Emmanuel Melloul

Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations

BackgroundEnhanced Recovery After Surgery (ERAS) is a multimodal pathway developed to overcome the deleterious effect of perioperative stress after major surgery. In colorectal surgery, ERAS pathways reduced perioperative morbidity, hospital stay and costs. Similar concept should be applied for liver surgery. This study presents the specific ERAS Society recommendations for liver surgery based on the best available evidence and on expert consensus.MethodsA systematic review was performed on ERAS for liver surgery by searching EMBASE and Medline. Five independent reviewers selected relevant articles. Quality of randomized trials was assessed according to the Jadad score and CONSORT statement. The level of evidence for each item was determined using the GRADE system. The Delphi method was used to validate the final recommendations.ResultsA total of 157 full texts were screened. Thirty-seven articles were included in the systematic review, and 16 of the 23 standard ERAS items were studied specifically for liver surgery. Consensus was reached among experts after 3 rounds. Prophylactic nasogastric intubation and prophylactic abdominal drainage should be omitted. The use of postoperative oral laxatives and minimally invasive surgery results in a quicker bowel recovery and shorter hospital stay. Goal-directed fluid therapy with maintenance of a low intraoperative central venous pressure induces faster recovery. Early oral intake and mobilization are recommended. There is no evidence to prefer epidural to other types of analgesia.ConclusionsThe current ERAS recommendations were elaborated based on the best available evidence and endorsed by the Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.

ALPPS: from human to mice highlighting accelerated and novel mechanisms of liver regeneration.

Objectives:To develop a reproducible animal model mimicking a novel 2-staged hepatectomy (ALPPS: Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy) and explore the underlying mechanisms. Background:ALPPS combines portal vein ligation (PVL) with liver transection (step I), followed by resection of the deportalized liver (step II) within 2 weeks after the first surgery. This approach induces accelerated hypertrophy of the liver remnant to enable resection of massive tumor load. To explore the underlying mechanisms, we designed the first animal model of ALPPS in mice. Methods:The ALPPS group received 90% PVL combined with parenchyma transection. Controls underwent either transection or PVL alone. Regeneration was assessed by liver weight and proliferation-associated molecules. PVL-treated mice were subjected to splenic, renal, or pulmonary ablation instead of hepatic transection. Plasma from ALPPS-treated mice was injected into mice after PVL. Gene expression of auxiliary mitogens in mouse liver was compared to patients after ALPPS or PVL. Results:The hypertrophy of the remnant liver after ALPPS doubled relative to PVL, whereas mice with transection alone disclosed minimal signs of regeneration. Markers of hepatocyte proliferation were 10-fold higher after ALPPS, when compared with controls. Injury to other organs or ALPPS-plasma injection combined with PVL induced liver hypertrophy similar to ALPPS. Early initiators of regeneration were significantly upregulated in human and mice. Conclusions:ALPPS in mice induces an unprecedented degree of liver regeneration, comparable with humans. Circulating factors in combination with PVL seem to mediate enhanced liver regeneration, associated with ALPPS.

Low platelet counts after liver transplantation predict early posttransplant survival: The 60‐5 criterion

Platelets play a critical role in liver injury and regeneration. Thrombocytopenia is associated with increases in postoperative complications after partial hepatectomy, but it is unknown whether platelet counts could also predict outcomes after transplantation, a procedure that is often performed in thrombocytopenic patients. Therefore, the aim of this study was to evaluate whether platelet counts could be indicators of short‐ and long‐term outcomes after liver transplantation (LT). Two hundred fifty‐seven consecutive LT recipients (January 2003‐December 2011) from our prospective database were analyzed. Preoperative and daily postoperative platelet counts were recorded until postoperative day 7 (POD7). Univariate and multivariate analyses were performed to assess whether low perioperative platelet counts were a risk factor for postoperative complications and graft and patient survival. The median pretransplant platelet count was 88 × 109/L [interquartile range (IQR) = 58‐127 × 109/L]. The lowest platelet counts occurred on POD3: the median was 56 × 109/L (IQR = 41‐86 × 109/L). Patients with low platelet counts on POD5 had higher rates of severe (grade IIIb/IV) complications [39% versus 29%, odds ratio (OR) = 1.09 (95% CI = 1.1‐3.3), P = 0.02] and 90‐day mortality [16% versus 8%, OR = 2.25 (95% CI = 1.0‐5.0), P = 0.05]. In the multivariate analysis, POD5 platelet counts < 60 × 109/L were identified as an independent risk factor for grade IIIb/IV complications [OR = 1.96 (95% CI = 1.07‐3.56), P = 0.03)], graft survival [hazard ratio (HR) = 2.0 (95% CI = 1.1‐3.6), P = 0.03)], and patient survival [HR = 2.2 (95% CI = 1.1‐4.6), P = 0.03)]. The predictive value of platelet counts for graft and patient survival was lost in patients who survived 90 days. In conclusion, after LT, platelet counts < 60 × 109/L on POD5 (the 60‐5 criterion) are an independent factor associated with severe complications and early graft and patient survival. These findings may help us to develop protective strategies or specific interventions for high‐risk patients. Liver Transpl 20:147‐155, 2014.

