Emir Hoti

Prospective evaluation of the prognostic scores for cirrhotic patients admitted to an Intensive Care Unit

BACKGROUND & AIMS Cirrhotic patients admitted to an Intensive Care Unit (ICU) have a poor prognosis. Identifying patients in whom ICU care will be useful can be challenging. The aim of this study was to assess the predictive value of prognostic scores with respect to mortality and to identify mortality risk factors. METHODS Three hundred and seventy-seven cirrhotic patients admitted to a Liver ICU between May 2005 and March 2009 were enrolled in this study. Their average age was 55.5±11.4 years. The etiology of cirrhosis was alcohol (68%), virus hepatitis (18%), or mixed (5.5%). The main causes of hospitalization were gastrointestinal hemorrhage (43%), sepsis (19%), and hepatic encephalopathy (12%). RESULTS ICU and in-hospital mortality rates were 34.7% and 43.0%, respectively. Infection was the major cause of death (81.6%). ROC curve analysis demonstrated that SOFA (0.92) and SAPS II (0.89) scores calculated within 24h of admission predicted ICU mortality better than the Child-Pugh score (0.79) or MELD scores with (0.79-0.82) or without the incorporation of serum sodium levels (0.82). Statistical analysis showed that the prognostic severity scores, organ replacement therapy, and infection were accurate predictors of mortality. On multivariate analysis, mechanical ventilation, vasopressor therapy, bilirubin level at admission, and infection were independently associated with ICU mortality. CONCLUSIONS For cirrhotic patients admitted to the ICU, SAPS II, and SOFA scores predicted ICU mortality better than liver-specific scores. Mechanical ventilation or vasopressor therapy, bilirubin levels at admission and infection in patients with advanced cirrhosis were associated with a poor outcome.

Pulmonary complications after elective liver transplantation-incidence, risk factors, and outcome.

&NA; After liver transplantation (LT), postoperative pulmonary complications (PPC) occur in approximately 35% to 50% of the recipients. Among these PPC, pneumonia is the most frequently encountered. Pulmonary dysfunction has also been widely reported among patients awaiting LT. The links between this dysfunction and PPC have not been clearly established. In this present cohort study, we evaluated the incidence and profile of post-LT pneumonia and identified potential preoperative risk factors. Methods The postoperative clinical course of 212 liver transplant recipients between January 2008 and April 2010 was analyzed. These patients were treated in a single intensive care unit and received standardized postoperative care. Results During the postoperative period, 47 (22%) patients developed pneumonia, of whom 20 (43%) developed respiratory failure requiring mechanical ventilation. Univariate analysis showed that several preoperative factors (age of recipient, model for end-stage liver disease score, indication for LT, platelet count, and restrictive lung pattern revealed by preoperative pulmonary function tests) and the transfusion (blood units and fresh frozen plasma units) during the operative period were associated with pneumonia. Using multivariate analysis by logistic regression, only a restrictive lung pattern (odds ratio=3.14; 95% confidence interval, 1.51–6.51; P=0.002) and the international normalized ratio measured prior LT (OR=4.95; 95% confidence interval, 1.86–8.59; P=0.0004) were independent predictors of pneumonia after LT. Conclusion Pneumonia is common among patients undergoing LT and is a major cause of morbidity. A restrictive pattern on preoperative pulmonary testing and a higher international normalized ratio measured prior LT were associated with more risk of postoperative pneumonia.

Caval inflow to the graft for liver transplantation in patients with diffuse portal vein thrombosis: a 12-year experience.

Objective:To analyze the short- and long-term results of cavoportal anastomosis (CPA) and renoportal anastomosis (RPA) in 20 consecutive liver transplantation (LT) candidates with diffuse portal vein thrombosis (PVT). Summary Background Data:Caval inflow to the graft (CIG) by CPA or RPA has been the most commonly used salvage technique to overcome the absolute contraindication for LT in case of diffuse PVT. Methods:From 1996 to 2009, 3 patients (15%) underwent CPA and 17 patients (85%) had an RPA during LT. In addition to routine follow-up, patients were specifically evaluated for signs of portal hypertension (PHT) and for patency of the anastomoses. The follow-up ranged from 3 months to 12 years (median of 4.5 years). Results:Caval inflow to the graft was feasible in all attempted cases. In the short term (<6 months), 35% of patients had residual PHT-related complications (massive ascites and variceal bleeding). These resolved spontaneously or with endoscopic management. Three deaths occurred; none was related to PHT or shunt thrombosis. In the long term (>6 months), 1 death occurred because of recurrent variceal bleeding after RPA thrombosis. At last follow-up, all living patients [n = 13 (65%)] had normal liver function, no signs of PHT and patent anastomoses. There were no retransplantations. Graft and patient survival at 1, 3, and 5 years were 83%, 75%, and 60%, respectively. Conclusions:Caval inflow to the graft is an efficacious salvage technique with satisfactory long-term results, considering the spontaneous outcome in patients denied LT because of diffuse PVT. Adequate preoperative management of PHT and its associated complications is vital in obtaining good results. In the long term, residual PHT resolves and the liver function returns to normal.

