Henrik Petrowsky

Evidence-based Value of Prophylactic Drainage in Gastrointestinal Surgery: A Systematic Review and Meta-analyses

Objective:To determine the evidence-based value of prophylactic drainage in gastrointestinal (GI) surgery. Methods:An electronic search of the Medline database from 1966 to 2004 was performed to identify articles comparing prophylactic drainage with no drainage in GI surgery. The studies were reviewed and classified according to their quality of evidence using the grading system proposed by the Oxford Centre for Evidence-based Medicine. Seventeen randomized controlled trials (RCTs) were found for hepato-pancreatico-biliary surgery, none for upper GI tract, and 13 for lower GI tract surgery. If sufficient RCTs were identified, we performed a meta-analysis to characterize the drain effect using the random-effects model. Results:There is evidence of level 1a that drains do not reduce complications after hepatic, colonic, or rectal resection with primary anastomosis and appendectomy for any stage of appendicitis. Drains were even harmful after hepatic resection in chronic liver disease and appendectomy. In the absence of RCTs, there is a consensus (evidence level 5) about the necessity of prophylactic drainage after esophageal resection and total gastrectomy due to the potential fatal outcome in case of anastomotic and gastric leakage. Conclusion:Many GI operations can be performed safely without prophylactic drainage. Drains should be omitted after hepatic, colonic, or rectal resection with primary anastomosis and appendectomy for any stage of appendicitis (recommendation grade A), whereas prophylactic drainage remains indicated after esophageal resection and total gastrectomy (recommendation grade D). For many other GI procedures, especially involving the upper GI tract, there is a further demand for well-designed RCTs to clarify the value of prophylactic drainage.

How Should Transection of the Liver Be Performed?: A Prospective Randomized Study in 100 Consecutive Patients: Comparing Four Different Transection Strategies

Objective:To identify the most efficient parenchyma transection technique for liver resection using a prospective randomized protocol. Summary Background Data:Liver resection can be performed by different transection devices with or without inflow occlusion (Pringle maneuver). Only limited data are currently available on the best transection technique. Methods:A randomized controlled trial was performed in noncirrhotic and noncholestatic patients undergoing liver resection comparing the clamp crushing technique with Pringle maneuver versus CUSA versus Hydrojet versus dissecting sealer without Pringle maneuver (25 patients each group). Primary endpoints were intraoperative blood loss, resection time, and postoperative liver injury. Secondary end points included the use of inflow occlusion, postoperative complications, and costs. Results:The clamp crushing technique had the highest transection velocity (3.9 ± 0.3 cm2/min) and lowest blood loss (1.5 ± 0.3 mL/cm2) compared with CUSA (2.3 ± 0.2 cm2/min and 4 ± 0.7 mL/cm2), Hydrojet (2.4 ± 0.3 cm2/min and 3.5 ± 0.5 mL/cm2), and dissecting sealer (2.5 ± 0.3 cm2/min and 3.4 ± 0.4 mL/cm2) (velocity: P = 0.001; blood loss: P = 0.003). Clamp crushing technique was associated with the lowest need for postoperative blood transfusions. The degree of postoperative reperfusion injury and complications were not significantly different among the groups. The clamp crushing technique proved to be most cost-efficient device and had a cost-saving potential of 600 &U20AC; to 2400 &U20AC; per case. Conclusions:The clamp crushing technique was the most efficient device in terms of resection time, blood loss, and blood transfusion frequency compared with CUSA, Hydrojet, and dissecting sealer, and proved to be also the most cost-efficient device.

