Duodenal Gastrointestinal Stromal Tumor: A Rare Disease in a Young Adult Female Patient Presenting with Life-Threatening Hemorrhage.

Duodenal gastrointestinal stromal tumors (dGISTs) may be a source of life-threatening hemorrhage that leads to emergency surgical care, precluding tumor staging and the planning of an elective treatment. In this study, we report a case of potentially lethal bleeding dGIST in a young woman successfully treated by an organ-preserving elective surgery after endoscopic and angiographic hemostasis. A 26-year-old female patient was admitted to the Emergency Unit of our hospital with the complaints of hematemesis and melena in the previous 12 h. An upper endoscopy showed a 4-cm submucosal lesion, between the 2nd and 3rd part of the duodenum, in the lateral wall, with massive bleeding arising from central ulceration. Hemostasis was initially achieved endoscopically and then optimized by transarterial embolization. After a contrast-enhanced CT, the patient underwent planning elective surgery. Intraoperatively, a 3-cm lesion was confirmed and resected by excision of the full-thickness duodenum with adequate free margins. Immunohistochemical analysis of the specimen revealed to be a dGIST, with a low mitotic count (<5 mitosis/50 high power field), and tumor necrosis present in <50% of the lesion. The patient had an uneventful course.

Cost analysis of a long-term randomized controlled study in biliary duct-to-duct anastomotic stricture after liver transplantation.

Multiple plastic stent (MPS) for biliary anastomotic stricture (AS) after liver transplantation requires multiple procedures with consequent costs. To compare the success, adverse events and treatment-related costs of fully covered self-expandable metal stents (FCSEMS) versus MPS. Thirty liver transplant (LT) patients with clinically relevant naïve AS were prospectively randomized to FCSEMS or MPS, with stent numbers increased at 3-month intervals. Treatment costs per patient were calculated for endoscopic retrograde cholangiopancreatography (including all devices and stents) and overall hospital stay. Radiological success was achieved in 73% of FCSEMS (median indwelling period of 6 mos) and 93% of MPS patients (P = NS) (median period of 11 mos). AS recurrence occurred in 36% of FCSEMS and 7% of MPS patients (P = NS), and AS re-treatment was needed in 53% and 13% (P < 0.01), respectively, during follow-up of 60 (34-80) months. Stents migrated after 29% and 2.6% of FCSEMS and MPS procedures, respectively (P < 0.01). Including re-treatments, long-term clinical success was achieved in 28/30 (93%) patients. Overall treatment-related costs were similar between groups. In the subgroup of LT patients in clinical remission after first-line treatment, treatment costs were 41% lower per FCSEMS patient compared with MPS patients. FCSEMS did not perform better than MPS. FCSEMS migration increased the rate of re-treatment and costs.

Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.

Population Dynamics in Italian Canids between the Late Pleistocene and Bronze Age.

Dog domestication is still largely unresolved due to time-gaps in the sampling of regions. Ancient Italian canids are particularly understudied, currently represented by only a few specimens. In the present study, we sampled 27 canid remains from Northern Italy dated between the Late Pleistocene and Bronze Age to assess their genetic variability, and thus add context to dog domestication dynamics. They were targeted at four DNA fragments of the hypervariable region 1 of mitochondrial DNA. A total of 11 samples had good DNA preservation and were used for phylogenetic analyses. The dog samples were assigned to dog haplogroups A, C and D, and a Late Pleistocene wolf was set into wolf haplogroup 2. We present our data in the landscape of ancient and modern dog genetic variability, with a particular focus on the ancient Italian samples published thus far. Our results suggest there is high genetic variability within ancient Italian canids, where close relationships were evident between both a ~24,700 years old Italian canid, and Iberian and Bulgarian ancient dogs. These findings emphasize that disentangling dog domestication dynamics benefits from the analysis of specimens from Southern European regions.

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial.

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

Laparoscopic liver resections for hepatocellular carcinoma. Can we extend the surgical indication in cirrhotic patients?

