Identification of new donor variables associated with graft survival in a single-center liver transplant cohort.

We currently face the more widespread use of marginal livers for organ transplantation. Therefore, it is imperative to adequately identify the factors affecting early and late graft survival in that setting. The objective of this study was to determine the donor variables associated with graft survival in the liver transplant program of the University of Montreal. We retrospectively studied the survival of 634 grafts transplanted into 634 recipients between 1990 and 2008. The variables associated with 1- and 5-year graft survival were identified with the Cox proportional hazards regression model. The donor population was characterized by a mean age of 45.24 ± 18.15 years; 52.8% had at least 1 of the currently recognized extended criteria donor factors. The recipients had a mean age of 52.51 ± 10.80 years and a mean Child-Pugh score of 9.58 ± 2.32. Liver grafts were considered inadequate with respect to their gross appearance in 16 cases (2.5%). The 1- and 5-year graft survival rates were 78.7% and 71.1%, respectively. According to a Cox regression multivariate analysis, the independent determining factors associated with graft survival were (1) the graft appearance (P < 0.001 at 1 and 5 years), (2) the donor partial pressure of oxygen/fraction of inspired oxygen ratio (P = 0.005 at 1 year and P < 0.005 at 5 years), and (3) the donor hemoglobin level (P = 0.008 at 1 year and P = 0.005 at 5 years). In conclusion, the gross graft appearance, the presence of donor lung diffusion abnormalities, and the donor hemoglobin levels were significantly associated with graft survival. These observations, if they are confirmed, could improve our ability to select marginal organs.

Hypertrophy of the non-embolized liver after chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NC(+)) and portal vein embolization (PVE) enables curative resection in more patients with colorectal-liver metastases (CRLM). However, after NC(+), structural alterations have been reported with the risk of post-operative hepatic failure. We undertook to determine if NC(+) toxicity limits future remnant liver (FRL) hypertrophy after PVE. METHODS: PVE was performed in 20 patients, 13 (65%) of whom previously received a mean FOLFIRI (5-fluorouracil + leucovorin + irinotecan) regimen (NC(+)) of 6.6 cycles. The seven remaining patients served as the control group without NC (NC(-)). RESULTS: CRLM were bilateral in 69% (NC(+)) and 57% (NC(-)), and synchronous in 84% (NC(+)) and 14% (NC(-)). The FRL hypertrophy rate was 54.1% (NC(+)) and 43.7% (NC(-)) (P= 0.3). CRLM were unresectable in four of our 20 patients, i.e. group NC(+): one insufficient FRL hypertrophy and one severe steatosis; and group NC(-): two tumoral progressions. In both groups, the operative parameters were comparable except for pedicular clamping: 8 (NC(+)) and 36 min (NC(-)), respectively (P < 0.05). Also, the surgical outcome rate and hospital stay were comparable. No significant pathological difference was observed between the two groups. No mortality occurred in either group. CONCLUSION: In view of our limited experience, we conclude that hypertrophy of the non-embolized liver (FRL) is not altered after FOLFIRI-based NC.

Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia.

OBJECTIVE: To determine precisely the role of parathyroid hormone (PTH) and of phosphatonins in the genesis of posthepatectomy hypophosphatemia. BACKGROUND: Posthepatectomy hypophosphatemia has recently been related to increased renal fractional excretion of phosphate (FE P). To address the cause of hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins, and the number of removed hepatic segment in patients with this disorder. METHODS: Serum phosphate (PO4), ionized calcium (Ca++), HCO3-, pH and FE P, intact PTH (I-PTH), carboxyl-terminal fibroblast growth factor 23 (C-FGF-23) and intact fibroblast growth factor 23 (I-FGF-23), FGF-7, and secreted frizzled related-protein-4 (sFRP-4) were measured before and on postoperative (po) days 1, 2, 3, 5, and 7, in 18 patients undergoing liver resection. The number of removed hepatic segments was also assessed. RESULTS: Serum PO4 concentrations decreased within 24 hours, were lowest (0.66 +/- 0.03 mmol/L; P < 0.001) at 48 hours, and returned to normal within 5 days of the procedure. FE P peaked at 25.07% +/- 2.26% on po day 1 (P < 0.05). Decreased ionized calcium concentrations (1.10 +/- 0.01 mmol/L; P < 0.01) were observed on po day 1 and were negatively correlated with increased I-PTH concentrations (8.8 +/- 0.9 pmol/L; P < 0.01; correlation: r = -0.062, P = 0.016). FE P was positively related to I-PTH levels on po day 1 (r = 0.52, P = 0.047) and negatively related to PO4 concentrations (r = -0.56, P = 0.024). Severe hypophosphatemia and increased urinary phosphate excretion persisted for 72 hours even when I-PTH concentrations had returned to normal. I-FGF-23 decreased to its nadir of 7.8 +/- 6.9 pg/mL (P < 0.001) on po day 3 and was correlated with PO4 levels on po days 0, 3, 5, and 7 (P < 0.001). C-FGF-23, FGF-7 and sFRP-4 levels could not be related to either PO4 concentrations or FE P. CONCLUSION: Posthepatectomy hypophosphatemia is associated with increased FE P unrelated to I-FGF-23 or C-FGF-23, FGF-7, or sFRP-4. I-PTH contributes to excessive FE P partially on po day 1 but not thereafter. Other yet defined factors should explain post hepatectomy hypophosphatemia.

Carcinoid tumor of the common bile duct: a rare complication of von Hippel-Lindau syndrome.

Von Hippel-Lindau syndrome (VHL) is a rare autosomal-dominant, inherited familial cancer syndrome. Hemangioblastomas, pheochromocytomas and renal carcinoma are the frequent reported VHL tumors. Neuroendocrine tumors have also been described, mostly in the pancreas and rarely in the biliary trees. We report the second case of bile duct carcinoid in a 31-year-old VHL woman. She underwent right adrenalectomy for a pheochromocytoma in the past. She also had a positive family history of phenotypic expression of VHL syndrome. The patient presented with biliary colic. Endoscopic retrograde cholangio-pancreatography showed intra-luminal bile duct mass. Surgical exploration identified a beige nodular lesion that was a carcinoid tumor on histology. This new association should be clarified by further genetic investigations.

Reuse of liver graft from a brain dead recipient.

BACKGROUND: Brain death in fulminant hepatic failure (FHF) is a rare occurrence after successful orthotopic liver transplantation (OLT). Reuse of the liver graft may be considered. We report a successful OLT using such an organ in a 62-yr-old man with hematochromatosis-related cirrhosis and hepatocellular carcinoma. METHODS: Liver donor was 56-yr-old man with normal liver function tests. First recipient was a 26-yr-old woman with an acetaminophen-induced FHF. Before OLT, she developed progressive coma without obvious cerebral edema on the cerebral CT-scan. The transplantation proceeded as planned and was uneventful. However, patient exhibited bilateral non-reactive mydriasis during postoperative hours and was declared brain dead. Transplanted liver was functioning adequately. Its reuse was discussed with her family and the second recipient. After informed consent, the transplanted liver and heart were harvested. First and second liver cold ischemia times were 10 h and 75 min, respectively. RESULTS: Second recipient recovered uneventful and discharged 23 d after OLT. Liver function is still normal 30 months after OLT without rejection or hepatocellular carcinoma recurrence. CONCLUSION: Even after OLT, brain death remains possible in FHF. In absence of contraindications, reuse of transplanted liver allows for a rational use of already rare liver grafts.