Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States.

BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

Cell-Free DNA as a Surveillance Tool for Hepatocellular Carcinoma Patients after Liver Transplant.

The liver is the world's sixth most common primary tumor site, responsible for approximately 5% of all cancers and over 8% of cancer-related deaths. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer, accounting for approximately 75% of all primary liver tumors. A major therapeutic tool for this disease is liver transplantation. Two of the most significant issues in treating HCC are tumor recurrence and graft rejection. Currently, the detection and monitoring of HCC recurrence and graft rejection mainly consist of imaging methods, tissue biopsies, and alpha-fetoprotein (AFP) follow-up. However, they have limited accuracy and precision. One of the many possible components of cfDNA is circulating tumor DNA (ctDNA), which is cfDNA derived from tumor cells. Another important component in transplantation is donor-derived cfDNA (dd-cfDNA), derived from donor tissue. All the components of cfDNA can be analyzed in blood samples as liquid biopsies. These can play a role in determining prognosis, tumor recurrence, and graft rejection, assisting in an overall manner in clinical decision-making in the treatment of HCC.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Mutations in latent membrane protein 1 of Epstein-Barr virus are associated with increased risk of posttransplant lymphoproliferative disorder in children.

Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at an increased risk of EBV-positive PTLD could influence clinical management of immunosuppression and other therapies, improving posttransplant outcomes. A 7-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at positions 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk of EBV-positive PTLD (clinical trials: NCT02182986). DNA was isolated from peripheral blood of EBV-positive PTLD case patients and matched controls (1:2 nested case:control), and the cytoplasmic tail of LMP1 was sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV-positive PTLD. DNA was sequenced from 32 PTLD case patients and 62 matched controls. Both LMP1 mutations were present in 31 of 32 PTLD cases (96.9%) and in 45 of 62 matched controls (72.6%) (P = .005; OR = 11.7; 95% confidence interval, 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk of development of EBV-positive PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV-positive PTLD.

Host microRNAs are decreased in pediatric solid-organ transplant recipients during EBV+ Post-transplant Lymphoproliferative Disorder.

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. In our previous studies EBV infection was demonstrated to markedly alter the expression of host B cell microRNA (miR). Specifically, miR-194 expression was uniquely suppressed in EBV+ B cell lines from PTLD patients and the 3'untranslated region of IL-10 was determined to be targeted by miR-194. Although EBV has been shown to regulate host miR expression in B cell lymphoma cell lines, the expression of miRs in the circulation of patients with EBV-associated PTLD has not been studied. The objective of this study was to determine if changes in miR expression are associated with EBV+ PTLD. In this study, we have shown that miR-194 is significantly decreased in EBV+PTLD tumors and that additional miRs, including miRs-17, 19 and 106a are also reduced in EBV+PTLD as compared to EBV-PTLD. We quantitated the levels of miRs-17, 19, 106a, 155, and 194 in the plasma and extracellular vesicles (EV; 50-70 nm as determined by nanoparticle tracking analysis) from pediatric recipients of solid organ transplants with EBV+ PTLD+ that were matched 1:2 with EBV+ PTLD- pediatric transplant recipients as part of the NIH-sponsored Clinical Trials in Organ Transplantation in Children, (CTOTC-06) study. Levels of miRs-17, 19, 106a, and 194 were reduced in the plasma and extracellular vesicles (EV) of EBV+ PTLD+ group compared to matched controls, with miRs-17 (p = 0.034; plasma), miRs-19 (p = 0.029; EV) and miR-106a (p = 0.007; plasma and EV) being significantly reduced. Similar levels of miR-155 were detected in the plasma and EV of all pediatric SOT recipients. Importantly, ~90% of the cell-free miR were contained within the EV supporting that EBV+ PTLD tumor miR are detected in the circulation and suggesting that EVs, containing miRs, may have the potential to target and regulate cells of the immune system. Further development of diagnostic, mechanistic and potential therapeutic uses of the miRs in PTLD is warranted.

Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma.

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.