BACKGROUND: Evidence on the value of laparoscopic liver resections (LLR) for hepatocellular carcinoma (HCC) and severe cirrhosis is still lacking. The aim of this study is to assess surgical and oncological outcomes of LLR in cirrhotic HCC patients. METHODS: The analysis included 403 LLR for HCC from seven European centres. 333 cirrhotic and 70 non-cirrhotic patients were compared. A matched comparison was performed between 100 Child-Pugh A and 25 Child-Pugh B patients. RESULTS: There was no difference in blood loss (250 vs. 250 mL, p 0.465) and morbidity (28.6 vs. 26.4%, p 0.473) between cirrhotics and non-cirrhotics, and liver-specific complications were similar (12.8 vs. 12%, p 0.924). The sub-analysis revealed similar perioperative outcomes in either Child-Pugh A or B patients. Noteworthy, ascitis (11 vs. 12%, p 0.562) and liver failure (3 vs. 4%, p 0.595) were not different. ASA score (OR 1.76, p 0.034) and conversion (OR 2.99, p 0.019) were risk factors for major morbidity. Despite lower recurrence-free survival in cirrhotics (43 vs. 55 months, p 0.034), overall survival was similar to non-cirrhotic patients (84 vs. 76.5, p 0.598). CONCLUSION: LLR for HCC appear equally safe in cirrhotic and non-cirrhotic patients, and the advantages can be witnessed in those with advanced cirrhosis. Severe comorbidities and conversion should be considered risk factors for complications-rather than the severity of cirrhosis and portal hypertension-when liver resection is performed laparoscopically. Such results may be of great interest to liver surgeons and hepatologists when deciding on the management of HCC within cirrhosis.

Bridging all oral DAA therapy from wait time to post-liver transplant to improve HCV eradication?

BACKGROUND & AIMS: Recurrence of hepatitis C is a major cause of graft loss and shortened survival in patients receiving a liver transplant (LT) for end-stage hepatitis C virus (HCV) infection. The only way to improve graft and patient outcomes is a successful eradication of HCV infection by antiviral therapy either before or after transplant. This was achievable in a small proportion of recipients by IFN-based regimens, but could be obtained in the majority of them by using DAA IFN-free regimens before/after transplant. METHODS: We describe a patient with decompensated cirrhosis because of severe recurrent hepatitis C, who had a retransplant following treatment with a combination of sofosbuvir and riba virin that started during the waiting time and was carried over during both the transplant and post-transplant phases for an overall period of 24 weeks. The patient gave a written consent to receive Sofosbuvir plus Rbv therapy pre and post-transplant. RESULTS: Post-transplant serum HCV-RNA remains undetectable 24 weeks after discontinuing sofosbuvir and ribavirin (SVR24). CONCLUSIONS: Waiting for direct antiviral agents combinations, our findings not only support the use of sofosbuvir plus ribavirin as the first-line treatment in all patients on the LT waiting list, but also suggest to bridge treatment to the post-transplant period in case HCV RNA undetectability for at least 30 days has not been achieved at the time of LT.

Liver transplantation for hepatocellular carcinoma in a patient with a novel telomerase mutation and steatosis.

We report the case and discuss the outcome of a 63-year-old man, who was transplanted for hepatocellular carcinoma arising from cirrhosis associated with non-alcoholic fatty liver and diabetes. Because of co-existent well-compensated idiopathic familial pulmonary fibrosis and family history of cryptogenic cirrhosis, he was screened and found positive for a novel c.2062 C>G telomerase (TERT) mutation, encoding for the protein Glu668Asp variant, which was also confirmed in the neoplastic tissue. TERT mutations have very recently been associated with a spectrum of familial hepatic liver diseases often characterized by steatosis and hepatic iron overload, and have been reported to represent a frequent risk factor for cirrhosis, being observed in as much as 3-8% of unselected patients with different liver diseases. Due to the systemic involvement of telomerase diseases very likely influencing the clinical outcome, and the peculiar biological features of hepatocellular carcinoma arising in this context, we suggest that patients with cryptogenic cirrhosis or other suggestive features should be screened for TERT mutations and specific treatment algorithms elaborated for this disease.

