Ureteral stricture after pediatric kidney transplantation: Is there a role for percutaneous antegrade ureteroplasty?

INTRODUCTION: Ureteral obstruction following pediatric kidney transplantation occurs in 5-8% of cases. We describe our experience with percutaneous antegrade ureteroplasty for the treatment of ureteral stricture in pediatric kidney transplant patients. METHODS: We retrospectively reviewed all pediatric kidney transplantation patients who presented with ureteral stricture and underwent percutaneous antegrade ureteroplasty at our institution from July 2009 to July 2021. Variables included patient demographics, timing of presentation, location and extent of stricture, ureteroplasty technique and clinical outcomes. Our primary outcome was persistent obstruction of the kidney transplant. RESULTS: Twelve patients met inclusion criteria (4.2% of all transplants). Median age at time of ureteroplasty was 11.5 years (range: 3-17.5 years). Median time from kidney transplantation to ureteroplasty was 3 months. Patency was maintained in 50% of patients. Seven patients (58.3%) required additional surgery. Four patients developed vesicoureteral reflux. Patients with persistent obstruction had a longer time from transplant to ureteroplasty compared to those who achieved patency (19.3 vs 1.3 months, p = 0.0163). Of those treated within 6 months after transplantation, two patients (25%) required surgery for persistent obstruction (p = 0.06). All patients treated >1 year after transplantation had persistent obstruction following ureteroplasty (p = 0.06). CONCLUSION: Percutaneous antegrade ureteroplasty can be considered a viable minimally invasive treatment option for pediatric patients who develop early ureteral obstruction (<6 months) following kidney transplantation. In patients who are successfully treated with ureteroplasty, 67% can develop vesicoureteral reflux into the transplant kidney. Patients who fail early percutaneous ureteroplasty or develop obstruction >1 year after transplantation are best managed with surgical intervention.

Splenic Artery Transposition for Liver Transplantation: An Underutilized Technique?

BACKGROUND: Successful liver transplantation is dependent on restoration of hepatic arterial (HA) flow. Although uncommon, some native recipient HAs are not suitable or inadequate for anastomosis, thereby necessitating extra-anatomic HA reconstruction. Splenic artery transposition (SAT) is 1 method of HA reconstruction, in which the recipient splenic artery is transposed to reestablish perfusion of the donor liver. Due to the rarity of the technique, literature describing outcomes is limited. In the current report, we describe 3 patients (2 adults, 1 pediatric) who underwent complex upper abdominal surgery before whole-organ deceased donor liver transplantation with SAT. METHODS: The demographic and patient care information was collected prospectively and subsequently reviewed retrospectively. Given the de-identified nature of the data included, this study was exempt from approval from an ethics board. RESULTS: Recipient splenic arteries were dissected from their origin at the celiac trunk, for approximately 3-5 cm to ensure a gentle anterior-cranial curve toward the right upper quadrant, allowing anastomosis to the donor celiac trunk in an end-to-end fashion. Postoperatively, all 3 patients had rapid normalization of liver function tests and brisk HA flow demonstrated by Doppler ultrasound. Longer-term follow-up, ranging from 1 to 3 years, reveals continued patency of the reconstructed HAs and liver function tests within normal limits. CONCLUSIONS: Our experience points to SAT as a safe and effective technique for extra-anatomic HA reconstruction.

Liver transplant in a recently COVID-19 positive child with hepatoblastoma.

We describe the successful pediatric liver transplant for unresectable hepatoblastoma in a 4-year-old male with COVID-19 prior to transplant. The first negative NP swab was documented 1 month after initial diagnosis, when SARS-CoV-2 antibodies were also detected. The patient was actively listed for liver transplant after completing four blocks of a SIOPEL-4 based regimen due to his PRETEXT IV disease which remained unresectable. Following three additional negative NP swabs and resolution of symptoms for 4 weeks, he underwent a whole-organ pediatric liver transplant. COVID-19 positivity determined via NP swab SARS-CoV-2 real-time RT-PCR (Hologic Aptima SARS-CoV-2 RT-PCR assay). IgG and IgM total SARS- CoV-2 antibodies detected by Ortho Clinical Diagnostics VITROS® Immunodiagnostics Products Anti-SARS-CoV-2 Test. Patient received standard prednisone and tacrolimus-based immunosuppression without induction therapy following transplant. Post-transplant course was remarkable for neutropenia and thrombocytopenia, with discharge home on post-transplant day #11. Surveillance tests have remained negative with persistent SARS-CoV-2 IgG antibodies at 6 weeks after transplant. We describe one of the earliest, if not the first case of liver transplant following recent recovery from COVID-19 in a pediatric patient with a lethal malignant liver tumor. A better understanding of how to balance the risk profile of transplant in the setting of COVID-19 with disease progression if transplant is not performed is needed. We followed existing ASTS guidelines to document clearance of the viral infection and resolution of symptoms before transplant. This case highlights that pediatric liver transplantation can be safely performed upon clearance of COVID-19.

