Early Graft Loss With Suspected Seventh-Day Syndrome Following Pediatric Liver Transplantation.

INTRODUCTION: Allograft dysfunction within the first week posttransplant is an uncommon but known complication following liver transplantation. Seventh-Day Syndrome (7DS) is a rare complication of allograft dysfunction following liver transplantation characterized by the rapid clinical deterioration of a formerly well-functioning allograft within the first week posttransplant. The etiology of 7DS is unknown, and treatment options remain limited. While cases of graft survival have been reported, the risk of mortality remains exceedingly high without urgent retransplantation. METHODS: Patient data was retrospectively analyzed and a literature review performed. RESULTS: We present a unique case of split liver transplantation into two pediatric recipients in which one recipient developed rapidly progressive graft failure approximately 1 week postoperatively requiring urgent retransplantation while the other recipient had an unremarkable postoperative course. Upon clinical manifestation of progressive graft failure, the patient was treated with thymoglobulin, rituximab, intravenous immunoglobulin, and plasmapheresis. Despite this, the patient's clinical status continued to decline and she underwent retransplantation 11 days following her initial liver transplant. CONCLUSION: Seventh-Day Syndrome is a rare complication following liver transplantation that is associated with a high risk of morbidity and mortality. Our case adds to the limited literature on 7DS in children and is the first to report a comparative posttransplant clinical course in two recipients who received split grafts from the same donor.

Supramarginal resection of skull base chordomas: proof of concept and preliminary outcomes.

OBJECTIVE: The mainstay of treatment for skull base chordoma (SBC) is maximal safe resection followed by radiotherapy. However, even after gross-total resection (GTR), the recurrence rate is high due to microscopic disease in the resection margins. Therefore, supramarginal resection (SMR) could be beneficial, as has been shown for sacral chordoma. The paradigm of postoperative radiation therapy for every patient has also begun to change, as molecular profiling has shown variability in the risk of recurrence. The aim of this study was to present the concept of SMR applied to SBC, along with an individualized decision for postoperative radiation therapy. METHODS: This is a retrospective analysis of all SBCs operated on by the senior author between 2018 and 2023. SMR was defined as negative histological margins of bone and/or dura mater, along with evidence of bone resection beyond the tumor margins in the craniocaudal and lateral planes on postoperative imaging. Tumors were classified into 3 molecular recurrence risk groups (group A, low risk; group B, intermediate risk; and group C, high risk). Postoperative radiation therapy was indicated in group C tumors, in group B chordomas without SMR, or in cases of patient preference. RESULTS: Twenty-two cases of SBC fulfilled the inclusion criteria. SMR was achieved in 12 (55%) cases, with a mean (range) amount of bone resection beyond the tumor margins of 10 (2-20) mm (+40%) in the craniocaudal axis and 6 (1-15) mm (+31%) in the lateral plane. GTR and near-total resection were each achieved in 5 (23%) cases. Three (19%) tumors were classified as group A, 12 (75%) as group B, and 1 (6%) as group C. Although nonsignificant due to the small sample size, the trends showed that patients in the SMR group had smaller tumor volumes (13.9 vs 19.6 cm3, p = 0.35), fewer previous treatments (33% vs 60% of patients, p = 0.39), and less use of postoperative radiotherapy (25% vs 60%, p = 0.19) compared to patients in the non-SMR group. There were no significant differences in postoperative CSF leak (0% vs 10%, p = 0.45), persistent cranial nerve palsy (8% vs 20%, p = 0.57), and tumor recurrence (8% vs 10%, p = 0.99; mean follow-up 15 months) rates between the SMR and non-SMR groups. CONCLUSIONS: In select cases, SMR of SBC appears to be feasible and safe. Larger cohorts and longer follow-up evaluations are necessary to explore the benefit of SMR and individualized postoperative radiation therapy on progression-free survival.

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis.

BACKGROUND AND AIMS: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. APPROACH AND RESULTS: We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. CONCLUSIONS: We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study.

