Risk Factors for Early Mortality in Liver Transplant Patients.

BACKGROUND: Liver transplantation (LT) is an established treatment for patients with end-stage liver disease. The significant advances in surgical technique, immunosuppression therapy, and anesthesiological management have dramatically improved short- and long-term outcomes. The aim of this study is to correlate specific surgical and anesthesiological variables with causes of early death in LT recipients. METHODS: A retrospective observational analysis of adult patients who underwent LT in the period 2012 to 2016 and died within 90 days following LT was conducted. Exclusion criteria were intraoperative death, split liver, and domino transplant. Death was considered a dependent variable and classified into 3 different groups: death by sepsis, vascular events not related to the graft, and primary non-function. Donor and recipient variables were considered and analyzed using Fisher's exact test. RESULTS: Statistically significative associations (P value < .05) were found between renal function support, retransplantation, and the number of fresh frozen plasma units transfused in one group and early death due to sepsis in the other. CONCLUSIONS: This study identified some risk factors associated with the specific cause of early death in liver transplantation. The clinical implications of these findings are the ability to stratify patients at high risk of early death by planning more intensive and accurate management for them.

Survival benefit of transplantation for recurrence of hepatocellular carcinoma after liver resection.

BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) can be used for tumor recurrence after liver resection (LR) both for initially transplant-eligible patients as conventional salvage therapy (ST) and for non-transplant-eligible patients (beyond Milan criteria) with a goal of downstaging (DW). The aim of this study was to compare the intention-to-treat (ITT) survival rates of patients who are listed for LT, according to these two strategies. METHODS: We analyzed a prospective database of 399 consecutive patients who underwent hepatic resection for HCC from 2002 to 2011 to identify patients included in the waiting list for tumor recurrence. Intention-to-treat (ITT) survivals were compared with those of patients resected for HCC within and beyond Milan criteria in the same period and not included in the LT waiting list. RESULTS: The study group consisted of 42 patients, 28 in the ST group (within Milan) and 14 in the DW group (beyond Milan). The 5-year ITT survival rate was similar between the 2 groups, being 64% for ST and 60% for DW (P=.84). Twenty-five patients (15 ST and 10 DW) underwent LT, 13 (10 ST and 3 DW) were still awaiting LT, 4 (3 ST and 1 DW) dropped out of the waiting list because of tumor progression, and 7 (5 ST [33%] and 2 DW [20%]) had tumor recurrence. The 5-year ITT survival of ST patients was similar to that of 252 in-Milan HCC patients resected only (P=.3), whereas 5-year ITT survival of DW patients was significantly higher (P<.01) than that of 105 beyond-Milan HCC patients resected only. CONCLUSIONS: LR seems to be a safe and effective therapy both as alternative to transplantation and as downstaging strategy for intermediate-advanced HCC. The survival benefit of salvage LT, however, seems to be higher in the 2nd than in the 1st group.

Pain control after liver transplantation surgery.

BACKGROUND: Although post-liver transplantation pain is not as severe as expected from the size of the surgical incision, optimal pain control becomes crucial to aid compliance with the ventilator, improve respiratory function, and facilitate an early weaning from mechanical ventilation. METHODS: Because the majority of analgesics are primarily metabolized and excreted by the hepatobiliary system, a poor recovery of graft function will result in a decrease in clearance and reduced elimination of the drug. On the other hand, if the liver is working well, the metabolism of analgesics improves significantly with minimal accumulation. Morphine-based analgesia has been associated with a higher risk of sedation and respiratory depression compared with major abdominal surgical procedures. Fentanyl and sufentanil in continuous intravenous infusion may be preferred in the presence of hemodynamic instability or bronchospasm. Sufentanil produces shorter-lasting respiratory depression and long-lasting analgesia than does fentanyl. RESULTS: The provision of potent continuous analgesia, independent of the duration of infusion, and the unique pharmacokinetics, not significantly affected by the functional status of the graft, make remifentanil appropriate for the majority of liver-transplanted patients. Unlike for patients with very severe pain after major abdominal surgery, liver transplant recipients usually benefit from tramadol, either in repeated intravenous boluses or continuous intravenous infusion. Paracetamol has been included as adjuvant (or sole agent, rarely) in the analgesic treatment of mild to moderate postoperative pain. The combination treatment (paracetamol plus tramadol) is a reasonable, safe option with improved analgesia and concurrent reduction in the incidence of some opioid-related side effects. CONCLUSIONS: Frequent review of the patient's response is mandatory when potent opioids are used because dose-dependent respiratory depression is a serious and potentially life-threatening adverse effect. The benefits provided by epidural analgesia in this particular setting should be weighed against the risks because in the presence of markedly deranged perioperative blood clotting, the development of epidural hematoma represents a disastrous complication.

Liver autotransplantation for the treatment of unresectable hepatic metastasis: an uncommon indication-a case report.