Intraoperative blood loss and transfusion during primary pediatric liver transplantation: A single-center experience.

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15-58) days compared to 11 (7-21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14-59) days compared to 11 (7-21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30-day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30-day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor.

No Gains in Long-term Survival After Liver Transplantation Over the Past Three Decades.

OBJECTIVE: The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year. SUMMARY OF BACKGROUND DATA: Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success. METHODS: We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression. RESULTS: There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P < 0.001). CONCLUSION: In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.

Reoperative complications following pediatric liver transplantation.

BACKGROUND: The aim of this study is to describe the incidence and impact of reoperation following pediatric liver transplantation, as well as the indications and risk factors for these complications. METHODS: All primary pediatric liver transplants performed at our institution between January 2012 and September 2016 were reviewed. A reoperative complication was defined as a complication requiring return to the operating room within 30 days or the same hospital admission as the transplant operation, excluding retransplantation. RESULTS: Among the 144 pediatric liver transplants performed during the study period, 9% of the recipients required reoperation. The most common indications for reoperation were bleeding and bowel complications. There was no significant difference in the graft survival of patients with a reoperation and those without a reoperation (p = 0.780), but patients with a reoperation had a significantly longer hospital length of stay (median of 39 days vs. 11 days, p = 0.001). Variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate were significantly associated with reoperation upon univariable logistic regression, but none of these risk factors remained statistically significant upon multivariable regression. CONCLUSION: At our institution, reoperation did not significantly impact graft survival. We identified variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate as risk factors for reoperation, although none of these risk factors demonstrated independent association with reoperation in a multivariable model. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level III.

Liver transplantation as definitive treatment of an unresectable mesenchymal hamartoma in a child with Beckwith-Wiedemann Syndrome.

Mesenchymal liver hamartomas are benign tumors that can cause life-threatening abdominal distension and carry a risk for malignant transformation. In this case report, we describe a 13-month-old male with Beckwith-Wiedemann Syndrome (BWS) who presented with multiple mesenchymal liver hamartomas causing severe intra-abdominal mass effect. Imaging revealed six large multi-locular cystic lesions, ranging from 3.8 to 8.9 cm in diameter. The large size and spread of the tumors necessitated liver transplantation for complete removal. The patient successfully underwent cadaveric piggyback liver transplantation at 25 months of age. He was alive at 16-month follow-up without evidence of tumor recurrence or graft rejection. Histological examination of the hepatic masses revealed mucinous epithelial lining and abundant hepatocytes in varying stages of differentiation, supporting the diagnosis of mesenchymal hamartoma. To the best of our knowledge, this is the first reported case of liver transplantation in a patient with BWS as definitive treatment for unresectable mesenchymal liver hamartoma.

An impressive choledochal cyst and its surgical resection.