Liver transplantation for hepatocellular carcinoma: The impact of human immunodeficiency virus infection†

Liver transplantation (LT) has become an accepted therapy for end‐stage liver disease in human immunodeficiency virus–positive (HIV+) patients, but the specific results of LT for hepatocellular carcinoma (HCC) are unknown. Between 2003 and 2008, 21 HIV+ patients and 65 HIV− patients with HCC were listed for LT at a single institution. Patient characteristics and pathological features were analyzed. Univariate analysis for overall survival (OS) and recurrence‐free survival (RFS) after LT was applied to identify the impact of HIV infection. HIV+ patients were younger than HIV− patients [median age: 48 (range = 41‐63 years) versus 57 years (range = 37‐72 years), P < 0.001] and had a higher alpha‐fetoprotein (AFP) level [median AFP level: 16 (range = 3‐7154 μg/L] versus 13 μg/L (range = 1‐552 μg/L), P = 0.04]. There was a trend toward a higher dropout rate among HIV+ patients (5/21, 23%) versus HIV− patients (7/65, 10%, P = 0.08). Sixteen HIV+ patients and 58 HIV− patients underwent transplantation after median waiting times of 3.5 (range = 0.5‐26 months) and 2.0 months (range = 0.5‐24 months, P = 0.18), respectively. No significant difference was observed in the pathological features of HCC. With median follow‐up times of 27 (range = 5‐74 months) and 36 months (range = 3‐82 months, P = 0.40), OS after LT at 1 and 3 years reached 81% and 74% in HIV+ patients and 93% and 85% in HIV− patients, respectively (P = 0.08). RFS rates at 1 and 3 years were 69% and 69% in HIV+ patients and 89% and 84% in HIV− patients, respectively (P = 0.09). In univariate analysis, HIV status did not emerge as a prognostic factor for OS or RFS. Conclusion: Because of a higher dropout rate among HIV+ patients, HIV infection impaired the results of LT for HCC on an intent‐to‐treat basis but had no significant impact on OS and RFS after LT. (HEPATOLOGY 2011;53:475‐482)

Radiofrequency Ablation for Neuroendocrine Liver Metastases: A Systematic Review

To determine the efficacy of radiofrequency (RF) ablation in neuroendocrine tumor (NET) liver metastases. A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight studies were included (N = 301). Twenty-six percent of RF ablation procedures were percutaneous (n = 156), with the remainder conducted at surgery. Forty-eight percent of patients had a concomitant liver resection. Fifty-four percent of patients presented with symptoms, with 92% reporting symptom improvement following RF ablation (alone or in combination with surgery). The median duration of symptom improvement was 14-27 months. However, recurrence was common (63%-87%). RF ablation can provide symptomatic relief in NET liver metastases alone or in combination with surgery.

Neoadjuvant chemoradiotherapy followed by liver transplantation for unresectable cholangiocarcinoma: a single-centre national experience.

BACKGROUND Unresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA. MATERIALS AND METHODS Twenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients). RESULTS Twenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10-58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18-76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels. DISCUSSION In selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens.

Pancreatectomy for metastatic disease: a systematic review.

