Huge mesenchymal hamartoma in a young adult: a case report.

Mesenchymal hamartoma of the liver (MHL) is rare. Less than 50 adult cases have been described. Due to their potential degeneration or recurrence, a complete surgical resection must be performed. We describe a case of a 26-year-old with a palpable solid lesion, which displaced abdominal organs. Percutaneous needle biopsies suggested the diagnosis of MHL. A right hemi-hepatectomy without segment 1 was performed; the post-operative course was uneventful. The mesenchymal component of the tumour was reactive to desmin and smooth muscle actin. Low proliferation index was confirmed (MIB1). Genetic counselling: the sequencing analysis of DICER1 and CDKN1C gene was negative, DNA methylation analysis on the chromosome 11p15 region was normal. After 42 months, there was no recurrence. In conclusion, clinicians should consider MHL in the differential diagnosis. The dimension and the need of radicality impose major liver resections or liver transplantations, which should be performed in referral centres.

Living Donor Lung Transplantation After Hematopoietic Stem Cell Transplantation From the Same Donor: A Risk Worth Taking.

Living donor (LD) lung transplantation (LT) represents an exceptional procedure in Western countries. However, in selected situations, it could be a source of unique advantages, besides addressing organ shortage. We report a successful case of father-to-child single-lobe LT, because of the complications of hematopoietic stem cell transplantation from the same donor, with initial low-dose immunosuppressive therapy and subsequent early discontinuation. Full donor chimerism was hypothesized to be a mechanism of transplant tolerance, and this postulated immunological benefit was deemed to outweigh the risks of living donation and the possible drawbacks of single compared with bilateral LT. Favorable size matching and donor's anatomy, accurate surgical planning, and specific expertise in pediatric transplantation also contributed to the optimal recipient and donor outcomes. Ten months after LD LT, the patient's steadily good lung function after withdrawal of immunosuppressive therapy seems to confirm the original hypothesis.

Pancreatic ductal adenocarcinoma complete regression after preoperative chemotherapy: Surgical results in a small series.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) becomes a systemic disease from an early stage. Complete surgical resection remains the only validated and potentially curative treatment; disappointingly only 20% of patients present with a resectable tumour. Although a complete pathological regression (pCR) after the preoperative chemotherapy could intuitively lead to better outcomes and prolonged survival some reports highlighted significant rates of recurrence. CASES PRESENTATION: We describe three cases of pCR following preoperative chemotherapy for PDAC. The first two cases received neoadjuvant mFOLFIRINOX and PAX-G scheme for borderline resectable PDAC. Recurrence appeared 9 and 12 months after surgery. Although both patients started adjuvant therapy straight after the diagnosis of recurrence, the disease rapidly progressed and led them to death 12 and 15 months after surgery. The third case was characterized by germline BRCA2 mutation. The patient presented with PDAC of the body, intrapancreatic biliary stenosis and suspected peritoneal metastasis. One year later, after first and second-line chemotherapy, she underwent explorative laparoscopy and total spleno-pancreatectomy without evidence of viable tumour cells in the surgical specimen. At six months she is recurrence-free. CONCLUSIONS: Very few reports describe a complete pathological response following preoperative chemotherapy in pancreatic cancer. We observed three cases in the last three years with disappointing oncological results. Further investigations are needed to predict PDAC prognosis in pCR after chemotherapy.

Vaccination Recommendations in Solid Organ Transplant Adult Candidates and Recipients.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

Current Endovascular Management of Arterial Complications After Pediatric Liver Transplantation in a Tertiary Center.