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

The cholestatic infant: updates on diagnosis and genetics.

PURPOSE OF REVIEW: Cholestasis in infants can indicate a serious hepatobiliary disease and requires timely assessment, diagnosis and intervention to prevent progression to serious liver decompensation. This report aims to highlight recently published studies regarding diagnosis and treatment of cholestasis in infants. RECENT FINDINGS: The evaluation of neonatal cholestasis can be challenging, requiring the assessment of a broad differential diagnosis in timely fashion. The Italian Society of pediatric gastroenterology, hepatology, and nutrition position paper on the evaluation of neonatal cholestasis is reviewed and compared to other published guidelines. In biliary atresia, the most time-sensitive of these diagnoses, serum matrix metalloproteinase-7 was studied in Japanese infants with biliary atresia with excellent diagnostic performance characteristics. Genetic testing panels are an increasingly used tool to help identify causes of cholestasis. An American experience of genetic testing in large cohort of infants identified a definite or possible genetic diagnosis in 11% of cholestatic infants. In the treatment of prutitus in Alagille syndrome and progressive familial intrahepatic cholestasis the clinical studies of two newly Food and Drug Administration approved ileal bile acid transport inhibitors are discussed. New information on the prevalence of cytomegalovirus and idiopathic cholestasis as other etiologies of infant cholestasis is also reviewed. Lastly, new insight on potential maternal microbiome regulation on biliary disease in neonates on experimental biliary atresia models is discussed. SUMMARY: Cholestasis in infants requires timely diagnosis and intervention. There are exciting new diagnostic and treatment options now being studied which could help minimize the likelihood of advanced liver disease and development of serious complications.

The Impact of COVID-19 on Job Prospects and Educational Training for Pediatric Gastroenterology Fellows.

OBJECTIVES: The COVID-19 pandemic has significantly affected graduate medical education with redistribution of trainees, altered clinical care, and decreased research. For graduating trainees, there remains concern that financial stability of health systems will affect the availability of new positions and hiring practices. This survey aims to evaluate the pandemic's impact from pediatric gastroenterology fellows' perspectives. METHODS: An anonymous survey was distributed by e-mail from June 11 to July 1, 2020 to all North American pediatric gastroenterology and advanced training fellows. The survey was tailored for the fellows' year of training including questions on education, clinical experience, research, and job outlook. RESULTS: Of the 434 pediatric gastroenterology fellows, 145 completed the survey. Of all respondents, negative impact was reported in 52% on clinical training, 46% research projects, and 41% procedural confidence. A majority (93%) of third-year respondents had a job contract signed at the time of the survey; however, 18% of those contracts were subsequently altered with 5 respondents having job contracts rescinded due to hiring freezes. Fifty-four percent of first- and second-year fellow respondents reported concern regarding finding a job with the majority being second-year fellows (78%). CONCLUSIONS: The COVID-19 pandemic continues to affect the medical system and healthcare professionals. This survey identified significant impact on job acquisition for graduating pediatric gastroenterology fellows and other critical components of training, which are likely applicable to other pediatric trainees. The survey results raise questions about potential strategies to improve medical education and job search success for graduating trainees.

Transient elastography assessment of liver allograft fibrosis in pediatric transplant recipients.

TE measures liver stiffness to assess fibrosis. Its use in post-transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB-4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007-2018) were eligible. Ninety-four patients (45%M) aged 1-21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty-nine percent received whole-liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16-33] IU/L. Twenty-one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P = .005 by Wilcoxon rank-sum test). APRI and FIB-4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56-0.85) with an optimal cut-point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB-4. TV grafts demonstrate similar correlation with histology as whole-liver grafts.

Impact of COVID-19 on Pediatric Gastroenterology Fellow Training in North America.

BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a "stay-at-home" order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. CONCLUSIONS: This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.

Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities: Development of an Assessment Tool and Curricular Resources.