Intestinal Autotransplantation and In-Situ Resection of Recurrent Pancreatic Head Intraductal Tubulopapillary Neoplasm with Portal Cavernoma: A Case Report.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) is a new entity of a rare premalignant pancreatic neoplasia, and a radical curative resection is indicated. As with other tumors of the root of the mesentery, the proximity of the lesion to large splanchnic vessels, abdominal aorta, and inferior vena cava poses major risks of a massive hemorrhage and visceral ischemia using conventional surgical techniques. At times, these lesions are amenable for resection using novel techniques developed from organ transplantation. Multivisceral (allo-) transplantation should be considered when radical resection of a benign tumor is likely to compromise portal flow and possibly precipitate acute liver failure, but it may be associated with a long waitlist time and tumor progression. Autotransplantation offers a safe and curative resection of otherwise inoperable tumors in a bloodless field, an excellent exposure, and prevention of warm ischemic injury to the affected viscera, which are then autotransplanted. METHODS: We describe the en bloc resection of a large and recurrent ITPN of the pancreas, distal stomach, proximal duodenum, transverse colon, superior mesenteric vein, and portal cavernoma, followed by intestinal autotransplantation. RESULTS: A complete tumor resection was achieved with negative margins, adequate cold preservation of the reimplanted intestine, and without significant hemorrhage. The patient was discharged from the hospital 10 days later. The histopathologic examination revealed free-margin resection of ITPN with an associated invasive carcinoma. The patient received adjuvant chemotherapy with folinic acid, fluorouracil, and oxaliplatin and remains disease-free 20 months after surgery. CONCLUSIONS: Autotransplantation offers curative resection of otherwise unresectable lesions of the root of the mesentery.

No Benefit of Prophylactic Surgical Drainage in Combined Liver and Kidney Transplantation: Our Experience and Review of the Literature.

Background: Contrasting results have emerged from limited studies investigating the role of prophylactic surgical drainage in preventing wound morbidity after liver and kidney transplantation. This retrospective study analyzes the use of surgical drain and the incidence of wound complications in combined liver and kidney transplantation (CLKTx). Methods: A total of 55 patients aged ≥18 years were divided into two groups: the drain group (D) (n = 35) and the drain-free group (DF) (n = 20). Discretion to place a drain was based exclusively on surgeon preference. All deceased donor kidneys were connected to the LifePort Renal Preservation Machine® prior to transplantation, in both simultaneous and delayed technique of implantation of the renal allograft. The primary outcome was the development of superficial/deep wound complications during the study follow-up. Secondary outcomes included the development of delayed graft function (DGF) of the transplanted kidney, primary non-function (PNF) and early allograft dysfunction (EAD) of the transplanted liver, graft failure, graft and patient survival, overall post-operative morbidity rate and length of hospital stay. Results: With a median follow-up of 14.4 months after transplant, no difference in the incidence of superficial/deep wound complications, except for hematomas, in collections size, intervention rate, PNF, EAD, graft failure and patient survival, was observed between the 2 groups. Significantly lower level of platelets, higher INR values, DGF, morbidity rates and length of hospital stay were reported post-operatively in the D group. Pre-operative hypoalbuminemia and longer CIT were included in the propensity score for receiving a drain and were associated with a significantly higher rate of developing a hematoma post-transplant. Conclusions: Absence of the surgical drain did not appear to adversely affect wound morbidity compared to the prophylactic use of drains in renal transplant patients during CLKTx.

En-Bloc Simultaneous Heart-Liver Transplantation in Adult Patients.

INTRODUCTION: Complexity of combined heart-liver transplantation has resulted in low adoption rates. We report a case series of adult patients receiving en-bloc heart-liver transplantation (HLTx), describe technical aspects, and discuss benefits of the technique. METHODS: Retrospective review of patients receiving en-bloc HLTx over 18 months, with clinical follow up to 1 year. Primary outcomes included postoperative mortality and major complications. Secondary outcomes included 1-year survival, cardiac or hepatic allograft rejection, and infection. RESULTS: Five patients received en-bloc HLTx. Mean recipient age was 43 years (26-63), and 3 patients were male. Total operative time was 430 minutes (393-480), cold and warm ischemic times of 85 (32-136) and 37.5 (31-47) minutes. Hospital survival was 80%. One patient died on postoperative day 55 due to fungal sepsis. Major postoperative complications included prolonged mechanical ventilation in 2 of 5 patients (40%), and renal insufficiency requiring hemodialysis in 2 of 5 patients (40%). Among patients discharged from hospital 1-year survival was 100%, with no evidence of rejection or infectious complications. CONCLUSION: En-bloc HLTx technique is a safe and effective strategy, decreasing operative times, and allograft ischemic times, whereas offering protection of implanted allografts during early stages of reperfusion while patient is hemodynamically supported on cardiopulmonary bypass.

Multivisceral transplant as an option to transplant cirrhotic patients with severe portal vein thrombosis.