Low Platelet Counts after Liver Transplantation Predict Early Post-Transplant Survival: The "60-5 Criterion"

Platelets play a critical role in liver injury and regeneration. Thrombocytopenia is associated with increases in postoperative complications after partial hepatectomy, but it is unknown whether platelet counts could also predict outcomes after transplantation, a procedure that is often performed in thrombocytopenic patients. Therefore, the aim of this study was to evaluate whether platelet counts could be indicators of short‐ and long‐term outcomes after liver transplantation (LT). Two hundred fifty‐seven consecutive LT recipients (January 2003‐December 2011) from our prospective database were analyzed. Preoperative and daily postoperative platelet counts were recorded until postoperative day 7 (POD7). Univariate and multivariate analyses were performed to assess whether low perioperative platelet counts were a risk factor for postoperative complications and graft and patient survival. The median pretransplant platelet count was 88 × 109/L [interquartile range (IQR) = 58‐127 × 109/L]. The lowest platelet counts occurred on POD3: the median was 56 × 109/L (IQR = 41‐86 × 109/L). Patients with low platelet counts on POD5 had higher rates of severe (grade IIIb/IV) complications [39% versus 29%, odds ratio (OR) = 1.09 (95% CI = 1.1‐3.3), P = 0.02] and 90‐day mortality [16% versus 8%, OR = 2.25 (95% CI = 1.0‐5.0), P = 0.05]. In the multivariate analysis, POD5 platelet counts < 60 × 109/L were identified as an independent risk factor for grade IIIb/IV complications [OR = 1.96 (95% CI = 1.07‐3.56), P = 0.03)], graft survival [hazard ratio (HR) = 2.0 (95% CI = 1.1‐3.6), P = 0.03)], and patient survival [HR = 2.2 (95% CI = 1.1‐4.6), P = 0.03)]. The predictive value of platelet counts for graft and patient survival was lost in patients who survived 90 days. In conclusion, after LT, platelet counts < 60 × 109/L on POD5 (the 60‐5 criterion) are an independent factor associated with severe complications and early graft and patient survival. These findings may help us to develop protective strategies or specific interventions for high‐risk patients. Liver Transpl 20:147‐155, 2014.

Developments in Liver Transplantation for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a serious health problem worldwide because of its association with hepatitis B and C viruses. In this setting, liver transplantation (LT) has become one of the best treatments since it removes both the tumor and the underlying liver disease. Due to the improvement of imaging techniques and surveillance programs, HCC are being detected earlier at a stage at which effective treatment is feasible. The prerequisite for long term success of LT for HCC depends on tumor load and strict selection criteria with regard to the size and number of tumor nodules. The need to obtain the optimal benefit from the limited number of organs available has prompted the maintenance of selection criteria in order to list only those patients with early HCC who have a better long-term outcome after LT. The indications for LT and organ allocation system led to many controversies around the use of LT in HCC patients. This review aims at giving the latest updated developments in LT for HCC focusing on selection criteria, diagnostic tools, prognostic factors, treatment on the waiting list, role of living donor liver transplantation and adjuvant therapy, and the impact of immunosuppression on HCC recurrence after LT.

Donor information for living donor liver transplantation: Where can comprehensive information be found?

Recently published data show that a large number of candidates for living donor liver transplantation (LDLT) actively look for additional information on the Internet because today it represents the main source of information for many of them. However, little is known about the quality of the information on LDLT available on the Internet. Our aim was, therefore, to comprehensively evaluate the online information available for LDLT candidates with the expanded Ensuring Quality Information for Patients (EQIP) tool (0‐36 items). One hundred Web sites on LDLT were initially found with the Google, Bing, and Yahoo search engines, and we identified 32 Web sites that provided specific information for such candidates in English. Only 9 Web sites addressed >20 items and the scores tended to be higher for educational (P = 0.13) and scientific sites (P = 0.07) compared to hospital sites. The median number of items from the EQIP tool was only 16 (interquartile range = 13‐20), and quantitative postoperative morbidity and mortality risk estimates were available on only 19% and 44% of the Web sites, respectively, despite the idea of major complications being mentioned on most Web sites. This analysis demonstrated several significant shortcomings in the quality of the information provided to potential donors for LDLT according to the EQIP instrument. We conclude that there is an urgent need to produce a Web site compliant with international standards for the quality of donor information. Liver Transpl, 2012.