BACKGROUND: Entrustable professional activities (EPAs) are critical activities performed by medical professionals, which can be observed and assessed. Adding on to common EPAs for all pediatric subspecialty trainees, specialty-specific EPAs for pediatric gastroenterology, hepatology, and nutritional fellowship were developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) EPA Task Force. METHODS: Having developed specialty-specific EPAs, building EPA assessments is the next logical step, as EPAs are included under a larger umbrella of competency-based assessment. Thus, the NASPGHAN EPA Task Force and Training Committee collaborated on an assessment tool and associated curricular resources to aid in tracking trainees' progression to entrustment within individual EPAs and readiness for independent practice. RESULTS: This manuscript reports the development of an EPA assessment tool, including guiding principles and the theory behind the assessment tool, with a focus on simple, meaningful assessments that can provide crucial performance feedback to trainees. In addition, curricular resources were developed, based on the assessment tool, to support training. Ultimately, it is the hope of the NASPGHAN EPA Task Force and Training Committee that this tool can aid training programs in providing formative feedback for trainees, and can be used by training programs and clinical competency committees for summative evaluation.

Pediatric post-transplant hepatic kaposi sarcoma due to donor-derived human herpesvirus 8.

In areas of the world where human herpesvirus 8 (HHV-8) is endemic, Kaposi sarcoma (KS) is a common SOT-associated cancer. In the United States, where the virus is not prevalent, PTKS is rare, and there is little literature on pediatric PTKS. We present a North American female who underwent deceased donor, left lateral segment liver transplant for biliary atresia at age 11 months. The donor was a male with no known history of KS, originally from an HHV-8-endemic country. Three months after transplantation, the patient developed liver nodules and portal vein thrombosis. Analysis of needle biopsy established the diagnosis of KS and confirmed that the transformed cells were donor-derived. HHV-8 viremia was detected, and ganciclovir dosing (which had been started prophylactically) was increased. Immunosuppression was changed from tacrolimus to sirolimus. After further disease progression, 8 cycles of paclitaxel were administered. Under this treatment, her nodules regressed, HHV-8 viremia resolved, and she had marked clinic improvement. Notably, the adult recipient of the right liver lobe from the same donor also developed PTKS. This is one of few pediatric PTKS cases described in the literature. It contributes to the mechanistic understanding of PTKS development, illustrating the risk posed by donors from HHV-8-endemic countries, as well as the potential for strong PTKS correlation between multiple recipients of organs from a single shared donor.

Validation of Transient Elastography Cut Points to Assess Advanced Liver Fibrosis in Children and Young Adults: The Boston Children's Hospital Experience.

OBJECTIVE: To derive an optimal liver stiffness measurement cut point to discriminate METAVIR fibrosis stage F4 and to validate both METAVIR fibrosis stage F3-F4 and F4 cut points in a separate cohort. STUDY DESIGN: Patients at Boston Children's Hospital with liver stiffness measurement from 2006 to 2016 and liver biopsy ≤12 months before screening were eligible. Patients enrolled 2006-2011 were used to calibrate liver stiffness measurement cut points and those enrolled 2011-2016 for validation. Diagnostic performance was assessed by receiver operating curve analysis. RESULTS: In total, 267 subjects were enrolled (97 calibration, 170 validation). The cohorts were similar with 54% male, aged 0-29 years (median 13 years), and liver diseases including 21% autoimmune, 19% viral, 11% nonalcoholic fatty liver, 9% cholestatic, and 9% primary sclerosing cholangitis. Cut points to discriminate F3-F4 and F4 were >8.6 kPa and >11.5 kPa with 81% and 84% accuracy, respectively. Applied to the validation cohort, accuracy was 67% and 75%, respectively. In 44 fasted subjects, the accuracy was 73% and 80%, respectively. CONCLUSION: This study validates previously determined liver stiffness measurement cut points of 8.6 kPa and 11.5 kPa to predict METAVIR F3-F4 and F4 fibrosis in children and young adults in separate cohorts. With increasing data on the utility and validity of liver stiffness measurement in children, transient elastography may help identify patients with greater risk of advanced fibrosis and those who need liver biopsy assessment and/or surveillance for the complications of cirrhosis in a variety of liver disorders.