INTRODUCTION: Choledochal cysts are rare congenital dilations of the biliary tree that can present with non-specific symptoms such as abdominal pain, jaundice, cholelithiasis and pancreatitis. Although most commonly identified in children, they can be found in the adult population. However, because of the non-specific symptoms, this diagnosis may be difficult to make in the adult. A physician therefore must keep this diagnosis within their differential, as it may arise in an unexpected patient population who may present with a convoluted work up. CASE PRESENTATION: In this report, we present the case of a 50-year-old African American woman with recurrent cholelithiasis, cholangitis and eventually obstructive jaundice despite undergoing a laparoscopic cholecystectomy six years prior. Her only work up at that point was a right upper quadrant ultrasound revealing gallbladder sludge, which led to her cholecystectomy. It was the persistence of her symptoms-abdominal pain, cholangitis and obstructive jaundice-previously attributed to chronic cholecystitis and choledocholithiasis that warranted further work up. After multiple physician visits, she was referred to our academic center after an ERCP was performed and she was found to have a dilation of her common bile duct consistent with a choledochal cyst. Furthermore, the ERCP identified multiple bile duct stones within the cyst. This was not identified on her original ultrasound or prior ERCPs. The patient underwent a complete cyst excision with Roux-en-Y hepaticojejunostomy and did well post-operatively. DISCUSSION: This report illustrates how choledochal cysts can be an elusive diagnosis, but may present with repeated infections, recurrent biliary stones, and biliary obstruction despite a cholecystectomy. Had she an MRCP prior to her cholecystectomy, she would likely have avoided multiple surgeries, and years of persistent symptoms. Choledochal cysts are associated with an increased risk of biliary malignancy and therefore cyst excision is the standard of care. CONCLUSION: Although rare, physicians need to keep this diagnosis in mind, and be aware of the clinical and imaging findings consistent with a choledochal cyst in order to facilitate appropriate work up, referral and treatment.

Liver transplantation in cystic fibrosis: a report from Baylor College of Medicine and the Texas Children's Hospital.

CF affects one of 2000 Caucasians, and approximately 25% are found to have CFLD for which OLT may be indicated. Timing of transplantation, contraindications, and survival are still widely debated. We report the outcomes of OLT for pediatric patients with CFLD from the largest children's hospital in the United States. Our records since September 1998 were analyzed for all patients undergoing OLT for CFLD. Nine patients were then compared to similar patients in the UNOS/OPTN database (n = 155). Survivals were calculated with the Kaplan-Meier method and compared using the log-rank test. All statistics were performed in SPSS 15.0. We performed OLT on nine pediatric patients with CFLD, with age ranging from nine to 17 yr at the time of transplant. Mean survival was 69.2 months; patient and allograft survivals at one and five yr were 88.9%, with one death at day 21 due to Aspergillus fumigatus sepsis. Two patients underwent concurrent multi-organ transplantation. One patient required double lung transplantation four yr after isolated OLT. Comparison to the UNOS/OPTN database revealed a trend toward improved survival. Patients with CF can achieve favorable outcomes after OLT, as we report excellent survivals for pediatric patients with CFLD.

Caroli disease patients have excellent survival after liver transplant.

BACKGROUND: Caroli disease (CD) is characterized by dilation of the intrahepatic biliary tree, which may result in malignancy. Treatments include management of symptoms and hepatic resection to decrease disease burden. In patients with CD not amenable to these treatments, orthotopic liver transplantation (OLT) has been used. This study examines if OLT is a reasonable treatment for patients with CD. MATERIALS AND METHODS: The United Network of Organ Sharing/Organ Procurement and Transplantation Network database between September 30, 1987 and March 31, 2011 was queried. Cases without patient or allograft survival time or without a diagnosis were excluded from analysis. Patients with CD were compared to patients with primary biliary cirrhosis (PBC), secondary biliary cirrhosis (BC), primary sclerosing cholangitis (PSC), and all indications for OLT. Survival analysis was performed by log-rank test and Kaplan-Meier. RESULTS: One hundred forty patients with CD were compared to 4797 patients with PBC, 489 patients with secondary BC, 6033 patients with PSC, and 92,210 patients post-OLT. Patient and allograft survivals of CD patients at 1, 3, 5, and 10 y are, respectively, 88.5%, 83.4%, 80.9%, and 77.8%; and 81.2%, 74.8%, 70.6%, and 67.9%. CD patients have significantly improved patient and allograft survivals after OLT compared to patients with secondary BC (P = 0.003, P = 0.015) and all other patients undergoing OLT (P = 0.003, P = 0.026). There is a trend towards long-term improved patient and allograft survival in transplanted patients with CD compared to patients with PBC and PSC. CONCLUSIONS: These results suggest that OLT should be considered an effective treatment modality for patients with CD resulting in excellent long-term outcomes.