PURPOSE: Pediatric liver transplant surgery is burdened by arterial complications whose endovascular treatment is not standardized. We report the outcomes of a cohort of pediatric recipients with hepatic artery complications treated by endoluminal procedures. MATERIALS AND METHODS: From December 2019 to December 2022, consecutive transplanted pediatric patients who underwent endovascular treatment of hepatic artery complications were reviewed. The analysis included: type of complication (occlusion, stenosis, pseudoaneurysm); onset (acute = < 15 days, subacute = 15-90 days, late = > 90 days); endovascular technique (angioplasty, stenting); complications and outcomes. Technical success was defined as the opacification of the hepatic artery at the final angiogram with < 50% residual stenosis and no pseudoaneurysms. Clinical success was defined by graft's and patient's survival. RESULTS: Seventeen patients (8 males; median age 33 months, IQR 9-103) underwent 21 hepatic arteriography procedures for predominantly acute or subacute occlusions (n = 7) or stenosis (n = 11) with concurrent pseudoaneurysms (n = 4). Primary and secondary technical success was achieved in 13/18 and 3/3 procedures, respectively, with overall technical success of 76%. Angioplasty alone was successful in 5/21 procedures; stent-retriever thrombectomy was performed in one occlusion with thrombosis; stenting was required in 9/17 (53%) patients. Clinical success was obtained in 14/17 (82%) patients with hepatic artery patency after a median of 367 days (IQR 114.5-500). Clinical failure occurred in 3 permanent occlusions, with 2 deaths and 1 re-transplantation. Procedure-related complications included minor events in 3/17 (18%) patients and 1/17 (6%) death. CONCLUSION: In liver transplanted children with hepatic artery complications, endovascular treatment may provide clinical success, with stenting often required in acute and subacute conditions. LEVEL OF EVIDENCE: Level 4.

Extended criteria liver donation after circulatory death with prolonged warm ischemia: a pilot experience of normothermic regional perfusion and no subsequent ex-situ machine perfusion.

BACKGROUND: Livers from controlled donation after circulatory death (cDCD) with very prolonged warm ischemic time (WIT) are regularly transplanted after abdominal normothermic regional perfusion (aNRP) plus ex-situ machine perfusion (MP). Considering aNRP as in-situ MP, we investigated whether the results of a pilot experience of extended criteria cDCD liver transplantation (LT) with prolonged WIT, with aNRP alone, were comparable to the best possible outcomes in low-risk cDCD LT. METHODS: Prospectively collected data on 24 cDCD LT, with aNRP alone, were analyzed. RESULTS: The median total and asystolic WIT were 51 and 25 min. Measures within benchmark cut-offs were: median duration of surgery (5.9 h); median intraoperative transfusions (3 units of red blood cells); need for renal replacement therapy (2/24 patients); median intensive care stay (3 days); key complications; overall morbidity, graft loss, and retransplantation up to 12 months; 12-month mortality (2/21 patients). The median hospital stay (33 days, due to logistics) and mortality up to 6 months (2/24 patients, due to graft-unrelated causes) exceeded benchmark thresholds. CONCLUSIONS: This pilot experience suggests that livers from cDCD with very prolonged WIT that appear viable during adequate quality aNRP may be safely transplanted, with no need for ex-situ MP, with considerable resource savings.

Improving outcomes of in situ split liver transplantation in Italy over the last 25 years.

BACKGROUND & AIMS: Split liver transplant(ation) (SLT) is still considered a challenging procedure that is by no means widely accepted. We aimed to present data on 25-year trends in SLT in Italy, and to investigate if, and to what extent, outcomes have improved nationwide during this time. METHODS: The study included all consecutive SLTs performed from May 1993 to December 2019, divided into three consecutive periods: 1993-2005, 2006-2014, and 2015-2019, which match changes in national allocation policies. Primary outcomes were patient and graft survival, and the relative impact of each study period. RESULTS: SLT accounted for 8.9% of all liver transplants performed in Italy. A total of 1,715 in situ split liver grafts were included in the analysis: 868 left lateral segments (LLSs) and 847 extended right grafts (ERGs). A significant improvement in patient and graft survival (p <0.001) was observed with ERGs over the three periods. Predictors of graft survival were cold ischaemia time (CIT) <6 h (p = 0.009), UNOS status 2b (p <0.001), UNOS status 3 (p = 0.009), and transplant centre volumes: 25-50 cases vs. <25 cases (p = 0.003). Patient survival was significantly higher with LLS grafts in period 2 vs. period 1 (p = 0.008). No significant improvement in graft survival was seen over the three periods, where predictors of graft survival were CIT <6 h (p = 0.007), CIT <6 h vs. ≥10 h (p = 0.019), UNOS status 2b (p = 0.038), and UNOS status 3 (p = 0.009). Retransplantation was a risk factor in split liver graft recipients, with significantly worse graft and patient survival for both types of graft (p <0.001). CONCLUSIONS: Our analysis showed Italian SLT outcomes to have improved over the last 25 years. These results could help to dispel reservations regarding the use of this procedure. IMPACT AND IMPLICATIONS: Split liver transplant(ation) (SLT) is still considered a challenging procedure and is by no means widely accepted. This study included all consecutive in situ SLTs performed in Italy from May 1993 to December 2019. With more than 1,700 cases, it is one of the largest series, examining long-term national trends in in situ SLT since its introduction. The data presented indicate that the outcomes of SLT improved during this 25-year period. Improvements are probably due to better recipient selection, refinements in surgical technique, conservative graft-to-recipient matching, and the continuous, yet carefully managed, expansion of donor selection criteria under a strict mandatory split liver allocation policy. These results could help to dispel reservations regarding the use of this procedure.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.

INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).

Liver Transplantation in Patients with Portal Vein Thrombosis: Revisiting Outcomes According to Surgical Techniques.

Surgical strategies for graft portal vein flow restoration vary from termino-terminal portal vein anastomosis to more complex bypass reconstructions. Although the surgical strategy strongly influences the post-operative outcome, the Yerdel grading is still commonly used to determine the prognosis of patients with portal vein thrombosis (PVT) undergoing liver transplantation (LT). We retrospectively reviewed the cases of LT performed on recipients with complex PVT at two high-volume transplantation centres. We stratified the patients by the type of portal vein reconstruction, termino-terminal portal vein anastomosis (TTA) versus bypass reconstruction (bypass group), and assessed a multivariable survival analysis. The rate of mortality at 90 days was 21.4% for the bypass group compared to 9.8% in the TTA group (p = 0.05). In the multivariable correlation analysis, only a trend for greater risk of early mortality was confirmed in the bypass groups (HR 2.5; p = 0.059). Yerdel grade was uninfluential in the rate of early complications. A wide range of surgical options are available for different situations of PVT which yield an outcome unrelated to the Yerdel grading. An algorithm for PVT management should be based on the technical approach and should include a surgically oriented definition of PVT extension.

Venous outflow obstruction in pediatric left lateral segment split liver transplantation.

BACKGROUND: Venous outflow obstruction (VOO) is a known cause of graft and patient loss after pediatric liver transplantation (LT). We analyzed the incidence, risk factors, diagnosis, management, and outcome of VOO in a large, consecutive series of left lateral segment (LLS) split LT with end-to-side triangular venous anastomosis. METHODS: We evaluated data collected in our prospective databases relative to all consecutive pediatric liver transplants performed from January 2006 to December 2021. We included in this study children undergoing LLS split liver transplant with end-to-side triangular anastomosis. Diagnosis of VOO was based on clinical suspicion and radiological confirmation. RESULTS: VOO occurred in 24/279 transplants (8.6%), and it was associated with lower graft weight (p = .04), re-transplantation (p = .008), and presence of two hepatic veins (p < .0001). In presence of two segmental veins' orifices, the type of reconstruction (single anastomosis after venoplasty or double anastomosis) was not significantly related to VOO (p = .87). Multivariable analysis indicated VOO as a risk factor for graft lost (hazard ratio 3.21, 95% confidence interval 1.22-8.46; p = .01). Percutaneous Transluminal Angioplasty (PTA) was effective in 17/22 (77%) transplants. Surgical anastomosis was redone in one case. Overall six grafts (25%) were lost. CONCLUSION: VOO after LLS split LT with end-to-side triangular anastomosis is an unusual but critical complication leading to graft loss in a quarter of cases. The occurrence of VOO was associated with lower graft weight, re-transplantation, and presence of two hepatic veins. PTA was safe and effective to restore proper venous outflow in most cases.

Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial).

BACKGROUND: Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. PATIENTS AND METHODS: The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). RESULTS: Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). CONCLUSION: LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

Successful Lung Transplantation From a Donor With Previous Severe COVID-19 Pneumonia.

