafts (n = 6,321). Recipients of grafts from HCV antibody-positive/NAT-negative donors had similar survival whether recipients were HCV-negative patients (n = 191) or HCV-positive patients (n = 516), and their survival probabilities were similar to those of HCV-negative recipients (n = 6,321) receiving grafts from HCV antibody-negative/NAT-negative donors. Patient survival was lower (P = 0.049) when HCV-negative recipients (n = 210) received NAT-positive grafts compared with HCV-positive patients (n = 1,148) receiving NAT-positive grafts; however, when adjusted for recipient and donor characteristics, the difference was not significant. DISCUSSION: HCV-negative recipients receiving HCV-positive liver grafts (NAT positive) have excellent 1-year survival outcomes.

Echo is a good, not perfect, measure of cardiac output in critically ill surgical patients.

BACKGROUND: Compared with a pulmonary artery catheter (PAC), transthoracic echocardiography (TTE) has been shown to have good agreement in cardiac output (CO) measurement in nonsurgical populations. Our hypothesis is that the feasibility and accuracy of CO measured by TTE (CO-TTE), relative to CO measured by PAC thermodilution (CO-PAC), is different in surgical intensive care unit patients (SP) and nonsurgical patients (NSP). METHODS: Surgical patients with PAC for hemodynamic monitoring and NSP undergoing right heart catheterization were prospectively enrolled. Cardiac output was measured by CO-PAC and CO-TTE. Pearson coefficients were used to assess correlation. Bland-Altman analysis was used to determine agreement. RESULTS: Over 18 months, 84 patients were enrolled (51 SP, 33 NSP). Cardiac output TTE could be measured in 65% (33/51) of SP versus 79% (26/33) of NSP; p = 0.17. Inability to measure the left ventricular outflow tract diameter was the primary reason for failure in both groups; 94% (17/18) in SP versus 86% (6/7) NSP; p = 0.47. Velocity time integral could be measured in all patients. In both groups, correlation between PAC and TTE measurement was strong; SP (r = 0.76; p < 0.0001), NSP (r = 0.86; p < 0.0001). Bland-Altman analysis demonstrated bias of -0.1 L/min, limits of agreement of -2.5 and +2.3 L/min, percentage error (PE) of 40% for SP, and bias of +0.4 L/min, limits of agreement of -1.8 and +2.5 L/min, and PE of 40% for NSP. CONCLUSION: There was strong correlation and moderate agreement between TTE and PAC in both SP and NSP. In both patient populations, inability to measure the left ventricular outflow tract diameter was a limiting factor. LEVEL OF EVIDENCE: Diagnostic tests or criteria, level III.

Extracorporeal membrane oxygenation support following liver transplantation-A case series.

BACKGROUND: Postoperative severe cardiopulmonary failure carries a high rate of mortality. Extracorporeal membrane oxygenation (ECMO) can be used as a salvage therapy when conventional therapies fail. METHODS: We retrospectively reviewed our experience with ECMO support in the early postoperative period after liver transplant between September 2011 and May 2016. RESULTS: Out of 537 liver transplants performed at our institution, seven patients required ECMO support with a median age of 52 and a median MELD score of 28. Veno-venous ECMO was used in four patients with severe respiratory failure while the rest required veno-arterial ECMO for circulatory failure. The median time from transplant to cannulation was 3 days with a median duration of ECMO support of 7 days. All patients except one were successfully decannulated. The median hospital length of stay was 58 days with an in-hospital mortality of 28.6%. CONCLUSION: Extracorporeal membrane oxygenation can be considered a viable rescue therapy in the setting of severe postoperative cardiopulmonary failure. Extracorporeal membrane oxygenation therapy was successful in saving patients who were otherwise unsalvageable.

Hepatic Artery Pseudoaneurysm in the Liver Transplant Recipient: A Case Series.