Transient elastography identifies liver recipients with nonviral graft disease after transplantation: a guide for liver biopsy.

Transient elastography (TE) reliably predicts the severity of recurrent hepatitis C virus after orthotopic liver transplantation (OLT); however, its accuracy in evaluating nonviral liver graft damage is unknown. Between 2006 and 2009, 69 OLT recipients [37 for hepatitis B virus/hepatitis D virus (recurrence-free), 20 for autoimmune/cholestatic liver disease, 6 for alcoholic liver disease, and 6 for mixed etiologies] underwent protocol/on-demand liver biopsy (LB) and concomitant TE. A histological diagnosis of graft disease was made according to criteria defined by the Banff working group. Sixty-five patients (94%) had reliable TE examinations during a median post-OLT follow-up of 18 months (range = 7-251 months). LB samples (median length = 35 mm) showed graft damage in 28 patients (43%): idiopathic chronic hepatitis (11), steatohepatitis (3), rejection (3), cholangitis (2), and autoimmune/cholestatic recurrence (9). Patients with graft damage had significantly higher serum liver enzyme levels and TE results (median = 7.8 kPa, range = 5.4-27.4 kPa) than the 37 patients without graft damage (median = 5.3 kPa, range = 3.1-7.4 kPa, P < 0.001). By a receiver operating characteristic curve analysis, 2 TE cutoffs for the diagnosis of graft damage were identified: 5.3 kPa with 100% sensitivity and 7.4 kPa with 100% specificity. The pretest probability of graft damage was 43%; in patients with TE values ≤5.3 kPa, the posttest probability of graft damage fell to 0%, but in patients with TE results >7.4 kPa, the posttest probability increased to 100%. In conclusion, the dual TE cutoff allows accurate discrimination between the absence and presence of nonviral liver graft damage and improves the clinical management of OLT recipients in terms of the selection of patients most in need of LB.

Role of lamivudine in the posttransplant prophylaxis of chronic hepatitis B virus and hepatitis delta virus coinfection.

BACKGROUND: Posttransplant combined lamivudine (LAM) and immunoglobulin (HBIg) prophylaxis is the gold standard in the case of single hepatitis B virus (HBV), but is still not recommended in the case of patients coinfected with hepatitis delta virus (HDV). METHODS: We compared two consecutive groups of chronic HDV carriers who survived >6 months after liver transplantation of the risk of recurrence, survival and HBIg requirements: 21 received passive prophylaxis (HBIg group) and 25 were treated with combined prophylaxis (LAM+HBIg group). The immunoprophylaxis schedule was the same in both groups: intramuscular HBIg targeted to maintain anti-HBs levels of >500 IU/L during the first 6 posttransplant months and >200 IU/L thereafter. RESULTS: The mean length of follow-up in the two groups was significantly different (133 vs. 40 months; P<0.001). None of the patients in either group developed recurrent hepatitis, and the 3-year actuarial survival rate was 100% in both groups. During the first 6 months, HBIg requirement was 38% lower in the LAM+HBIg group although similar anti-HBs target levels were maintained, leading to significantly lower costs (5,000 Euros in the first year and 500 Euros in the second). CONCLUSIONS: This is the first study of large and homogeneous cohort of long-term HDV coinfected liver transplant survivors showing the absence of HBV recurrence under combined prophylaxis. Although retrospective, our results suggest that combined anti-HBV prophylaxis should also be preferred to single immunoprophylaxis in patients with HDV coinfection because it allows significant cost savings in the first two posttransplant years.

Feasibility and limits of split liver transplantation from pediatric donors: an italian multicenter experience.