Lungs from donors with previous COVID-19 could become a precious resource if proved safe. So far, only 3 successful lung transplantations from donors with previous mild COVID-19 have been reported. We describe a successful bilateral sequential lung transplantation from a donor who, 10 months before, had developed severe COVID-19 acute respiratory distress syndrome. No donor-derived viral transmission occurred, and 12 months after transplantation, the recipient's lung function is normal. In the presence of normal results of bronchoalveolar lavage and adequate functional and morphologic parameters, even a history of severe COVID-19 acute respiratory distress syndrome might not be considered a contraindication to lung donation.

Technical and Clinical Outcomes of Laparoscopic-Laparotomic Hepatocellular Carcinoma Thermal Ablation with Microwave Technology: Case Series and Review of Literature.

PURPOSE: To evaluate technical and clinical outcomes of intraoperative (laparoscopic/laparotomic) microwave ablation on HCC. MATERIALS AND METHODS: This is a retrospective single-center study evaluating consecutive patients treated for very early/early-stage HCC with intraoperative microwave ablation from 1 July 2017 to 30 June 2023. In these patients, a percutaneous US-guided approach was excluded due to the nodule's suboptimal visibility or harmful location and liver resection for a deep position or adherences. Data about the clinical stage, surgical approach, liver pathology and nodules characteristics, technical success, complications, and follow-up were collected. Technical success was intended as the absence of locoregional persistence at follow-up CT/MRI controls. RESULTS: A total of 36 cirrhotic patients (M:F = 30:6, median age 67 years) were enrolled; 18/36 (50%) had a single nodule, 13/36 (36%) had two, 4/36 had three (11%), and 1/36 had four (3%). Among the patients, 24 (67%) were treated with laparoscopy, and 12/36 (33%) with a laparotomic approach. Sixty HCCs of 16.5 mm (6-50 mm) were treated for 7 min (2-30 min) with 100 W of power. A total of 55 nodules (92%) were treated successfully and showed no residual enhancement at the first postoperative follow-up; the other 5/60 (8%) underwent chemo/radioembolization. There was one complication (3%): a biliary fistula treated with percutaneous drainage and glue embolization. The average hospital stay was 3.5 days (1-51 days), and patients were followed up on average for 238 days (13-1792 days). During follow-up, 5/36 patients (14%) underwent liver transplantation, 1/36 (2%) died during hospitalization and 1 after discharge. CONCLUSIONS: Laparoscopic/laparotomic intraoperative HCC MW ablation is feasible in patients unsuitable for percutaneous approach or hepatic resection, with rare complications and with good technical and clinical outcomes.

Physiological reno-portal bypass in liver transplantation with non-tumorous portal vein thrombosis.

Reno-portal anastomosis (RPA) in presence of spleno-renal shunts (SRS) is a physiological option to restore blood flow in liver transplantation with portal vein thrombosis (PVT). Diffuse splanchnic venous system thrombosis (complex PVT) is its main indication but RPA proved to be useful in selected cases of less extensive thrombosis (non-complex PVT). Up until now only two monocentric and one multicentric case series has been published on this topic in addition to few anecdotal reports. After 2014, we introduced RPA in our institution to manage some cases of complex PVT in presence of SRS. Here, we present the evolution of indication to RPA. From 2014 to 2020, we performed ten RPA: nine patients presented non-complex and one complex PVT. Overall early and late complication rates were 66.6% and 50%, respectively. Two patients developed RPA stenosis, treated by interventional radiology. Self-resolving acute kidney injury (AKI) was observed in three cases. No re-transplantation was necessary. RPA was patent in all patients, with a mean follow-up of 41.9 months. The overall patient survival was 70% at 1 year and 60% at 3 and 5 years. Four patients died at 1, 2, 3 and 20 months from LT. Causes of deaths were, respectively, stroke, cerebral infection, sepsis (MOF) and sudden variceal bleeding in sinusoidal obstruction syndrome. The relative simplicity and effectiveness of RPA in presence of SRS allowed us to rely more and more often on this technique in liver transplantation with challenging non-complex PVT.

Association between Kasai portoenterostomy at low caseload centres and transplant complications in children with biliary atresia.