Non-tumoral portal vein thrombosis (PVT) is a critical complication in the patient with advanced cirrhosis awaiting liver transplantation (LT). With the evolution of liver transplant (LT) technique, PVT has morphed from an absolute contraindication to a relative contraindication, depending on the grade of the thrombus. The Yerdel classification is one system of grading PVT severity. Patients with Yerdel class 1-3 PVT can undergo LT at centers with experience in complex portal vein (PV) dissection, thrombectomy, and reconstruction. Class 4 PVT, however, is even more complex and may require heroic techniques such as cavoportal hemitransposition, PV arterialization or multivisceral transplant (MVT). Some centers use a MVT back-up approach for patients with Yerdel class 4 PVT. In these patients, all organs with PV outflow are procured simultaneously as a cluster graft from a deceased donor (liver, pancreas, intestine±stomach). If physiologic PV inflow is established intraoperatively, the recipient undergoes LT. Otherwise the MVT graft is transplanted. MVT establishes physiologic PV flow, but transplantation of the intestine confers significant lifelong risks including rejection, graft-versus host disease and post-transplant lymphoma. Yerdel class 1-4 PVT patients undergoing successful LT have 5-year survival similar to non-PVT patients, while patients requiring full MVT experience somewhat higher mortality because of the complexity of the surgery and medical management.

Association of Alemtuzumab Induction With a Significantly Lower Incidence of GVHD Following Intestinal Transplantation: Results of 445 Consecutive Cases From a Single Center.

BACKGROUND: In intestinal transplantation, graft versus host disease (GVHD), while relatively rare, remains a major cause of morbidity and mortality posttransplant. Because of its rarity of occurrence, no multivariable analysis of risk factors for GVHD development has previously been reported. METHODS: We used Cox stepwise regression to determine the significant multivariable predictors of the hazard rate of developing biopsy-proven GVHD during the first 60 months posttransplant among 445 consecutive intestinal transplant cases at our center since 1994. RESULTS: GVHD was observed in 8.8% (39/445); median time-to-GVHD development (range) was 1.5 months (0.5-17.3 mo) posttransplant. Sites of GVHD included skin (N = 21), skin/gastrointestinal tract (N = 6), gastrointestinal tract/rectum (N = 4), skin/liver (N = 4), skin/lung (N = 2), skin/rectum (N = 1), and skin/bone marrow (N = 1). Three factors were selected into the Cox model offering significant protection from GVHD development (listed in order of selection): isolated intestine or liver-intestine (LI) (versus modified multivisceral [MV] or MV) allograft (P = 0.00003), alemtuzumab (versus no induction, anti-CD25, rabbit antithymocyte globulin, or rabbit antithymocyte globulin/rituximab) induction (P = 0.004), and liver inclusion (LI or MV) (P = 0.009). These results remained unchanged even after accounting for the propensity to receive alemtuzumab induction. Observed GVHD incidence was 2.4% (3/125), 0.0% (0/38), 17.9% (7/39), and 11.9% (29/243) for isolated intestine, LI, modified MV, and MV allografts, and 2.7% (3/113) versus 10.8% (36/332) for those receiving versus not receiving alemtuzumab induction, respectively. CONCLUSIONS: These results may help advance the current state of knowledge about risk factors for GVHD development following intestinal transplantation.

Clostridium difficile infection mimics intestinal acute cellular rejection in pediatric multivisceral transplant-A case series.

Clostridium difficile infection (CDI) is the most common health care-associated infection in the United States. Thirty-nine percent of intestinal transplant recipients may develop CDI. Induction of rejection has been reported as a rare event. To our knowledge, this will be the second report of an association between CDI and rejection in the literature. We describe our experience with four pediatric MVT recipients, three of whom on treatment of their CDI alone had resolution of biopsy findings of intestinal ACR. Our patients were males aged 2-5 years old who had their first CDI post-MVT occurring from 2 months to 15 months post-transplant. All first episodes of CDI were treated with a 10-14 day course of metronidazole with one additionally receiving vancomycin. All four recipients had recurrent CDI, and two recipients had septic shock as a manifestation of their CDI. Three recipients had biopsies showing mild rejection during episodes of CDI, and treatment of the CDI resulted in resolution of biopsy findings of rejection. Our case series suggests CDI may mimic ACR on intestinal biopsy. Treatment of rejection during active CDI carries the risk of over-suppression and worsening of CDI. Our experience has taught us that surveillance endoscopy for rejection may be deceiving during an active CDI, and if mild acute rejection is noted during active CDI, treatment of rejection can be safely delayed and potentially avoided.

Bloodstream infection caused by enteric organisms during the first 6 months after intestinal transplant.