Ischaemia–reperfusion injury in liver transplantation—from bench to bedside

Ischaemia–reperfusion injury (IRI) in the liver, a major complication of haemorrhagic shock, resection and transplantation, is a dynamic process that involves the two interrelated phases of local ischaemic insult and inflammation-mediated reperfusion injury. This Review highlights the latest mechanistic insights into innate–adaptive immune crosstalk and cell activation cascades that lead to inflammation-mediated injury in livers stressed by ischaemia–reperfusion, discusses progress in large animal experiments and examines efforts to minimize liver IRI in patients who have received a liver transplant. The interlinked signalling pathways in multiple hepatic cell types, the IRI kinetics and positive versus negative regulatory loops at the innate–adaptive immune interface are discussed. The current gaps in our knowledge and the pathophysiology aspects of IRI in which basic and translational research is still required are stressed. An improved appreciation of cellular immune events that trigger and sustain local inflammatory responses, which are ultimately responsible for organ injury, is fundamental to developing innovative strategies for treating patients who have received a liver transplant and developed ischaemia–reperfusion inflammation and organ dysfunction.

Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case-control study.

Objective:To assess the impact of microsteatosis (MiS) and macrosteatosis (MaS) on major hepatectomy. Summary Background Data:While steatosis of a liver graft is an established risk factor in transplantation, its impact on major hepatectomy remains unclear. Methods:Fifty-eight steatotic patients who underwent major hepatectomy were matched 1:1 with patients with normal liver according to age, gender, ASA score, diagnosis, extent of hepatectomy, and need of hepaticojejunostomy. Steatosis was evaluated quantitatively and qualitatively. Primary endpoints were mortality and complications. Results:Pure MaS and MiS were present in only 10 and 3 patients, respectively, while mixed steatosis was noted in 45 patients. Forty-four patients had mild (10%–30%) and 14 moderate/severe (>30%) steatosis. Steatotic patients had significantly higher serum transaminase and bilirubin levels, and lower prothrombin time. Blood loss (P = 0.04) and transfusions (P = 0.03), and ICU stay (P = 0.001) were increased in steatotic patients. Complications were higher in steatotic patients when considered either overall (50% vs. 25%, P = 0.007) or major (27.5% vs. 6.9%, P = 0.001) complications. Patients with pure MaS had increased mortality (MaS: 20% vs. MiS: 6.6% vs. mixed: 0%; P = 0.36) and major complications (MaS: 66% vs. MiS: 50% vs. mixed: 24%; P = 0.59), but not significantly. Preoperative cholestasis was a highly significant risk factor for mortality in patients with hepatic steatosis. Conclusion:Steatosis per se is a risk factor for postoperative complications after major hepatectomy and should be considered in the planning of surgery. Caution must be taken to perform major hepatectomy in steatotic patients with preexisting cholestasis.

A Prospective, Randomized, Controlled Trial Comparing Intermittent Portal Triad Clamping Versus Ischemic Preconditioning With Continuous Clamping for Major Liver Resection

Objective:To evaluate whether ischemic preconditioning (IP) with continuous clamping or intermittent clamping (IC) of the portal triad confers better protection during liver surgery. Summary Background Data:IP and IC are distinct protective approaches against ischemic injury. Since both strategies proved to be superior in randomized controlled trials (RCTs) to continuous inflow occlusion alone, we designed a RCT to compare IP and IC in patients undergoing major liver resection. Methods:Noncirrhotic patients undergoing major liver resection were randomized to receive IP with inflow occlusion (n = 36) or IC (n = 37). Primary endpoints were postoperative liver injury and intraoperative blood loss. Postoperative liver injury was assessed by peak values of AST (alanine aminotransferase) and ALT (aspartate aminotransferase), as well as the area under the curve (AUC) of the postoperative transaminase course. Secondary endpoints included resection time, the need of blood transfusion, ICU, and hospital stay as well as postoperative complications and mortality. Results:Both groups were comparable regarding demographics, ASA score, type of hepatectomy, duration of inflow occlusion (range, 30–75 minutes), and resection surface. The transection-related blood loss was 146 versus 250 mL (P = 0.008), and when standardized to the resection surface 1.2 versus 1.8 mL/cm2 (P = 0.01) for IP and IC, respectively. Although peak AST, AUCAST, and AUCALT were lower for IC, the differences did not reach statistical significance. Overall (42% vs. 38%) and major (33 vs. 27%) postoperative complications as well as median ICU (1 vs. 1 day) and hospital stay (10 vs. 11 days) were similar between both groups. Conclusions:Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection. However, IP is associated with lower blood loss and shorter transection time. Therefore, both strategies can be recommended for noncirrhotic patients undergoing liver resection.