OBJECTIVE: To report the results of a multicenter experience of split liver transplantation (SLT) with pediatric donors. SUMMARY BACKGROUND DATA: There are no reports in the literature regarding pediatric liver splitting; further; the use of donors weighing <40 kg for SLT is currently not recommended. METHODS: From 1997 to 2004, 43 conventional split liver procedures from donors aged <15 years were performed. Nineteen donors weighing < or =40 kg and 24 weighing >40 kg were used. Dimensional matching was based on donor-to-recipient weight ratio (DRWR) for left lateral segment (LLS) and on estimated graft-to-recipient weight ratio (eGRWR) for extended right grafts (ERG). In 3 cases, no recipient was found for an ERG. The celiac trunk was retained with the LLS in all but 1 case. Forty LLSs were transplanted into 39 children, while 39 ERGs were transplanted into 11 children and 28 adults. RESULTS: Two-year patient and graft survival rates were not significantly different between recipients of donors < or =40 kg and >40 kg, between pediatric and adult recipients, and between recipients of LLSs and ERGs. Vascular complication rates were 12% in the < or =40 kg donor group and 6% in the >40 kg donor group (P = not significant). There were no differences in the incidence of other complications. Donor ICU stay >3 days and the use of an interposition arterial graft were associated with an increased risk of graft loss and arterial complications, respectively. CONCLUSIONS: Splitting of pediatric liver grafts is an effective strategy to increase organ availability, but a cautious evaluation of the use of donors < or =40 kg is necessary. Prolonged donor ICU stay is associated with poorer outcomes. The maintenance of the celiac trunk with LLS does not seem detrimental for right-sided grafts, whereas the use of interposition grafts for arterial reconstruction should be avoided.

Split-liver transplantation with pediatric donors: a multicenter experience.

BACKGROUND: Outcomes of split-liver transplantation (SLT) with pediatric donors have never been specifically reported. METHODS: A prospective multicenter study on SLT using donors younger than 15 years was conducted. Thirty-nine split-liver procedures generating a left lateral segment (LLS) and an extended right graft (ERG) were performed. In three cases, no recipient was found for ERG. In all but one case, the celiac trunk was maintained with LLS. Data were available for 67 grafts (90% of the total): 38 LLSs and 9 ERGs transplanted into 46 children and 20 ERGs transplanted into 20 adults. Sixty-two (93%) grafts were used for primary transplants and five (7%) for retransplantation. SLT were performed with 15 donors 10 years of age and less and with 24 between 11 and 15 years. RESULTS: Median follow-up was 24 months. Two-year patient and graft survival were 87% and 82%. Patient and graft survivals were not significantly different between pediatric and adult recipients, between recipients from donors 10 years of age and less and those between 11 and 15 years, and between recipients of LLS and ERG. Arterial complications occurred in 6% of cases (8% in the < or = 10 year donors group, 5% in the 11-15 year donors group). The incidence of other complications was similar between groups. CONCLUSIONS: SLT with pediatric donors, even younger than 10 years, provided results comparable with those achievable using adult donors. The similar incidence of arterial complications among patients receiving LLS or ERG suggests that maintenance of the celiac trunk with LLS is not detrimental for right-sided grafts.

Successful treatment of hemolytic uremic syndrome after liver-kidney transplantation.

INTRODUCTION: Hemolytic-uremic syndrome (HUS) is a rare complication in organ transplantation, characterized by hemolytic microangiopathic anemia, thrombocytopenia, and severe renal failure. The syndrome is a well-recognized complication in bone marrow transplantation, and has been likewise described in several cases of solid organs transplantation, but never in patients receiving combined liver and kidney transplantation. CASE REPORT: We describe a case of HUS in a 59-year-old woman who underwent combined liver-kidney transplantation for hepato-renal polycystic disease. Clinical and laboratory manifestations of the syndrome were severe and included renal failure, hemolytic anemia, severe thrombocytopenia, hypertension, and neurological damage. The initial treatment consisted of withdrawal of cyclosporine, introduction of low-dose tacrolimus, and administration of fresh frozen plasma (FFP) transfusion and heparin. Since there was no improvement in clinical or biochemical features, plasmapheresis with FFP replacement (2000 mL/day) followed by intravenous immunoglobulin (0.4 mg/Kg/day) was started. A rapid improvement in renal function, platelet count, and hemolytic anemia was observed. CONCLUSIONS: Based on the good response observed in our patient, we feel that an aggressive treatment with plasmapheresis and intravenous immunoglobulin should be offered to organ transplant recipients with severe HUS.