BACKGROUND: Data on bloodstream infection (BSI) due to enteric organisms are scarce. METHODS: This retrospective study (1/2009-5/2017) was aimed to evaluate the incidence of BSI episodes due to enteric organisms during the first 6 months after intestinal transplant (ITx). Differences between the first (2009-2012) and second period (2013-2017) were evaluated as they differed from each other in the perioperative fungal prophylaxis and immunosuppressive regimen. RESULTS: Fifty-five adult patients were analyzed. Twenty-eight (51%) patients developed a total of 51 episodes of BSI. Mean time from transplant to BSI was 85.5 ± 58.8 days. The most common organisms were Klebsiella pneumoniae (33%), Enterococcus spp (31%), and Candida spp (18%). Twenty-three (45%) were multidrug resistant. The most common sources were gut translocation (35%), central line infection (20%), and intra-abdominal abscess (14%). Biopsy-proven rejection was associated with 16 (31%) of the BSI episodes. Patients during the first period were more likely to develop BSI (79% vs 41%, P = 0.03). There were more episodes of rejection associated with BSI in the first period (45% vs 14%, P = 0.03). The rate of reoperation into the abdominal cavity within 2 weeks after ITx was higher and the transplant hospital stay was longer among those who developed BSI (P = 0.04 for both). CONCLUSIONS: Half of our patients developed BSI (typically during the first 3 months). Gut translocation was the most common source of BSI. Patients with rejection and/or enteritis should be monitored closely for BSI.

Virologic response with 2 different cidofovir dosing regimens for preemptive treatment of adenovirus DNAemia in pediatric solid organ transplant recipients.

ADV is frequently seen in our pediatric SOT population. It presents in a variety of clinical presentation and can cause severe disease. In this population, there are very few studies to determine the safety of CDV as a potential therapeutic agent. We present the findings of our retrospective study evaluating the efficacy and safety of CDV as 2 separate dosing regimens. Regimen A uses the standard 5 mg/kg once a week (Regimen A), and the second uses the 1 mg/kg 3 times per week (Regimen B). Overall, the dosing regimen did not differ in nephrotoxicity, but Regimen B had a higher, although non-significant, rate of viral load clearance. This suggests that more frequent dosing at lower levels may be more efficacious without any significant side effects in our SOT population.

Pediatric patient with end-stage kidney disease secondary to Eagle-Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver-kidney transplant.

HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith-Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced-stage HBL, the presence of concomitant end-stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi-organ transplant. We report case of a 2-year-old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi-agent chemotherapy while on dialysis whom then underwent a simultaneous liver-kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi-organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.

CD52-Negative NK Cells Are Abundant in the Liver and Less Susceptible to Alemtuzumab Treatment.

BACKGROUND: T-cell depleting strategies have become an integral part of immunosuppressive regimens in organ transplantation. Alemtuzumab is a humanized monoclonal antibody against CD52, a cell-surface antigen on several immune cells. It has been suggested that lymphocyte depletion increases the risk of serious infections. However, this has not been observed with short-term alemtuzumab treatment in an organ transplant setting. For induction therapy using alemtuzumab following liver transplantation, we found that T- and B-cell numbers declined rapidly after alemtuzumab therapy; however, the natural killer (NK) cell number was sustained. NK cells are important effectors of innate immunity. Since the effects of alemtuzumab on NK cell functions, especially those of liver NK cells, are unknown, this study aimed to investigate this in detail. METHODS: To assess the effect of alemtuzumab on NK cells, samples were obtained from 7 organ donors and examined by flow cytometry using Annexin V and propidium iodide. Phenotypical and functional differences within subsets of NK cells with different levels of CD52 expression were determined by flow cytometry and in vitro cytotoxicity assays. RESULTS: CD52 expression on NK cells was lower than that on other lymphocyte subsets. The liver contained a large number of CD52- NK cells compared with the peripheral blood. In vitro treatment of liver-derived NK cells with alemtuzumab did not result in cell death. In contrast, co-incubation with alemtuzumab induced cell death in peripheral blood mononuclear cells and non-NK cells in the liver. Furthermore, CD52- liver NK cells were more cytotoxic and produced more IFN-γ than CD52+ NK cells after cytokine activation. CONCLUSION: The liver contains a large number of CD52- NK cells. These cells are refractory to alemtuzumab and have robust activity. These findings indicate that CD52- NK cells persist and could protect against infection after alemtuzumab-based lymphocyte depletion.

Pediatric liver transplantation: predictors of survival and resource utilization.

