Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model

BACKGROUND Although the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)induces more rapid liver regeneration than portal vein embolization,the mechanism remains unclear.AIM To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase(eNOS)activation on liver regeneration in ALPPS.METHODS The future liver remnant/body weight(FLR/BW)ratio,hepatocyte proliferation,inflammatory cytokine expression,and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation(PVL)models.Hepatocyte proliferation was assessed based on Ki-67 expression,which was confirmed using immunohistochemistry.The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays.The Akt-eNOS pathway was assessed using western blotting.To explore the role of inflammatory cytokines and NO,Kupffer cell inhibitor gadolinium chloride(GdCl3),NOS inhibitor N-nitro-arginine methyl ester(L-NAME),and NO enhancer molsidomine were administered intraperitoneally.RESULTS The ALPPS group showed significant FLR regeneration(FLR/BW:1.60%±0.08%,P<0.05)compared with that observed in the PVL group(1.33%±0.11%)48 h after surgery.In the ALPPS group,serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group.However,the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3(1.72%±0.19%,P<0.05;22.25%±1.30%,P<0.05)than in the PVL group(1.33%±0.11%and 12.78%±1.55%,respectively).Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group.There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index.In the PVL group treated with molsidomine,the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.CONCLUSION Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS,whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.

Small-for-size syndrome in liver transplantation:Definition,pathophysiology and management

Background:Since the first success in an adult patient,living donor liver transplantation(LDLT)has become an universally used procedure.Small-for-size syndrome(SFSS)is a well-known complication after partial LT,especially in cases of adult-to-adult LDLT.The definition of SFSS slightly varies among transplant physicians.The use of a partial liver graft has risks of SFSS development.Persistent portal vein(PV)hypertension and PV hyper-perfusion after LT were identified as the main factors.Hence,various approaches were explored to modulate PV flow and decrease PV pressure in order to alleviate this syndrome.Herein,the definition,clinical symptoms,pathophysiology,basic research,as well as preventive and treatment strategies for SFSS are reviewed based on an extensive review of the literature and on our own experiences.Data sources:The articles were collected through PubMed using search terms“liver transplantation”,“living donor liver transplantation”,“living liver donation”,“partial graft”,“small-for-size graft”,“small-forsize syndrome”,“graft volume”,“remnant liver”,“standard liver volume”,“graft to recipient body weight ratio”,“sarcopenia”,“porcine”,“swine”,and“rat”.English publications published before March 31,2020 were included in this review.Results:Many transplant surgeons performed PV flow modulation,including portocaval shunt,splenic artery ligation and splenectomy.With these techniques,patient outcome has been improved even when using a"small"graft.Other factors,such as preoperative recipients’nutritional and skeletal muscle status,graft congestion,and donor factors,were also identified as risk factors which all have been addressed using various strategies.Conclusions:The surgical approach controlling PV flow and pressure could help to prevent SFSS especially in severely ill recipients.In the absence of efficacious medications to resolve SFSS,conservative treatments,including aggressive fluid balance correction for massive ascites,anti-microbiological therapy to prevent or control sepsis and intensive nutritional therapy,are all required if SFSS could not be prevented.

Gallbladder Burkitt's lymphoma mimicking gallbladder cancer:A case report

BACKGROUND Malignant lymphoma is a rare form of gallbladder malignancy.Most of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas;however,Burkitt’s lymphoma of the gallbladder is extremely rare,and only two previous reports are available in the literature.Herein,we report a rare case of Burkitt’s lymphoma of the gallbladder mimicking gallbladder adenocarcinoma.CASE SUMMARY An 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography(CT)performed for hypertension screening.His laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 receptor.Imaging examinations revealed two irregular and contrastenhanced masses extending into the gallbladder lumen,but these did not infiltrate the serosa.Moreover,a periportal lymph node had enlarged to 30 mm.Based on these findings,we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis,which was treated using bile duct resection with gallbladder bed resection and periportal lymph node dissection.However,the patient was finally diagnosed as having Burkitt’s lymphoma.Although the surgical margin was pathologically negative,recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after discharge.Thus,he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide,doxorubicin,vincristine,and prednisone.CONCLUSION Burkitt’s lymphoma can occur in the gallbladder.Biopsy can be useful in cases with findings suggestive of gallbladder malignant lymphoma.