Biliary adenofibroma with carcinoma in situ: a rare case report.

This case report exhibits a rare biliary tumor within the liver of a 53-year-old Caucasian woman. This exophytic, multicystic, 6.5 × 5.0 cm mass was composed of complex tubulocystic structures lined by nonmucin-secreting, biliary epithelium embedded in fibrous stroma, consistent with biliary adenofibroma. This is the seventh case described in the literature. Multiple foci of high-grade dysplasia/carcinoma in situ were found with a microscopic focus of invasive carcinoma in review of the pathology, making this only the second case reporting malignant transformation. It is presented to illustrate the premalignant potential in a biliary epithelial tumor currently categorized as benign.

Extended donors in liver transplantation.

Several criteria are used to differentiate between standard and extended allograft donors. These criteria include deceased after cardiac death, advanced donor age, steatosis, previous malignancy in the donor, hepatitis C virus-positive allografts, human T-cell lymphotropic virus-positive allografts, active infections in the donor, high-risk donors, split liver transplantations, and living donor liver transplantations. Review of the literature can lead each practitioner to incorporate extended criteria donors into their transplant program, thereby individualizing the use of these allografts, increasing the donor pool, and decreasing overall waitlist mortality.

Treatment of liver metastases in patients with neuroendocrine tumors: a comprehensive review.

Patients diagnosed with Neuroendocrine Tumors (NET) often are also diagnosed with Neuroendocrine Liver Metastases (NLM) during the course of their disease. NLM can cause significant morbidity and mortality, oftentimes much more than compared to patients with NET. Treatment options have been limited in the past, focusing on surgical resections, for which only a minority of patients are candidates. However, developments of new treatment modalities have progressed rapidly and patients with NLM now have significantly more options, including surgical-directed therapies; liver-directed therapies; and nonsurgical, non-liver-directed therapies. This review provides information about the roles of hepatic resection, orthotopic liver resection, radiofrequency ablation, hepatic artery embolization and hepatic artery chemoembolization, hepatic artery radioembolization and selective internal radiation therapy, peptide receptor radionuclide therapy, systemic chemotherapy, biotherapies including somatostatin analogs and interferon-α, vascular endothelial growth factor and mTOR targets, and microRNA-regulated pathways. Given these new options, the clinician can tailor therapy specific to the patient diagnosed with NLM, thereby giving the patient the best possible chance of prolonged survival.

Building a comprehensive genomic program for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, causing approximately 660,000 deaths worldwide annually. The preferred treatment of HCC is surgical resection or orthotopic liver transplantation (OLT) for patients meeting specific criteria. For patients outside these criteria, options are limited and include medical therapy, radiofrequency ablation, chemoembolization, or palliative measures, and these result in poor outcomes. Various centers at Baylor are elucidating the genomics of HCC to improve treatment options, with a focus on three etiologies: hepatitis C virus, hepatitis B virus, and non-viral. METHODS: Through collaborative efforts, we have established an effective specimen biobanking protocol, and we are using several techniques to analyze HCC, including whole genome sequencing, whole exome sequencing, gene-specific analysis, gene expression, and epigenetic analysis. RESULTS: We have completed whole genome sequencing on two patient samples, whole exome sequencing on 47 patient samples, gene-specific analysis on 94 patient samples, gene expression on 4 patient samples, and epigenetic analysis on 1 patient sample. CONCLUSIONS: We hope to use these results to define novel genetic therapeutic strategies that may work in conjunction with surgical approaches to improve long-term patient and graft survival rates in patients with HCC. We also aim to provide a functional framework of a comprehensive program for genomic analysis that may be imitated by other institutions and for other tumors in the global quest toward personalized genomic medicine.

A primer on a hepatocellular carcinoma bioresource bank using the cancer genome atlas guidelines: practical issues and pitfalls.

BACKGROUND: Since the advent of the human genome, the era of personalized genomic medicine is indisputably in progress. METHODS: In an effort to contribute to the evolving knowledge of genomic medicine, we have aimed directly at building a bioresource bank for hepatocellular carcinoma. This tumor bank is based on the rigorous guidelines set forth by the National Cancer Institute, and it offers analytes to help elucidate the mechanisms of progression from cirrhosis to malignancy, risk factors for recurrence, and applicability of current treatment options to a diverse group of people. CONCLUSIONS: Surgeons have a privileged position between patients (and their cancer) and the benches of basic science. Thus, we offer a primer based on our own experiences, from which surgeons may take elements to build their own bioresource bank for use in collaboration with others. We highlight some practicalities and pitfalls that could be overlooked, as well as a discussion of possible solutions.

