Umberto Montin

Growth hormone/insulin-like growth factor 1 axis recovery after liver transplantation: A preliminary prospective study

Many studies on cirrhotic patients have shown that insulin‐like growth factor 1 (IGF‐1) plasma levels are related to the severity of liver dysfunction. This result suggests that IGF‐1 is probably useful for monitoring liver function in the perioperative course of orthotopic liver transplantation (OLT). Growth hormone (GH), IGF‐1 plasma levels, and routine liver function tests were measured in 15 adult cirrhotic patients undergoing OLT. Measurements were made at the beginning of the operation; during OLT; 24 hours after reperfusion; and in the morning on days 7, 30, and 90. Twenty age‐matched healthy volunteers with normal liver function served as controls. The study group had significantly higher GH levels and lower IGF‐1 levels in the preoperative period compared with the controls. All patients achieved a complete functional hepatic recovery 1 month after OLT, although in 6 of them, the graft had an initial poor function (Group‐IPF). GH and IGF‐1 levels achieved near normal range within 1 week after OLT, and they had no significant correlations with other routine biochemistry tests in this period. IGF‐1 levels in Group‐IPF rose more slowly than in the group with a normal recovery of graft function. Surprisingly, 24 hours after reperfusion, IGF‐1 levels were higher in Group‐IPF than in the group with normal graft function. In conclusion, the severe GH/IGF‐1 axis impairment found in patients with end‐stage cirrhosis reverted very rapidly in the first days after successful OLT. Such a quick, postoperative modulation of IGF‐1 plasma level by the graft suggests that this hormone has the potential to become one of the early indicators of post‐OLT liver function recovery. (Liver Transpl 2004;10:692–698.)

Epithelial to mesenchymal transition in the liver field: the double face of Everolimus in vitro

BackgroundEverolimus (EVE), a mammalian target of rapamycin inhibitor, has been proposed as liver transplant immunosuppressive drug, gaining wide interest also for the treatment of cancer. Although an appropriate tolerance, it may induce several adverse effects, such as fibro-interstitial pneumonitis due to the acquisition of activated myofibroblasts. The exact molecular mechanism associated with epithelial to mesenchymal transition (EMT) may be crucial also in the liver context. This work examines the role and the molecular mediators of EMT in hepatic stellate cell (HSC) and human liver cancer cells (HepG2) and the potential role of EVE to maintain the epithelial phenotype rather than to act as a potential initiators of EMT.MethodsReal time-PCR and western blot have been used to assess the capability of EVE at low-therapeutic (10 nM) and high (100 nM) dose to induce an in vitro EMT in HSC and HepG2.ResultsBiomolecular experiments demonstrated that low concentration of EVE (10 nM) did not modify the gene expression of alpha-smooth muscle actin (α-SMA), Vimentin (VIM), Fibronectin (FN) in both HSC and HepG2 cells, whereas EVE at 100 nM induced a significant over-expression of all the three above-mentioned genes and an increment of α-SMA and FN protein levels. Additionally, 100 nM of EVE induced a significant phosphorylation of AKT and an up-regulation of TGF-β expression in HSC and HepG2 cells.DiscussionOur data, although obtained in an in vitro model, revealed, for the first time, that high concentration of EVE may induce EMT in liver cells confirming previous published evidences obtained in renal cells. Additionally, they suggested that mTOR-I should be administered at the lowest dose able to maximize their important and specific therapeutic properties minimizing or avoiding fibrosis-related adverse effects.ConclusionsIn summary, if confirmed by additional studies, our results could be useful for researchers to standardize new therapeutic immunosuppressive and anticancer drugs protocols.

Syngeneic living-donor liver transplantation for hemangioendothelioma: a clinical model for studying liver regeneration.

A 22‐year‐old Caucasian patient underwent living‐donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipients graft increased much more than the donors residual liver in the first postoperative month (1.6‐fold vs. 1.2‐fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin‐like growth factor 1 (IGF‐1), insulin‐like growth factor 2 (IGF‐2) and insulin‐like growth factor binding protein 3 (IGFBP‐3) values than the recipient on postoperative days (POD) 3–30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis α, interleukin 6 (IL‐6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH‐hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Liver Metastases From Renal Oncocytoma With Vascular Extension

The 2016 World Health Organization Renal Tumor Classification defines renal oncocytoma (RO) as a benign epithelial tumor; however, malignant histopathologic features have been documented. Rare cases with metastases have been reported. We describe the case of a 62-year-old woman who was referred to the Urology Clinic for a routine work-up. Magnetic resonance imaging and computerized tomography showed a 7-cm mass in the middle and lower portions of the left kidney and 2 suspected liver metastases. The patient underwent surgery. Microscopically both renal and liver lesions presented solid, solid-nested, and microcystic architecture, composed predominantly of large eosinophilic cells without any worrisome pattern except the vascular extension. The cells were positive for S100A1, CD117, and PAX-8 and negative for CAIX, CK7, and AMACR. Fluorescence in situ hybridization showed a disomic profile for the chromosomes 1, 2, 6, 7, 10, 17. No mutation of coding sequence of the SDHB, SDHC, SDHD, VHL, and BHD genes and no loss of heterozygosity at 3p were found. The final diagnosis was “RO” according to the 2016 World Health Organization Renal Tumor Classification with “liver metastases.” This report provides a wide clinical-pathologic, immunophenotypical and molecular documentation of a RO with liver metastases.

Rapid screening for malignancy in organ donors: 15-year experience with the Verona “Alert” protocol and review of the literature

Prevention of transmission of malignancy from donors to recipients is an aim of donor assessment. We report the most stringent interpretation of the Italian National Guidelines.

Multidrug-resistant Combined Infections in a Liver Transplanted Patient: Case Report.

We report a case of successfully treated multiple liver abscesses in a liver-transplanted patient, sustained by combined multidrug-resistant infections. Two months after a liver transplant, a computed tomography scan revealed the presence of multiple abscesses in the liver graft. Blood cultures and abscessual liver fluid were both positive for acquired colistin- and carbapenem- resistant Klebsiella pneumoniae and an extended-spectrum of beta-lactamases-producing Enterobacter aerogenes. The treatment strategy consisted of different prolonged antimicrobial combinations and draining of the abscesses with complete recovery of the liver lesions.