INTRODUCTION: Hepatic artery pseudoaneurysm is a rare and potentially fatal complication of liver transplantation with a reported incidence of 0.3-2.6% and associated mortality approaching 75%. Clinical presentation typically includes sudden hypotension, gastrointestinal bleed or abnormal liver function tests within two months of transplantation. We report a series of four cases of hepatic artery pseudoaneurysm in adult liver transplant recipients with the goal of identifying factors that may aid in early diagnosis, prior to the development of life threatening complications. METHODS: A retrospective chart review at a high volume transplant center revealed 4 cases of hepatic artery pseudoaneurysm among 553 liver transplants (Incidence 0.72%) between March 2013 and March 2017. RESULTS: Two of the four patients died immediately after intervention, one patient survived an additional 151 days prior to death from an unrelated condition and one patient survived at two years follow up. All cases utilized multiple imaging modalities that failed to identify the pseudoaneurysm prior to diagnosis with computed tomography angiography (CTA). Two cases had culture proven preoperative intrabdominal infections, while the remaining two cases manifested a perioperative course highly suspicious for infection (retransplant for hepatic necrosis after hepatic artery thrombosis and infected appearing vessel at reoperation, respectively). Three of the four cases either had a delayed biliary anastomosis or development of a bile leak, leading to contamination of the abdomen with bile. Additionally, three of the four cases demonstrated at least one episode of hypotension with acute anemia at least 5 days prior to diagnosis of the hepatic artery pseudoaneurysm. CONCLUSIONS: Recognition of several clinical features may increase the early identification of hepatic artery pseudoaneurysm in liver transplant recipients. These include culture proven intrabdominal infection or high clinical suspicion for infection, complicated surgical course resulting either in delayed performance of biliary anastomosis or a biliary leak, and an episode of hypotension with acute anemia. In combination, the presence of these characteristics can lead the clinician to investigate with appropriate imaging prior to the onset of life threatening complications requiring emergent intervention. This may lead to increased survival in patients with this life threatening complication.

Postoperative Elevated Resistive Indices Do Not Predict Hepatic Artery Thrombosis in Extended Criteria Donor Livers.

Postoperative transplant liver ultrasounds were analyzed in standard criteria donor (SCD), extended criteria donor (ECD), and donation after cardiac death (DCD) liver allografts to determine if elevated resistive indices (RIs) are consistently present and if they are pathological. Postoperative transplant liver ultrasounds were reviewed from 115 consecutive patients. Hepatic arterial RIs were stratified based on the type of donor: DCD, macrosteatosis (>30%), or standard criteria. In all patients with elevated RI, subsequent ultrasounds were reviewed to demonstrate RI normalization. The mean RI for all 115 patients was 0.64, DCD was 0.67, macrosteatosis was 0.81, and SCD was 0.61 ( p = 0.033). The RI on subsequent liver ultrasounds for DCD and macrosteatosis normalized without any intervention. There were no incidences of early hepatic artery thrombosis (HAT) observed in the cohort. Hepatic arterial RI in ECDs and DCDs are elevated in the immediate postoperative period but are not predictive of HAT. It represents interparenchymal graft stiffness and overall graft edema rather than an impending technical complication. The results of our study do not support the routine use of anticoagulation or routine investigation with computed tomography angiography for elevated RIs as these findings are self-limiting and normalize over a short period of time. We hope that this information helps guide the clinical management of liver transplant patients from expanded criteria donors.

Resolution of donor non-alcoholic fatty liver disease following liver transplantation.

INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS: Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. RESULTS: The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. CONCLUSIONS: High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets.

Deep Vein Thrombosis and Pulmonary Embolism in Liver Transplant Patients: Risks and Prevention.

UNLABELLED: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are surgical complications estimated to occur in 5% to 10% of patients. There are limited data regarding DVT/PE in the early postoperative period in liver transplant patients. The aim of this study is to determine risk factors that influence the incidence of DVT/PE and the effectiveness of prophylaxis. METHODS: We reviewed the records of 999 patients who underwent initial liver transplant between January 2000 and June 2012 at Henry Ford Hospital. In 2011, a standardized prophylactic regimen using subcutaneous (SQ) heparin was initiated. All patients that developed either upper/lower extremity DVT or PE within the first 30 days of transplant formed the cohort of this study. RESULTS: On multivariate analysis, only peripherally inserted central catheter (PICC) placement and SQ heparin were associated with DVT/PE. In patients receiving heparin, 3 (1.0%) had DVT/PE versus 25 (3.5%) who did not receive heparin (P = 0.03). Sixteen (6.9%) patients that had a PICC developed DVT/PE compared with 12 (1.6%) patients without a PICC (P < 0.001). In the heparin group, DVT/PE with PICC was reduced to 3 (3.0%) versus 13 (9.9%) in those with a PICC and did not receive heparin (P = 0.03). Mean time from transplant to DVT/PE diagnosis was 12.3 days. Length of hospitalization was significantly longer in patients who developed DVT/PE (18.5 vs 10.0 days, P < 0.001). CONCLUSIONS: In this study, we demonstrated that PICC placement significantly increases the likelihood of DVT/PE in liver transplant recipients. Prophylactic SQ heparin effectively reduced DVT/PE events in this patient population.

Intrahepatic Cholangiocarcinoma in the Liver Explant After Liver Transplantation: Histological Differentiation and Prognosis.