BACKGROUND: Kasai portoenterostomy (KPE) is the preferred treatment for biliary atresia (BA) patients. It has been shown that the center caseload of KPE impacts on native liver survival. We aimed to define the impact of KPE caseload on complications at the time of liver transplantation (LT). METHODS: Retrospective data collection of LT for BA performed in our tertiary center between 2010 and 2018. The patients were grouped according to the caseload of the center that performed KPE: Group A (≥5 KPE/year) and Group B (<5 KPE/year). We analyzed total transplant time (TTT), hepatectomy time, amount of plasma and red blood cell (RBC) transfusions, occurrence of bowel perforations at LT. RESULTS: Among 115 patients, Group A (n 44) and Group B (n 71) were comparable for age, sex, PELD score, TTT. The groups differed for: median hepatectomy time (57 min, IQR = 50-67; vs 65, IQR 55-89, p = 0.045); RBC transfusions (95 ml, IQR 0-250; vs 200 ml, IQR 70-500, p = 0.017); bowel perforations (0/44 vs 15/71, p = 0.001). One-year graft loss in Group A vs Group B was 1/44 vs 7/71 (p = 0.239), whereas deaths were 0/44 vs 5/71 respectively (p = 0.183); 5/15 patients who had a perforation eventually lost the graft. CONCLUSIONS: This study found an association between KPE performed in low caseload center and the incidence of complications at LT. These patients tend to have a worse outcome. The centralization of KPE to referral center represents an advantage at the time of LT. MINI ABSTRACT: We studied the impact of Kasai portoenterostomy (KPE) caseload on complications at the time of liver transplantation (LT), in 115 patients. We found an association between KPE performed in low caseload center and increased bowel perforations and blood transfusions. We suggest to centralize to experienced center all children requiring KPE.

Liver transplantation in patients with non-neoplastic portal vein thrombosis: 20 years of experience in a single center.

BACKGROUND: The Yerdel classification is widely used for describing the severity of portal vein thrombosis (PVT) in liver transplant (LT) candidates, but might not accurately predict transplant outcome. METHODS: We retrospectively analyzed data regarding 97 adult patients with PVT who underwent LT, investigating whether the complexity of portal reconstruction could better correlate with transplant outcome than the site and extent of the thrombosis. RESULTS: 79/97 (80%) patients underwent thrombectomy and anatomical anastomosis (TAA), 18/97 (20%) patients underwent non-anatomical physiological reconstructions (non-TAA). PVT Yerdel grade was 1-2 in 72/97 (74%) patients, and 3-4 in 25/97 (26%) patients. Univariate analysis revealed higher 30-day mortality, 90-day mortality, 1-year mortality, and a higher rate of severe early complications in the non-TAA group than in the TAA group (p = .018, .001, .014, .009, respectively). In the model adjusted for PVT Yerdel grade, non-TAA remained independently associated with higher 30-day, 90-day, and 1-year mortality (p = .021, .007, and .015, respectively). The portal vein re-thrombosis and overall patient and graft survival rates were similar. DISCUSSION: In our experience, the complexity of portal reconstruction better correlated with transplant outcome than the Yerdel classification, which did not even appear to be a reliable predictor of the surgical complexity and technique.

Pre-Transplant Alpha-Fetoprotein > 25.5 and Its Dynamic on Waitlist Are Predictors of HCC Recurrence after Liver Transplantation for Patients Meeting Milan Criteria.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. METHODS: We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. RESULTS: The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9-16). The median time on the waitlist was 92 (41-170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6-6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). CONCLUSIONS: In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.

The frequency of rare and monogenic diseases in pediatric organ transplant recipients in Italy.