Development and Validation of a Deep Neural Network Model for Prediction of Postoperative In-hospital Mortality.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The authors tested the hypothesis that deep neural networks trained on intraoperative features can predict postoperative in-hospital mortality. METHODS: The data used to train and validate the algorithm consists of 59,985 patients with 87 features extracted at the end of surgery. Feed-forward networks with a logistic output were trained using stochastic gradient descent with momentum. The deep neural networks were trained on 80% of the data, with 20% reserved for testing. The authors assessed improvement of the deep neural network by adding American Society of Anesthesiologists (ASA) Physical Status Classification and robustness of the deep neural network to a reduced feature set. The networks were then compared to ASA Physical Status, logistic regression, and other published clinical scores including the Surgical Apgar, Preoperative Score to Predict Postoperative Mortality, Risk Quantification Index, and the Risk Stratification Index. RESULTS: In-hospital mortality in the training and test sets were 0.81% and 0.73%. The deep neural network with a reduced feature set and ASA Physical Status classification had the highest area under the receiver operating characteristics curve, 0.91 (95% CI, 0.88 to 0.93). The highest logistic regression area under the curve was found with a reduced feature set and ASA Physical Status (0.90, 95% CI, 0.87 to 0.93). The Risk Stratification Index had the highest area under the receiver operating characteristics curve, at 0.97 (95% CI, 0.94 to 0.99). CONCLUSIONS: Deep neural networks can predict in-hospital mortality based on automatically extractable intraoperative data, but are not (yet) superior to existing methods.

Hepatic Inflammation May Influence Liver Stiffness Measurements by Transient Elastography in Children and Young Adults.

OBJECTIVES: Transient elastography (TE) measures liver stiffness to assess fibrosis. Studies in adults have shown that inflammation increases stiffness, leading to an overestimation of fibrosis. We investigated the contribution of inflammation to liver stiffness measurements (LSMs) in children/young adults. METHODS: This was a cohort analysis of children/young adults who underwent TE within 1 year of liver biopsy. Alanine aminotransferase (ALT) was obtained within 30 days of the biopsy and LSM. Fibrosis was assessed by METAVIR stage and inflammation by ALT and Ishak score. Data were stratified into METAVIR F0-F2 versus F3-F4. Change between ALT and LSM over time was also assessed. RESULTS: A total of 154 patients (50% male patients) ages 3 weeks to 24 years (18% <3 years) were studied. Diagnoses included autoimmune (N = 38, 25%), viral (N = 25, 16%), cholestasis (N = 17, 11%), fatty liver (N = 9, 6%), biliary atresia (N = 8, 5%), metabolic (N = 5, 3%), allograft rejection (N = 4, 3%), and other (N = 48, 31%). Thirty-four percent of patients had F3-F4. In patients with F0-F2, the proportion of those with LSM >8.6 kPa increased with increasing ALT (P = 0.002). In patients with F3-F4, there was no association between ALT and LSM (P = 0.17). A correlation between change in ALT and LSM was observed in patients with no/minimal fibrosis and inflammatory liver diseases (r = 0.33). CONCLUSIONS: In children with no/minimal hepatic fibrosis and inflammatory liver disease, high ALT values are associated with LSM in the range typical of advanced fibrosis. However, with more advanced fibrosis, inflammation does not appear to contribute to LSM. Caution must be taken when interpreting LSM for assessing fibrosis severity in the setting of inflammation.

Outcomes after discontinuation of routine use of transanastomotic biliary stents in pediatric liver transplantation at a single site.

