Predictive Index for Tumor Recurrence after Liver Transplantation for Locally Advanced Intrahepatic and Hilar Cholangiocarcinoma

AbstractTumor recurrence is the major obstacle for pushing the envelope of liver transplantation for hepatocellular carcinoma (HCC) patients. The inflammatory cascades activated by acute liver graft injury promote tumor recurrence. We aimed to explore the role and mechanism of myeloid-derived suppressor cell (MDSC) mobilization induced by liver graft injury on tumor recurrence. By analyzing 331 HCC patients who received liver transplantation, the patients with graft weight ratio (GWR, the weight of liver graft divided by the estimated standard liver weight of recipient) <60% had higher tumor recurrence than GWR ≥60% ones. MDSCs and CXCL10/TLR4 levels were significantly increased in patients with GWR <60% or tumor recurrence. These findings were further validated in our rat orthotopic liver transplantation model. In CXCL10−/− and TLR4−/− mice of hepatic ischemia/reperfusion injury plus major hepatectomy (IRH) model, monocytic MDSCs, instead of granulocytic MDSCs, were significantly decreased. Importantly, CXCL10 deficiency reduced the accumulation of TLR4+ monocytic MDSCs, and CXCL10 increased MDSC mobilization in the presence of TLR4. Moreover, MMP14 was identified as the key molecule bridging CXCL10/TLR4 signaling and MDSC mobilization. Knockout or inhibition of CXCL10/TLR4 signaling significantly reduced the tumor growth with decreased monocytic MDSCs and MMP14 in the mouse tumor recurrent model. Our data indicated that monocytic MDSCs were mobilized and recruited to liver graft during acute phase injury, and to promote HCC recurrence after transplantation. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent the therapeutic potential in decreasing post-transplant liver tumor recurrence.

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Downstaging Locally Advanced Cholangiocarcinoma Pre-Liver Transplantation: A Prospective Pilot Study

Journal of Surgical Research ◽

10.1016/j.jss.2019.04.023 ◽

2019 ◽

Vol 242 ◽

pp. 23-30 ◽

Cited By ~ 4

Author(s):

Melissa Wong ◽

Joohyun Kim ◽

Ben George ◽

Calvin Eriksen ◽

Terra Pearson ◽

...

Keyword(s):

Liver Transplantation ◽

Pilot Study ◽

Locally Advanced ◽

Prospective Pilot Study

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Incidence, Characteristics, and Prognosis of Incidentally Discovered Hepatocellular Carcinoma after Liver Transplantation

Journal of Transplantation ◽

10.1155/2016/1916387 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Walid El Moghazy ◽

Samy Kashkoush ◽

Glenda Meeberg ◽

Norman Kneteman

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Tumor Recurrence ◽

Patient Survival ◽

Steady Increase ◽

Liver Transplants ◽

Significant Difference ◽

One Year ◽

Over Time

Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants.Methods.We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma.Results.Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P<0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P=0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P=0.016).Conclusions.iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC.

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