We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy (FAP) and liver dysfunction.A two-stage surgical plan was designed, and one domino graft was implanted during each stage.During the first CASE
The Chamdo Basin is a secondary basin in the eastern part of Tibet China and is one of the most promising of petroliferous basins for new petroleum exploration. The Qamdo Basin records a complex burial history from the Mesozoic to the Cenozoic; however, the poorly constrained sedimentology of Cenozoic strata in this basin has severely obscured the overall profile and impeded further explorations of oil and gas resources. Here, we conduct whole-rock geochemical analyses of major, trace, and rare earth elements in fine-grained clastic rocks of the Paleocene Gongjue Formation, Qamdo Basin to reveal depositional environments, provenance, and tectonic setting. Petrologically, the Gongjue Formation is dominated by red fine-grained sandy mudstones/siltstones with ripple marks. The high values of the chemical index of alteration (avg. of 78.93), chemical index of weathering (avg. of 90.10), and index of compositional variability (avg. of 2.5) suggest that the basin has undergone heavy weathering. Cross-plots of La vs Th, Th vs Sc vs Zr/10, and Th vs Co vs Zr/10 reveal a continental arc tectonic setting. Paleosalinity (Sr/Ba), paleoclimate (Sr/Cu), and redox proxies (V/Cr, U/Th, and enrichment factors of Mo and U) indicate brackish to saline and oxidizing paleowater masses during deposition of the Gongjue Formation. Provenance analyses via elements and petrology reveal that sediments in the Gongjue Formation are mainly derived from intermediate-acidic rocks of the upper crust. We conclude that the first and third members are more arid climate and heavily chemically weathered than the second member. In combination with previous studies of the structural evolution of the Qamdo Basin since the Paleogene, a model is built to describe the sedimentary environment and evolution of the Qamdo Basin during transition to the Paleocene. The first and third members, i.e., the Eg1 and Eg3 members of the Gongjue Formation, are dominated by an oxidizing environment of seawater-saltwater, and the climate ranges from warm and humid to arid and hot, with relatively stable environmental changes. The Eg2 member of the Gongjue Formation is dominated by an oxidizing environment of seawater-saltwater, and the climate ranges from warm and humid to arid and hot, with more frequent environmental evolution. Our model aids in better understanding of the Paleocene climate evolution of the eastern Tibetan Plateau.
Hyperhomocysteinemia, resulting from a cystathionine beta synthase (CBS) deficiency, is an autosomal recessive disease associated with high levels of homocysteine. Such patients can present with severe mental retardation, ectopia lentis and osteoporosis and thromboembolic disease. To the best of our knowledge, only two cases of liver transplantation for CBS deficiency have been published. Here, we report a case of an 8-year-old male with a CBS deficiency that underwent living donor liver transplantation. The postoperative course was uneventful and homocysteine levels remained normal. The liver of this CBS deficiency patient was then successfully used in domino transplantation. The domino liver transplantation recipient was a 41-year-old male diagnosed with acute liver failure following hemi-liver resection due to cholangiocarcinoma. The domino recipient developed acquired hyperhomocysteinemia, which was controlled with a special regimen of medications. No complications relative to CBS deficiency were observed up to 11 months post-transplant. At this time, the patient expired as a result of cholangiocarcinoma recurrence. In conclusion, our data suggest that liver transplantation for CBS deficiency can be effective, safe and beneficial. It is possible to be both safe and beneficial to use a CBS deficiency patient as a domino donor for salvage liver transplantation in a selective category of recipients.
Although orthotopic liver transplantation remains the only proven treatment for end-stage liver disease and inherited metabolic liver disease, its application has been limited by the scarcity of donor organs available for transplantation. Among feasible approaches developed to expand the donor organ pool, domino liver transplantation is a strategy in which explanted genetically defective livers of liver transplant recipients are used as grafts in other patients. Another promising therapeutic strategy is hepatocyte transplantation, an alternative to liver transplantation for certain groups of patients. However, the availability of primary hepatocytes is also hindered by the shortage of donor liver tissues. Against this background, domino hepatocyte transplantation, a strategy that utilizes the hepatocytes derived from the explanted livers of liver transplant recipients with noncirrhotic inherited metabolic liver diseases as the source of primary hepatocytes, may help increase the supply of liver cells available for transplantation. In this review, we focus on the status quo of domino liver transplantation and domino hepatocyte transplantation. We also describe recent innovative transplant strategies based on domino transplantation.
Abstract As one of the most malignant cancer types, hepatocellular carcinoma (HCC) is highly invasive and capable of metastasizing to distant organs. Intermedin (IMD), an endogenous peptide belonging to the calcitonin family, has been suggested playing important roles in cancer cell survival and invasion, including in HCC. However, how IMD affects the behavior of HCC cells and the underlying mechanisms have not been fully elucidated. Here, we show that IMD maintains an important homeostatic state by activating the ERK1/2-EGR1 (early growth response 1) signaling cascade, through which HCC cells acquire a highly invasive ability via significantly enhanced filopodia formation. The inhibition of IMD blocks the phosphorylation of ERK1/2, resulting in EGR1 downregulation and endoplasmic reticulum stress (ER) stress, which is evidenced by the upregulation of ER stress marker DDIT3 (DNA damage-inducible transcript 3). The high level of DDIT3 induces HCC cells into an ER-stress related apoptotic pathway. Along with our previous finding that IMD plays critical roles in the vascular remodeling process that improves tumor blood perfusion, IMD may facilitate the acquisition of increased invasive abilities and a survival benefit by HCC cells, and it is easier for HCC cells to obtain blood supply via the vascular remodeling activities of IMD. According to these results, blockade of IMD activity may have therapeutic potential in the treatment of HCC.