AIM Tumours rarely metastasise to the pancreas. While surgical resection of such metastases is believed to confer a survival benefit, there is limited data to support such management. We present a systematic review of case series of pancreatic metastasectomy and analysis of survival outcomes. METHODS A literature search was performed using the PubMed and Cochrane databases and the reference lists of relevant articles, searching for sizeable case series of pancreatic metastasectomy with curative intent. Data extracted included basic demographics, histological primary tumour, presentation, operative management, complications and survival, while the MINORS index was used to assess study quality. RESULTS 18 studies were found which met our inclusion criteria, involving 399 patients. Renal cell carcinoma (RCC) was the commonest malignancy metastasising to the pancreas, responsible for 62.6% of cases, followed by sarcoma (7.2%) and colorectal carcinoma (6.2%). While survival data was not uniformly reported, the median survival post-metastasectomy was 50.2 months, with a one-year survival of 86.81% and five-year survival of 50.02%. Median survival for RCC was 71.7 months with 70.4% five-year survival. Median survival was similar in patients with synchronous and metachronous pancreatic metastases, but patients with additional extrapancreatic metastases had a significantly shorter survival than patients with isolated pancreatic metastases (26 versus 45 months). Study quality was poor, with a median MINORS score of 10/16. CONCLUSIONS Within the limitations of a review of non-randomised case series, it would appear that pancreatic metastasectomy confers a survival benefit in selected patients. Better evidence is required, but may prove difficult to acquire.

Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia-reperfusion injury and clinical relevance

BACKGROUND Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). OBJECTIVE To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. PATIENTS AND METHODS Alternate patients were transplanted with right lobe grafts that were (n = 22; Group (Precond)) or were not (n = 22; Group (Control)) subjected to IPC in the living donor. Liver ischaemia-reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. RESULTS Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P = 0.8) and alanine aminotransferase (ALT) peaks (P = 0.6) were similar in both groups (307 +/- 189 and 437 +/- 302 vs. 290 +/- 146 and 496 +/- 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P = 0.003) and pre-operative bilirubin concentration (P = 0.004) were significantly predictive of minimum prothrombin time post-transplantation. CONCLUSIONS Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain.

Significance of isolated hepatic veno-occlusive disease/sinusoidal obstruction syndrome after liver transplantation.

After liver transplantation (LT), hepatic veno‐occlusive disease (VOD), which is also known as sinusoidal obstruction syndrome (SOS), has been reported initially in relation to azathioprine use and subsequently in relation to acute rejection (AR). Isolated veno‐occlusive disease (iVOD)/SOS raises some questions about its significance and especially its treatment. From the post‐LT biopsy samples of 1364 patients (2000‐2008), 31 patients with index biopsy samples showing VOD/SOS (2.3%) were identified. After a review of the index biopsy samples and previous biopsy samples, those patients not exposed to azathioprine therapy were subdivided into 2 groups according to the absence or presence of AR. Fifteen of the 31 patients had no previous evidence of AR, whereas 16 experienced episodes of AR (before or concurrently with VOD). The 2 groups were similar in terms of demographic and clinical data and the range of histological centrilobular changes. AR episodes were characterized by an endothelial predilection. iVOD/SOS occurred later than acute rejection–related veno‐occlusive disease (AR‐VOD)/SOS (mean times of 65 and 4.4 months, respectively, P = 0.0098). There was a tendency for iVOD/SOS to progress less frequently to chronic rejection in comparison with AR‐VOD/SOS (3/15 versus 9/15, P = 0.06). The histological resolution of iVOD/SOS was significantly more frequent in patients who benefited from increased immunosuppression in comparison with those who did not (5/7 versus 2/8, P = 0.05). When the groups were considered together, the same result was obtained (14/18 versus 4/12, P = 0.024). In conclusion, despite a constant overall prevalence of VOD/SOS, the proportion of iVOD/SOS has increased. The histological resolution of iVOD/SOS after increase in immunosuppression suggests an immune‐mediated origin. Better optimization of immunosuppression may be a curative treatment. Liver Transpl 17:798‐808, 2011.

Hepatic resection with in situ hypothermic perfusion is superior to other resection techniques.

Through the years, liver resection and bleeding control techniques have progressively evolved. However, for liver tumors located unfavorably, the standard techniques are not suitable due to either failure to control the bleeding or to liver ischemia induced by prolonged interruption of perfusion. In this regard, total vascular exclusion (TVE) with in situ hypothermic perfusion is advantageous as it protects the parenchyma, achieves better vascular control and enables difficult vascular reconstructions or reimplantations. The advantages of this procedure described as early as 1960s by Fortner were also confirmed by our team in a subsequent report. We showed that TVE with in situ hypothermic perfusion is superior to TVE alone if used for more than 60 min in complex resections with or without vascular reconstruction. Other techniques (ex situ liver resection developed by Pichlmayr and ante situm liver resection by Hannoun) have been described; however, they have not been widely accepted due to a high rate of complications. In this article, we report our operative technique as well as discuss some important operative points.