Ex situ ex vivo liver surgery represents a method to expand the surgical indications to treat otherwise unresectable liver tumors. We report the case of a 38-year old woman with hepatic metastasis from a pancreatoblastoma that was judged to be unresectable due to the involvement of the three hepatic veins. To treat the primary tumor, she underwent a pancreaticoduodenectomy, adjuvant chemotherapy, and thermal ablation of a liver metastasis. After appropriate preoperative study and with the permission of the ethics committee, she underwent ex situ ex vivo liver resection. The hepatectomy was performed by removing the whole liver en bloc with the retrohepatic vena cava. The inferior vena cava was reconstructed by interposition of a prosthetic graft. The ex situ ex vivo hepatic resection, a left hepatic lobectomy included the lesion in segments 1-5-7-8. The two hepatic veins were reconstructed using patches of saphenous vein. The organ was preserved continuously for 6 hours using hypothermic perfusion with 4°C Celsior solution. The liver was then reimplanted performing an anastomosis between the reconstructed hepatic veins and the caval prostheses. The patient was discharged at postoperative day 22 and is currently disease-free at 8 months after surgery and 44 months after the initial diagnosis. Ex situ, ex vivo liver surgery offers an additional option for patients with both primary and secondary liver tumors considered to be unresectable using traditional surgical approaches.

Noninvasive high-frequency percussive ventilation in the prone position after lung transplantation.

Noninvasive positive-pressure ventilation (NIV), which represents a consolidated treatment of both acute and chronic respiratory failure, is increasingly being used to maintain spontaneous ventilation in lung transplant patients with impending pulmonary complications. Adding a noninvasive inspiratory support plus positive end-expiratory pressure (PEEP) has proven to be useful in preventing endotracheal mechanical ventilation, airway injury, and infections. Lung recipients with closure of the small airways in the dependent regions may also benefit from the prone position, which is helpful to promote recruitment of nonaerated alveoli and faster healing of consolidated atelectatic areas. In patients with localized or diffuse lung infiltrates, high-frequency percussive ventilation (HFPV), by either an invasive airway or a facial mask, has been adopted as an alternative ventilatory mode to enhance airway opening, limit potential respirator-associated lung injury, and improve mucus clearance. In nonintubated lung recipients at risk for volubarotrauma with conventional mechanical ventilation, it allows oxygen diffusion into the distal airways at lower mean airway pressures while avoiding repetitive cyclical opening and closing of the terminal airways. We summarize the clinical course of 3 patients with post-lung transplantation respiratory complications who were noninvasively ventilated with HFPV in the prone position. Major advantages of this treatment included gradual improvement of spontaneous clearance of bronchial secretions, significant attenuation of graft infiltrates and consolidations, a reduction in the number of bronchoscopies required, a decrease in spontaneous respiratory rate and work of breathing, and a significant improvement in gas exchange. The patients found HFPV with either standard facial mask or total mask interface to be comfortable or only mildly uncomfortable, and after the sessions they felt more restored. HFPV by facial mask in the prone position may be an interesting and attractive alternative to standard NIV, one that is more useful when implemented before full-blown respiratory failure is established.

Subnormothermic machine perfusion for non-heart-beating donor liver grafts preservation in a Swine model: a new strategy to increase the donor pool?

We previously reported that subnormothermic machine perfusion (sMP; 20°C) is able to improve the preservation of livers obtained from non-heart-beating donors (NHBDs) in rats. We have compared sMP and standard cold storage (CS) to preserve pig livers after 60 minutes of cardiac arrest. In the sMP group livers were perfused for 6 hours with Celsior at 20°C. In the CS group they were stored in Celsior at 4°C for 6 hours as usual. To simulate liver transplantation, both sMP- and CS-preserved livers were reperfused using a mechanical continuous perfusion system with autologus blood for 2 hours at 37°C. At 120 min after reperfusion aspartate aminotransferase levels in sMP versus CS were 499 ± 198 versus 7648 ± 2806 U/L (P < .01); lactate dehydrogenase 1685 ± 418 versus 12998 ± 3039 U/L (P < .01); and lactic acid 4.78 ± 3.02 versus 10.46 ± 1.79 mmol/L (P < .01) respectively. The sMP group showed better histopathologic results with significantly less hepatic damage. This study confirmed that sMP was able to resuscitate liver grafts from large NHBD animals.

Liver transplantation for massive hepatomegaly due to polycystic liver disease: an extreme case.