BACKGROUND: The aim of this study was to evaluate the outcome of patients with intrahepatic cholangiocarcinoma (ICCA) incidentally found in the explanted liver after liver transplantation. MATERIAL AND METHODS: We retrospectively reviewed 1188 recipients undergoing liver transplantation from August 2003 to August 2014; 13 patients were found to have ICCA (1.1%). Recurrence-free survival (RFS) rate was compared between ICCA patients and the matched cohort of 39 patients with hepatocellular carcinoma (HCC). We also investigate the relevance of clinical and pathological parameters in recurrence of ICCA. RESULTS: ICCA patients showed significantly higher recurrence rate with lower 1-year and 3-year RFS rates than HCC patients (recurrence rate, 12.8% vs. 54.8%; 1-year and 3-year RFS rates, 94% and 84% vs. 67% and 42%). Of the 13 ICCA patients, 4 were diagnosed with a well-differentiated ICCA and 9 with a moderately-differentiated ICCA. There was no recurrence among those with a well-differentiated ICCA, whereas 78% recurred in the moderately-differentiated group. The median RFS time for the moderately-differentiated group was 13.0 months, yielding RFS rates of 56% at 1 year and 22% at 3 years. CONCLUSIONS: Liver transplantation in patients with a well-differentiated ICCA yielded excellent outcomes as compared to patients with a moderately-differentiated ICCA. This may allow consideration of transplantation in the setting of a well-differentiated ICCA, and obviate the need for adjuvant systemic treatment. Conversely, a moderately-differentiated ICCA carries a poor prognosis with a prohibitively high recurrence rate and poor survival. Liver transplantation should remain a contraindication in this group.

Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis.

Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. We designed a proof-of-principle study to examine if one series of Alemtuzumab infusions in sIBM patients depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease. Thirteen sIBM patients with established 12-month natural history data received 0.3 mg/kg/day Alemtuzumab for 4 days. The study was powered to capture > or =10% increase strength 6 months after treatment. The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements. Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies. Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies. During a 12-month observation period, the patients' total strength had declined by a mean of 14.9% based on Quantitative Muscle Strength Testing. Six months after therapy, the overall decline was only 1.9% (P < 0.002), corresponding to a 13% differential gain. Among those patients, four improved by a mean of 10% and six reported improved performance of daily activities. The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8% during the observation period but an improvement by 11.4% (P < 0.001) after 6 months, reaching the level of strength recorded 12 months earlier. Depletion of peripheral blood lymphocytes, including the naive and memory CD8+ cells, was noted 2 weeks after treatment and persisted up to 6 months. The effector CD45RA(+)CD62L(-) cells, however, started to increase 2 months after therapy and peaked by the 4th month. Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50% (P < 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and alphaB-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased. This proof-of-principle study provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one series of Alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. These encouraging results, the first in sIBM, warrant a future study with repeated infusions

Laparoscopic drainage of postappendectomy- retained fecalith and intra-abdominal abscess in the pediatric population.

Retained fecalith after an appendectomy is an uncommon complication frequently associated with intra-abdominal abscess. Treatment options include percutaneous, open, or laparoscopic drainage of the abscess and retrieval of the fecalith, as antibiotics and drainage alone are usually insufficient. Laparoscopy offers the advantages of enhanced visualization of the abdomen, improved cosmesis, and a quicker return to normal daily activities. The principles of laparoscopic treatment include the careful identification of all anatomic landmarks, as the abscesses are frequently adherent to intra-abdominal structures compromising the safety of the operation. In this paper, we present 2 cases of laparoscopic drainage of an intra-abdominal abscess with retrieval of a fecalith in pediatric patients 1 and 6 weeks after an initial appendectomy and a review the literature.

Challenges in therapeutic strategies for transplantation: where now from here?

The current standard of care in transplantation reliably achieves acceptable graft and patient survival but still depends on life long immunosuppression in most patients. Current strategies employ medications that, in general, inhibit distal events mediating rejection, namely T cell activation and cytotoxicity. They do not typically interfere with initial allorecognition or the factors that influence the direction of an immune response (towards cytotoxicity as opposed to anergy or regulation). Given the exponential amplification of immune responses, these proximal targets may be more efficient in preventing rejection. Recent laboratory investigations have identified several approaches, e.g., costimulation blockade, depletion, and hematopoietic chimerism, that influence the initial stages of the alloimmune response, or establish self-perpetuating means of eliminating rejection without chronic immunosuppression. This manuscript reviews methods of immune manipulation that the authors view as promising for future exploitation and transfer to the clinic. These therapies are similar in that they are viewed as attempts to influence the ability of the body to mount an immune response and its subsequent direction, as opposed to supplying late effector phase inhibition. While it is recognized as unlikely that any one therapy will universally lead to tolerance, the authors propose that these concepts will make immunosuppressive drug minimization more readily successful.