Routine use of transanastomotic biliary stents (RTBS) for biliary reconstruction in liver transplantation (LT) is controversial, with conflicting outcomes in adult randomized trials. Pediatric literature contains limited data. This study is a retrospective review of 99 patients who underwent first LT (2005-2014). In 2011, RTBS was discontinued at our center. This study describes biliary complications following LT with and without RTBS. 56 (56%) patients had RTBS. Median age at LT was 1.9 yr (IQR 0.7, 8.6); 55% were female. Most common indication for LT was biliary atresia (36%). Most common biliary reconstruction was Roux-en-Y choledochojejunostomy (75% with RTBS, 58% without RTBS, p = 0.09). Biliary complications (strictures, bile leaks, surgical revision) occurred in 23% without significant difference between groups (20% with RTBS, 28% without RTBS, p = 0.33). Patients with RTBS had routine cholangiography via the tube at 6-8 wk; thus, significantly more patients with RTBS had cholangiograms (91% vs. 19%, p < 0.0001). There was no difference in the number of patients who required therapeutic intervention via endoscopic or percutaneous transhepatic cholangiography (11% with RTBS, 19% no RTBS, p = 0.26). Routine use of RTBS for biliary reconstruction in pediatric LT may not be necessary, and possibly associated with need for costlier, invasive imaging without improvement in outcomes.

The Natural History of Primary Sclerosing Cholangitis in Children: A Large Single-Center Longitudinal Cohort Study.

OBJECTIVES: Data regarding pediatric primary sclerosing cholangitis (PSC) natural history are limited. We describe a large pediatric PSC cohort with longitudinal follow-up. METHODS: The present study records review of pediatric patients with PSC diagnosed between 1984 and 2014. RESULTS: N = 120 (63% M) ages 1 to 21 years (median 14 years) at diagnosis. 27% (31/113) had autoimmune sclerosing cholangitis (ASC), 24% had exclusive small duct PSC, METAVIR stage was F3-F4 in 41%. Eighty-one percent of patients with PSC had inflammatory bowel disease (IBD); most had ulcerative/indeterminate colitis (72/97), typically pancolitis (40/72). PSC-IBD was more common than ASC-IBD (85% vs 68%, P = 0.03). Median follow-up was 3.7 years (interquartile range [IQR] 1.5, 6.9). Median gamma glutamyl transferase decreased from baseline of 221 U/L (IQR 110, 425) to 104 U/L by 1 year postdiagnosis ([IQR 18,229], P < 0.0001), and then changed little. Mean fibrosis stage at diagnosis was 2.3 ±â€Š1.4 (N = 91), and at 1 to 5 years was 2.6 ±â€Š1.3 (N = 20). Transplant-free survival at 10 year was 89%; there were 6 liver transplants, 2 in patients with small duct PSC and 4 with diffuse large duct PSC. Although the cirrhosis rate was not significantly different in PSC with IBD versus without (22% vs 41%, P = 0.06), the former had a lower rate of liver transplantation (2% vs 18%, P = 0.01). The rate of cirrhosis was lower in patients diagnosed with IBD before PSC (15% vs 31%, P = 0.05). CONCLUSIONS: In this largest reported pediatric PSC cohort, liver transplantation rate at 10 years was lower than that reported in adults. ASC and PSC had similar biochemical abnormalities and degree of fibrosis at diagnosis. PSC that developed after IBD diagnosis had a milder course, possibly reflecting earlier disease detection or milder phenotype.

Endoscopic Endonasal Approach to the Ventral Petroclival Fissure: Anatomical Findings and Surgical Techniques.