Homozygous familial hypercholesterolemia: case series and review of the literature.

Introduction. Familial hypercholesterolemia (FH) is caused by nonfunctioning low-density lipoprotein (LDL) receptors, resulting in high serum cholesterol. Two types of FH are described: the heterozygous form is diagnosed in adults and responds well to medical therapy; the homozygous form is rare, diagnosed in children, and often requires multiple treatments to prevent complications. Cholesterol accumulation in tissues produces common clinical manifestations including cutaneous xanthomas, coronary artery disease, and aortic stenosis. Treatment options consist of lifestyle modifications, lipid-lowering medications, LDL aphaeresis, and orthotopic liver transplantation (OLT). Case Presentation. Two patients with FH presented at young ages due to characteristic cutaneous xanthomas. The patients underwent cardiac testing that revealed atherosclerotic changes. The patients received maximal medical therapy, but only experienced a small decrease in serum cholesterol and LDL levels. After several years of medical treatment without improvement of symptoms, the patients were listed for OLT. The transplantations were successful, and only one patient had a postoperative complication of acute rejection, treated successfully. Currently, both patients are doing well with regression of the cutaneous xanthomas and atherosclerotic changes. Conclusion. OLT is a safe and effective option for patients with homozygous FH refractory to maximal medical therapy and may represent the optimal treatment for these patients.

Neuroendocrine Liver Metastases and Orthotopic Liver Transplantation: The US Experience.

Liver transplantation remains a controversial therapy for Neuroendocrine liver metastases (NLM), with coflicting suvival data reported. The aim was to assess the evolution of outcomes for patients transplanted for NLM in the US, both before and after the introduction of the MELD scoring system in 2002. The UNOS/OPTN database was reviewed to identify patients diagnosed with NLM who subsequently underwent a liver transplantation from 1988 to March 2011 (n = 184); Patient survival was determined using Kaplan-Meier methods and log-rank tests, and cox regression analysis was performed, using SPSS 15.0 (SPSS, Inc, Chicago, IL). The overall NLM patient survivals in the pre-MELD era were 79.5%, 61.4%, and 49.2% at 1, 3, and 5 years, respectively. After the introduction of the MELD score, NET/NLM patients had improved overall patient survivals at 1, 3, and 5 years of 84.7%, 65%, and 57.8%. Patients transplanted after 2002 had an improved survival outcome. Notably, the overall patient survival for NET is not significantly different when compared to the outcomes of patients transplanted for HCC, in the current era. This progress acknowleges the significant improvement in outcomes for NLM patients after liver transplantation and the potential for further gain in the survival of otherwise nonsurgical, terminal patients.

Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: the UNOS experience.

Treatment for HEH does not follow a standardized algorithm. From clinical experience, it is assumed that pediatric patients with HEH will fare as well as other common pediatric liver tumors post-OLT. The UNOS dataset was examined for patients with pediatric OLT between 1987 and 2007. Patients were grouped into non-tumors, HB, HCC, HEH, and rare liver tumors. COD analysis was calculated using Fisher's exact test. Patient, allograft, and recurrence-free survival were compared using Kaplan-Meier curves and log-rank tests. A total of 366 patients with pediatric OLT were identified with primary liver tumors (HB - 237, HCC - 58, HEH - 35, other - 36). HEH patient survival (five yr: 60.6%) was poorer than non-tumor OLTpatient survival (five yr: 84.4%). Survival was worse when compared to HB (five yr: 72%) and rare liver tumors (five yr: 78.9%), but better than HCC (five yr: 53.5%). Allograft survival in HEH (five yr: 50.1%) lies between HB (five yr: 63.6%) and HCC (five yr: 42.8%). COD analysis demonstrates recurrence as a major cause in HB and HCC, but not for HEH or other liver tumors. The data suggest that patient survival may not be as high as previously believed and further investigation is warranted.