PURPOSE: We sought to identify factors associated with increased resource utilization and in-hospital mortality for pediatric liver transplantation (LT). METHODS: Kids' Inpatient Database (1997-2009) was used to identify cases of LT in patients <20 years old. RESULTS: Overall, 2905 cases were identified, with an in-hospital survival of 91 %. LT was performed most frequently in < 5 year olds (61 %), females (51 %), and Caucasians (56 %). LT was performed at urban teaching hospitals (97 %) and facilities with children's units (51 %). Indications included pathologic conditions of the biliary tract (44 %) and inborn errors of metabolism (34 %), though unspecified end stage liver disease was the most common (75 %). Logistic regression found higher mortality in children undergoing LT for malignant conditions (odds ratio: 4.8) and acute hepatic failure (OR 3.4). Cases complicated by renal failure (OR 7.7) and complications of LT (OR 2.7) had higher mortality rates. Resource utilization increased for children with renal failure and those with hemorrhage as a complication of LT, p < 0.05. CONCLUSION: Hospital survival is predicted by indication and complications associated with LT. Resource utilization increased with renal failure and complications related to LT. Admission length was sensitive to payer status, hospital characteristics, and UNOS region, whereas total costs were unaffected by payer status or hospital type.

Abdominal transplantation for unresectable tumors in children: the zooming out principle.

PURPOSE: To present our experience in abdominal transplantations to manage unresectable abdominal neoplasms in children and to describe the role of extensive surgeries in such cases. METHODS: This is a retrospective study of 22 abdominal transplantations in 21 patients for abdominal tumors over 16 years. Transplantation techniques included liver transplant (LT), multivisceral transplant (MVTx), and intestinal autotransplant (IA). Follow-up intervals ranged from 0.3 to 168 months (median 20 months). RESULTS: LT alone was performed in 15 patients for primary malignant (11) and benign (4) liver tumors. Pathological classification included HB hepatoblastoma (6), HCC hepatocellular cancer (3), hepatic epithelioid hemangioendothelioma HEH (1), angiosarcoma (1), benign vascular tumors (3), and adenoma (1). IA was performed in four patients for lesions involving the root of the mesentery; tumors of the head of pancreas (3) and mesenteric hemangioma (1). MVTx was performed in 2 patients for malignancies; pancreaticoblastoma (1), recurrent hepatoblastoma (1), and in one patient as a rescue procedure after IA failure. Four of the eleven patients who underwent LT for malignant liver tumor had metastatic disease at presentation. Six of them died of recurrent neoplasm (3), transplant-related complications (2), and underlying disease (1). All LT patients who had benign tumors are alive with functioning grafts. All IA patients survived and are on an oral diet, with one patient requiring TPN supplementation. One of the three patients who underwent MVTx died of metastatic disease. CONCLUSIONS: Allo/auto transplantation for abdominal tumors is a valuable modality when conventional treatments fail or are not feasible.

When and why portal vein thrombosis matters in liver transplantation: a critical audit of 174 cases.

OBJECTIVE: To identify complications associated with different techniques utilized to treat portal vein thrombosis (PVT) during primary liver transplantation and their impact on survival. BACKGROUND: PVT remains an intricate problem in liver transplantation, and the long-term outcomes of patients with PVT who undergo transplantation are not well defined. METHODS: We performed a retrospective cohort analysis of all consecutive adult patients who underwent primary isolated liver transplantation from 1998 to 2009 (median follow-up period, 89 months). The outcomes of patients with PVT were compared with those without PVT. RESULTS: Among 1379 recipients, 174 (12.6%) had PVT at the time of transplantation [83 (48%) complete and 91 (52%) partial]. Among PVT patients with reestablished physiological portal inflow (PVT: physiological group; n = 149), 123 underwent thrombectomies, 16 received interpositional vein grafts, and 10 received mesoportal jump grafts. In 25 patients, physiological portomesenteric venous circulation was not reconstituted (PVT: nonphysiological group; 18 underwent cavoportal hemitranspositions, 6 renoportal anastomoses, and 1 arterialization). The PVT: nonphysiological group suffered a significantly increased incidence of rethrombosis of the portomesenteric veins and gastrointestinal bleeding, with a marginal 10-year overall survival rate of 42% (no PVT, 61%; P = 0.002 and PVT: physiological, 55%; P = 0.043). The PVT: physiological and no PVT groups exhibited comparable survival rates (P = 0.13). No significant differences in survival were observed between complete and partial PVT as long as physiological portal flow was reestablished. CONCLUSIONS: The subset of PVT patients requiring nonphysiological portal vein reconstruction was associated with higher complication rates and suffered diminished long-term prognoses. For the most severe PVT cases, a comprehensive approach is critical to further improve outcomes.