Objective The endoscopic endonasal approach has emerged as an excellent option for the treatment of lesions involving the petroclival fissure (PCF). Here, we investigate the surgical anatomy of the ventral PCF and its application in endoscopic endonasal surgery. Methods Sixteen head specimens were used to investigate the anatomical features of PCF and relevant technical nuances in translacerum, extreme medial, and contralateral transmaxillary (CTM) approaches. Two representative endoscopic endonasal surgeries involving the PCF were selected to illustrate the clinical application. Results From the endoscopic endonasal view, the ventral PCF is presented as a lazy L sign, which is divided into two distinct segments: (1) upper (or petrosphenoidal) segment, which extends vertically from the foramen lacerum inferiorly to the junction of the petrosal process of sphenoid bone and petrous apex superiorly, and (2) lower (or petroclival) segment, which extends inferolaterally from the foramen lacerum to the ventral jugular foramen. Approaching both segments of the ventral PCF first requires full exposure of the foramen lacerum, followed either by exposure of the anterior wall of cavernous sinus and paraclival internal carotid artery for upper segment access, or transection of pterygosphenoidal fissure and Eustachian tube mobilization for lower segment access. Combined with a CTM approach, the lateral extension of the surgical access can be improved for both upper and lower segment PCF approaches. Conclusion This study provides a detailed investigation of the microsurgical anatomy of the ventral part of PCF, relevant surgical approaches, and technical nuances that may facilitate its safe exposure intraoperatively.

Symptomatic perianeursymal cyst development 20 years after endovascular treatment of a ruptured giant aneurysm: Case report and updated review.

Perianeurysmal cysts are a rare and poorly understood finding in patients both with treated and untreated aneurysms. While the prior literature suggests that a minority of perianeurysmal cysts develop 1-4 years following endovascular aneurysm treatment, this updated review demonstrates that nearly half of perianeurysmal cysts were diagnosed following aneurysm coiling, with the other half diagnosed concurrently with an associated aneurysm prior to treatment. 64% of perianeurysmal cysts were surgically decompressed, with a 39% rate of recurrence requiring re-operation. We report a case of a 71-year-old woman who presented with vertigo and nausea and was found to have a 3.4 cm perianeurysmal cyst 20 years after initial endovascular coiling of a ruptured giant ophthalmic aneurysm. The cyst was treated with endoscopic fenestration followed by open fenestration upon recurrence. The case represents the longest latency from initial aneurysm treatment to cyst diagnosis reported in the literature and indicates that the diagnosis of perianeurysmal cyst should remain on the differential even decades after treatment. Based on a case discussion and updated literature review, this report highlights proposed etiologies of development and management strategies for a challenging lesion.

Endoscopic Endonasal Resection of a Thyroid-Stimulating Hormone-Secreting Pituitary Adenoma With Invasion of the Medial Wall of the Cavernous Sinus.

Thyroid-stimulating hormone-secreting adenomas (TSH-oma) are exceptionally rare.1 The primary treatment is surgical resection with radiation and pharmacotherapy postoperatively if subtotal resection, especially with cavernous sinus invasion.2 We present the case of a 29-year-old man with TSH-oma with cavernous sinus medial wall invasion. This is the first documented case with selective resection of the cavernous sinus medial wall to achieve a complete resection and biochemical remission in TSH-oma through endoscopic endonasal approach. The patient had elevated TSH and thyroid hormones with symptoms of weight loss, palpitations, excess sweating, and decreased endurance. MRI revealed a 1.3 × 2.1 × 1.2 cm contrast-enhancing sellar mass with rightward pituitary gland displacement without evidence of cavernous sinus invasion (Knosp 2). The patient consented to procedure/publication. No institutional review board approval needed per institution. We performed standard resection of the firm sellar tumor portion and noted that there was tumor invasion into the left cavernous sinus medial wall dura. The bony opening was expanded to expose the anterior wall of the cavernous sinus, which was opened to identify the cavernous internal carotid artery and the medial wall attachments. The thickened medial wall was completely resected. We achieved a complete tumor resection, and the patient's TSH and thyroid hormone dropped to a desired threshold.3 Tumor stained for GATA3 and PIT1, characterizing the TSH-oma.4,5 Understanding cavernous sinus vascular and ligamentous anatomy allows for safe separation of invaded medial wall dura from the cavernous internal carotid artery,6 allowing for a more complete tumor resection, improving surgical cure rates, and sparing the patient from future radiation and pharmacotherapy.