Early survival and safety of ALPPS: first report of the International ALPPS Registry.

Objectives:To assess safety and outcomes of the novel 2-stage hepatectomy, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), using an international registry. Background:ALPPS induces accelerated growth of small future liver remnants (FLR) to allow curative resection of liver tumors. There is concern about safety based on reports of higher morbidity and mortality. Methods:A Web-based data entry system was created with password access and data pseudoencryption (NCT01924741). All patients with complete 90-day data were included. Multivariate logistic regression analysis was performed to identify independent risk factors for severe complications and mortality and volume growth of the FLR. Results:Complete data were available for 202 patients. A total of 141 (70%) patients had colorectal liver metastases (CRLM). Median starting standardized future liver remnants of 21% increased by 80% within a median of 7 days. Ninety-day mortality was 19/202 (9%). Severe complications including mortalities (Clavien-Dindo ≥IIIb) occurred in 27% of patients. Independent factors for severe complications were red blood cell transfusion [odds ratio (OR), 5.2), ALPPS stage I operating time greater than 300 minutes (OR, 4.4), age more than 60 years (OR, 3.8), and non-CRLM (OR, 2.7). Age, use of Pringle maneuver, and histologic changes led to less volume growth. In patients younger than 60 years with CRLM, 90-day mortality was similar to conventional 2-stage hepatectomies for CRLM. Conclusions:This is the first analysis of the ALPPS registry showing that ALPPS has increased perioperative morbidity and mortality in older patients but better outcomes in patients with CRLM.

Use of severely steatotic grafts in liver transplantation: a matched case-control study.

Background:Although there is a worldwide need to expand the pool of available liver grafts, cadaveric livers with severe steatosis (>60%) are discarded for orthotopic liver transplantation (OLT) by most centers. Methods:We analyzed patients receiving liver grafts with severe steatosis between January 2002 and September 2006. These patients were matched 1:2 with control patients without severe steatosis according to status the waiting list, recipient age, recipient body mass index (BMI), and model for end-stage liver disease (MELD) score. Primary end points were the incidence of primary graft nonfunction (PNF), and graft and patient survival. Secondary end points included primary graft dysfunction (PDF), the incidence of postoperative complications, and histologic assessment of steatosis in follow-up biopsies. We also conducted a survey on the use of grafts with severe steatosis among leading European liver transplant centers. Results:During the study period, 62 patients dropped out of the waiting list and 45 of them died due to progression of disease. Of 118 patients who received transplants 20 (17%) received a graft with severe steatosis during this period. The median degree of total liver steatosis was 90% (R = 65%–100%) for the steatotic group. The steatotic (n = 20) and matched control group (n = 40) were comparable in terms of recipient age, BMI, MELD score, and cold ischemia time. The steatotic group had a significantly higher rate of PDF and/or renal failure. Although the median intensive care unit (ICU) and hospital stay were not significantly different between both groups, the proportion of patients with long-term ICU (≥21 days) and hospital (≥40 days) stay was significantly higher for patients with a severely steatotic graft. Sixty-day mortality (5% vs. 5%) and 3-year patient survival rate (83% vs. 84%) were comparable between the control and severe steatosis group. Postoperative histologic assessment demonstrated that the median total amount of liver steatosis decreased significantly (median: 90% to 15%, P < 0.001). Our survey showed that all but one of the European centers currently reject liver grafts with severe steatosis for any recipient. Conclusion:Due to the urgent need of liver grafts, severely steatotic grafts should be no longer discarded for OLT. Maximal effort must be spent when dealing with these high-risk organs but the use of severely steatotic grafts may save the lives of many patients who would die on the waiting list.

Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis.

A combined antiviral and tumoricidal effect of interferon (IFN) is assumed to occur after resection or ablation of hepatocellular carcinoma (HCC).

Comparative Analysis of Resection and Liver Transplantation for Intrahepatic and Hilar Cholangiocarcinoma: A 24-Year Experience in a Single Center

OBJECTIVES To compare the survival difference between 2 surgical modalities in the treatment of locally advanced intrahepatic and hilar cholangiocarcinoma (CCA) and to identify factors that predict mortality. DESIGN Retrospective study. SETTING University transplant center. PATIENTS Of the 132 patients with a diagnosis of CCA treated from February 1, 1985, through June 30, 2009, 75 had metastatic disease at presentation and were excluded from the study, whereas 57 patients were candidates for surgical therapy. Tumor type was intrahepatic in 37 patients and hilar in 20 patients. Surgical therapy included orthotopic liver transplant (OLT) in 38 patients and combined radical bile duct resection with partial hepatectomy (RR) in 19 patients. RESULTS Tumors were locally advanced in 35 of 37 patients (95%) with intrahepatic tumors and 16 of 20 patients (80%) with hilar tumors. Adjunctive therapy was used in 35 patients (61%). The 5-year tumor recurrence-free patient survival was significantly higher in the OLT group compared with the RR group (33% vs 0%; P = .05). In the OLT group, neoadjuvant and adjuvant therapies resulted in better patient survival compared with no therapy or adjuvant therapy only (47% vs 20% vs 33%, respectively; P = .03). Multivariate factors predictive of worse survival outcomes included hilar CCA, multifocal tumors, perineural invasion, and RR as the treatment modality compared with OLT. Tumor sizes--5 cm or larger for intrahepatic and 3 cm or larger for hilar CCA--were not predictors of poor outcome. CONCLUSION Orthotopic liver transplant in combination with neoadjuvant and adjuvant therapies is superior to RR with adjuvant therapy in locally advanced intrahepatic and hilar CCA.

Prediction of Mortality After ALPPS Stage-1: An Analysis of 320 Patients From the International ALPPS Registry.

OBJECTIVES The aim of this study was to identify predictors of 90-day mortality after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), available after stage-1, either to omit or delay stage-2. BACKGROUND DATA ALPPS is a two-stage hepatectomy for patients with extensive liver tumors with predicted small liver remnants, which has been criticized for its high mortality rate. Risk factors for mortality are unknown. METHODS Patients in the International Registry undergoing ALPPS from April 2011 to July 2014 were analyzed. Primary outcome was 90-day mortality. Liver function after stage-1 was assessed using the criteria of the International Study Group for Liver Surgery (ISGLS) after stage-1 among others. A multivariable model was used to identify independent predictors of 90-day mortality. RESULTS Three hundred twenty patients registered by 55 centers worldwide were evaluated. Overall 90-day mortality was 8.8% (28/320). The predominant cause for 90-day mortality was postoperative liver failure in 75% of patients. Fourteen percent of patients developed liver failure according to ISGLS criteria already after stage-1 ALPPS. Those and patients with a model of end-stage liver disease (MELD) score more than 10 before stage-2 were at significantly higher risk for 90-day mortality after stage-2 with an odds ratio (OR) 3.9 [confidence interval (CI) 1.4-10.9, P = 0.01] and OR 4.9 (CI 1.9-12.7, P = 0.006), respectively. Other factors, such as size of future liver remnant (FLR) before stage-2 and time between stages, were not predictive. CONCLUSIONS This analysis of the largest cohort of ALPPS patients so far identifies those patients in whom stage-2 ALPPS surgery should be delayed or even denied. These findings may help to make ALPPS safer.