BACKGROUND: Polycystic liver disease (PLD) is due to a genetic disorder and frequently coexists with polycystic kidney disease (PKD). If the cysts produce symptomatology owing to their number and size, many palliative treatments are available. When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT). CASE REPORT: A 49-year old woman, diagnosed with PLD and PKD, was listed in January 2008 for combined LT and kidney transplantation (KT). A compatible organ became available 8 months later. Despite preserved liver function, the patient's clinical condition was poor; she experienced dyspnea, advanced anorexia, abdominal pain, and severe ascites. At LT, which took 9 hours and was performed using the classic technique, the liver was hard, massive in size (15.5 kg), and not dissociable from the vena cava. The postoperative course was complicated by many septic episodes, the last one being fatal for the patient at 4 months after transplantation. DISCUSSION: LT for PLD in many series shows a high mortality rate. The Model for End-Stage Liver Disease (MELD) score does not stage patients properly, because liver function is usually preserved. The liver can achieve a massive size causing many symptoms, especially malnutrition and ascites; in this setting LT is the only possible treatment. Patients with a low MELD score undergo LT with severe malnutrition that predisposes them to greater susceptibility to sepsis. To identify predictor factors, beyond MELD criteria that relate to the increased liver volume before development of late symptoms is essential to expeditiously treat patients with the poorest prognosis to improve their outcomes.

Microwave thermal ablation for hepatocarcinoma: six liver transplantation cases.

Surgical resection for malignant hepatic tumors, especially hepatocarcinoma (HCC), has been demonstrated to increase overall survival; however, the majority of patients are not suitable for resection. Radiofrequency ablation (RFA) is the most widely used modality for radical treatment of small HCC (<3 cm). It improves 5-year survival compared with standard chemotherapy and chemical ablation, allowing down-staging of unresectable hepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and was recently introduced in the United States of America and Europe with excellent results, especially with regard to large unresectable HCC. Our single-center experience between May 2009 and October 2010 included application of MWA to 154 patients of median age ± standard deviation of 63.5 ± 8.5 years, 6 males, and 1 female, of mean Model for End-Stage Liver Disease (MELD) score (10.1 ± 3.8). The HCC included, hepatitis C virus (HCV)-related (n=70; 45.5%); alcool (ETOH)-related (n=42; 27%), hepatitis B virus (HBV)-related (n=16; 10.5%); and cryptogenic cases (n=26; 17%). The cases were performed for radical treatment down-staging for multifocal pathology or bridging liver transplantation to orthotopic (OLT) in selected patients with single nodules. A computed tomography (CT) scan was performed at 1 month after the surgical procedure to evalue responses to treatment. Among 6 selected patients who underwent OLT; 5 (83.3%) showed disease-free survival at one-year follow-up. The radical treatment achieved no intraoperative evidence of tumor spread or of pathological signs of active HCC among the explanted liver specimens. In conclusion, a MWA seemed to be a safe novel approach to treat HCC and could serve as a "bridge" to OLT and down-staging for patients with HCC.

Neoadjuvant therapy protocol and liver transplantation in combination with pancreatoduodenectomy for the treatment of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis: case report with a more than 8-year disease-free survival.

Cholangiocarcinoma has historically represented a major contraindication to liver transplantation at many centers because of its high recurrence rate and low disease-free survival rate, even after radical surgery. Novel neoadjuvant therapy protocols combined with demolitive surgery and liver transplantation seem to achieve successful results in terms of overall and disease-free survivals. Surgery frequently seems to be unsatisfactory only for patients also suffering from chronic cirrhosis or end-stage liver disease. We have reported a case of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis treated with neoadjuvant radiochemotherapy and endoscopic brachytherapy, followed by liver transplantation combined with pancreatoduodenectomy, who has survived free of disease for >8 years.

Diverting loop ileostomy after restorative proctocolectomy: predictors of poor outcome and poor quality of life.

AIM: Diverting loop ileostomy is used to minimize the impact of anastomotic complication after restorative proctocolectomy (RPC). However, the ileostomy itself may have complications and therefore affect quality of life (QOL). The aim of this study was to analyse the predictors of complications of the ileostomy formation and closure and of the QOL of these patients. METHOD: Forty-four consecutive patients who underwent RPC were enrolled. Records of the ileostomy follow-up were retrieved from a prospectively collected database and QOL was assessed with the Stoma-QOL questionnaire. Ileostomy site coordinates were measured. Univariate and multivariate analysis were performed. RESULTS: In this series, three patients experienced peristomal herniae, two ileostomy stenosis, seven ileostomy retraction and fourteen peristomal dermatitis. Emergency surgery was the only predictor of parastomal hernia (P = 0.017). Stenosis correlated with the distance from the umbilicus (tau = 0.24, P = 0.021). Use of standard rod and retraction were independent predictors of peristomal dermatitis (P = 0.049 and P = 0.001). Stoma-QOL was directly correlated to the age of the patients and to the occurrence of parastomal hernia (P = 0.001 and P = 0.021, respectively). After stoma closure, two patients reported wound sepsis and seven suffered obstructive episodes. CONCLUSION: The predictors of negative outcome after construction of a diverting loop ileostomy after RPC were urgent surgery, use of standard rod, the distance of the stoma site from the umbilicus, parastomal herniae and the older age of patients.