Background Ethylmalonic encephalopathy (EE) is a rare autosomal recessive metabolic disorder caused by impaired mitochondrial sulfur dioxygenase. Due to poor therapeutic effect of current conventional treatments, progressive psychomotor regression and neurological impairment usually contribute to early death in the first decade of life. Liver transplantation (LT) is emerging as a novel therapeutic option for EE; however, worldwide experience is still limited. Case summary An 18-mo-old patient with the diagnosis of EE received a living donor liver transplant in our institution, which, to our knowledge, is the first case in Asian-Pacific countries. During 20 mo of follow-up, the longitudinal metabolic evaluations revealed a wild fluctuation in urinary EMA levels, still far beyond the normal range. Urinary 2-methylsuccinic acid levels gradually restored to normal, whereas the concentrations of urinary isobutyrylglycine and plasma C4- and C5-acylcarnitines fluctuated markedly and still remained above the reference limits. Only mild amelioration of petechiae and ecchymosis was observed, and no dramatic reversion of chronic mucoid diarrhea and orthostatic acrocyanosis occurred. Although brain magnetic resonance imaging suggested a certain improvement in basal ganglia lesions, the patient still presented developmental delay and neurologic disability. Conclusion LT may bring about a partial but not complete cure to EE. Given its definite role in defending against the devastating natural progression of EE, LT should still be considered for patients with EE in the absence of other superior therapeutic options. Early establishment of diagnosis and initiation of conventional treatment pre-transplant, timely LT, and continuous administration of metabolism-correcting medications post-transplant may be helpful in minimizing the neurologic impairment and maximizing the therapeutic value of LT in EE.
The aim of the present study was to quantitatively monitor the response of CD95 molecules expressed on CD3(+) T cells (CD95(+)CD3(+) cells) and CD38 molecules expressed on CD8(+) T cells (CD38(+)CD8(+) cells) to ganciclovir treatment after orthotopic liver transplant (OLT) in recipients with active human cytomegalovirus (HCMV) infection.Blood samples were collected from 20 liver transplanted recipients with active HCMV infection and 24 recipients without HCMV infection. CD95(+)CD3(+) cells and CD38(+)CD8(+) cells were quantitatively detected with QuantiBRITE bead methods by dual-color flow cytometry analysis during the post-transplantation period.CD95(+)CD3(+) cells and CD38(+)CD8(+) cells were not significantly different among different ages of healthy adults (P > 0.05). CD95(+)CD3(+) cells and CD38(+)CD8(+) cells were drastically increased in the active HCMV infection group compared with that in the stable group or in the healthy group (P < 0.001), and then they were gradually decreased within the next several weeks after ganciclovir treatment when compared with active HCMV infection recipients (P < 0.001).The present study showed that CD38(+)CD8(+) T cells can be an appropriate immunological marker for early detection and antiviral therapeutic monitoring of HCMV infection. The evaluation of CD95 molecule levels may be used routinely in clinical practice to assess the level of immunosuppression.
To assess the efficacy and safety of balloon dilatation for the treatment of hepatic venous outflow obstruction (HVOO) following pediatric liver transplantation.A total of 246 pediatric patients underwent liver transplantation at our hospital between June 2013 and September 2016. Among these patients, five were ultimately diagnosed with HVOO. Seven procedures (two patients underwent two balloon dilatation procedures) were included in this analysis. The demographic data, types of donor and liver transplant, interventional examination and therapeutic outcomes of these five children were analyzed. The median interval time between pediatric liver transplantation and balloon dilatation procedures was 9.8 mo (range: 1-32).Five children with HVOO were successfully treated by balloon angioplasty without stent placement, with seven procedures performed for six stenotic lesions. All children underwent successful percutaneous intervention. Among these five patients, four were treated by single balloon angioplasty, and these patients did not develop recurrent stenosis. In seven episodes of balloon angioplasty across the stenosis, the pressure gradient was 12.0 ± 8.8 mmHg before balloon dilatation and 1.1 ± 1.5 mmHg after the procedures, which revealed a statistically significant reduction (P < 0.05). The overall technical success rate among these seven procedures was 100% (7/7), and clinical success was achieved in all five patients (100%). The patients were followed for 4-33 mo (median: 15 mo). No significant procedural complications or procedure-related deaths occurred.Balloon dilatation is an effective and safe therapeutic option for HVOO in children undergoing pediatric liver transplantation. Venous angioplasty is also recommended in cases with recurrent HVOO.
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