Pulmonary embolism after elective liver resection: A prospective analysis of risk factors

BACKGROUND & AIMS Impairment of clotting factors after liver resection (LR) is considered to protect from the risk of pulmonary embolism (PE). We aimed at formally investigating the risk of PE after elective LR. METHODS From 2007 to 2009, 410 consecutive patients were prospectively analyzed to assess the risk of postoperative PE after LR with a thoracic CT scan, with or without a CT pulmonary angiography (CTPA). All patients were on a standardized thromboprophylaxis regimen. RESULTS PE was diagnosed in 24 (6%) patients within the first 10 postoperative days. Comparison between the PE group (n=24) and the non-PE group (n=386) showed a similar rate of metastatic liver disease (25 vs. 31%, p=0.308) but higher rates of BMI ≥ 25 kg/m(2) (75 vs. 46%, p=0.006), major LR (79 vs. 45%, p=0.003) and normal or minimally fibrotic liver parenchyma (92 vs. 73%, p=0.05). No patients with PE had inherited or acquired coagulation disorders. The 90-day mortality rate was similar in the two groups (4% vs. 3%, p=0.77), but the median hospital stay was longer in the PE group (20(IQR 16-27) vs. 11(IQR 8-16) days, p=0.001). On multivariate analysis, the independent predictors for PE were a BMI ≥ 25 kg/m(2) (adj. OR 5.27), major LR (adj. OR 3.13) and normal or minimally fibrotic liver parenchyma (adj. OR 4.21). CONCLUSIONS In addition to patient characteristics (high BMI), major resection and normal liver parenchyma increase the risk of PE after LR. This suggests that specific thromboembolic mechanisms are involved in liver regeneration and advocates more aggressive thromboprophylaxis in the high-risk groups.

Management of severe blunt hepatic injury in the era of computed tomography and transarterial embolization: A systematic review and critical appraisal of the literature.

BACKGROUND During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. METHOD The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence “Quality Assessment for Case Series” system. RESULTS Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2–6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6–75). A median of 66% (range, 0–100%) of patients was managed with NOM, with a success rate of 94% (range, 86–100%). TAE was used in only 3% of cases (range, 0–72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81–100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17–100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0–8%) after NOM and 51% (range, 30–68%) after surgery. CONCLUSION NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. LEVEL OF EVIDENCE Systematic review, level IV

Extended Lymphadenectomy in Patients With Pancreatic Cancer Is Debatable

Lymph node staging is one of the most important factors in determining the prognosis after resection of pancreatic ductal adenocarcinoma. Despite ongoing efforts to further refine lymph node staging, the debate on the extent of lymphadenectomy during pancreaticoduodenectomy is still open. The purpose of this review was to summarize the evidence about performing standard lymphadenectomy during curative resection of pancreatic cancer. All four prospective randomized controlled trials published concluded that extended lymphadenectomy does not contribute to better oncologic outcome for patients with adenocarcinoma of the pancreatic head. Indeed, one major drawback of extended lymphadenectomy is the higher risk of persistent postoperative diarrhea. No prospective randomized studies could be found on the role of extended lymphadenectomy in patients with adenocarcinoma of the corpus and tail. Based on current evidence there is no indication that extended lymphadenectomy should be performed routinely during resection of pancreatic cancer.

Cystic lymphangioma of the adrenal gland: report of a case and review of the literature

BackgroundCystic lymphangioma is a rare tumor of the lymphatic vessels that occurs more frequently in women. Location of this pathology can be diverse but most commonly occurs in the neck or axilla. Cystic lymphangioma originating from the adrenal tissue represents a very rare entity.Case presentationWe report here the case of a 38-year-old woman who was diagnosed with a cystic retroperitoneal mass. After further investigations, the patient was suspected to have a left adrenal cystic lymphangioma. She underwent successful open left adrenalectomy as curative treatment, and the diagnosis of cystic lymphangioma of the left adrenal gland was confirmed at histology. The postoperative course was uneventful.ConclusionThis case report and review of the literature bring new insights into the diagnostic difficulty and management of cystic lymphangioma of the adrenal gland.