BACKGROUND: Rare diseases are chronic and life-threatening disorders affecting < 1 person every 2,000. For most of them, clinical symptoms and signs can be observed at birth or childhood. Approximately 80% of all rare diseases have a genetic background and most of them are monogenic conditions. In addition, while the majority of these diseases is still incurable, early diagnosis and specific treatment can improve patients' quality of life. Transplantation is among the therapeutic options and represents the definitive treatment for end-stage organ failure, both in children and adults. The aim of this paper was to analyze, in a large cohort of Italian patients, the main rare genetic diseases that led to organ transplantation, specifically pointing the attention on the pediatric cohort. RESULTS: To the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002-2019 timeframe. Overall, 49,404 recipients were enrolled in the cohort, 5.1% of whom in the pediatric age. For 40,909 (82.8%) transplant recipients, a disease diagnosis was available, of which 38,615 in the adult cohort, while 8,495 patients (17.2%) were undiagnosed. There were 128 disease categories, and of these, 117 were listed in the main rare disease databases. In the pediatric cohort, 2,294 (5.6%) patients had a disease diagnosis: of the 2,126 (92.7%) patients affected by a rare disease, 1,402 (61.1%) presented with a monogenic condition. As expected, the frequencies of pathologies leading to organ failure were different between the pediatric and the adult cohort. Moreover, the pediatric group was characterized, compared to the adult one, by an overall better survival of the graft at ten years after transplant, with the only exception of lung transplants. When comparing survival considering rare vs non-rare diseases or rare and monogenic vs rare non-monogenic conditions, no differences were highlighted for kidney and lung transplants, while rare diseases had a better survival in liver as opposed to heart transplants. CONCLUSIONS: This work represents the first national survey analyzing the main genetic causes and frequencies of rare and/or monogenic diseases leading to organ failure and requiring transplantation both in adults and children.

Extended Adhesion-Sparing Liver Eversion during Kasai Portoenterostomy for Infants with Biliary Atresia.

BACKGROUND: Despite the fact that Kasai portoenterostomy (KPE) is the primary treatment for biliary atresia (BA), liver transplantation (LT) remains the ultimate surgery for two-thirds of these patients. Their true survival rate with the native liver reflects the original KPE and the burden of post-operative complications. We report an original modification of the adhesion-sparing liver eversion (ASLE) technique during KPE that facilitates the total native hepatectomy at time of transplantation. METHODS: All consecutive patients with BA who underwent KPE at our department and subsequent LT at Paediatric Liver Transplant Centre at Papa Giovanni XXIII Hospital between 2010-2018 were retrospectively enrolled. All patients underwent ASLE during KPE. Patients' demographic data, type of KPE, total transplant time (TTT), hepatectomy time (HT), intra-operative packed red blood cells and plasma transfusions, intra- and post-operative complications were noted. RESULTS: 44 patients were enrolled. Median TTT and HT were 337 and 57 min, respectively. The median volume of packed red blood cell transfusion was 95 mL. No patients presented bowel perforation during the procedure or in the short post-operative course. No mortality after LT was recorded. CONCLUSIONS: In addition to the well-known advantages of the standard liver eversion technique, ASLE reduces the formation of intra-abdominal adhesions, lowering significantly the risk of bowel perforation and bleeding when liver transplantation is performed for failure of KPE.

Endoluminal vacuum-assisted closure (E-Vac) therapy for postoperative esophageal fistula: successful case series and literature review.

BACKGROUND: Treatment of esophageal perforations and postoperative anastomotic leaks of the upper gastrointestinal tract remains a challenge. Endoluminal vacuum-assisted closure (E-Vac) therapy has positively contributed, in recent years, to the management of upper gastrointestinal tract perforations by using the same principle of vacuum-assisted closure therapy of external wounds. The aim is to provide continuous wound drainage and to promote tissue granulation, decreasing the needed time to heal with a high rate of leakage closure. CASES PRESENTATION: A series of two different cases with clinical and radiological diagnosis of esophageal fistulas, recorded from 2018 to 2019 period at our institution, is presented. The first one is a case of anastomotic leak after esophagectomy for cancer complicated by pleuro-mediastinal abscess, while the second one is a leak of an esophageal suture, few days after resection of a bronchogenic cyst perforated into the esophageal lumen. Both cases were successfully treated with E-Vac therapy. CONCLUSION: Our experience shows the usefulness of E-Vac therapy in the management of anastomotic and non-anastomotic esophageal fistulas. Further research is needed to better define its indications, to compare it to traditional treatments and to evaluate its long-term efficacy.