Dimitri Aristotle Raptis

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.

A multicenter randomized clinical trial of primary anastomosis or Hartmann's procedure for perforated left colonic diverticulitis with purulent or fecal peritonitis.

Objectives:To evaluate the outcome after Hartmanns procedure (HP) versus primary anastomosis (PA) with diverting ileostomy for perforated left-sided diverticulitis. Background:The surgical management of left-sided colonic perforation with purulent or fecal peritonitis remains controversial. PA with ileostomy seems to be superior to HP; however, results in the literature are affected by a significant selection bias. No randomized clinical trial has yet compared the 2 procedures. Methods:Sixty-two patients with acute left-sided colonic perforation (Hinchey III and IV) from 4 centers were randomized to HP (n = 30) and to PA (with diverting ileostomy, n = 32), with a planned stoma reversal operation after 3 months in both groups. Data were analyzed on an intention-to-treat basis. The primary end point was the overall complication rate. The study was discontinued following an interim analysis that found significant differences of relevant secondary end points as well as a decreasing accrual rate (NCT01233713). Results:Patient demographics were equally distributed in both groups (Hinchey III: 76% vs 75% and Hinchey IV: 24% vs 25%, for HP vs PA, respectively). The overall complication rate for both resection and stoma reversal operations was comparable (80% vs 84%, P = 0.813). Although the outcome after the initial colon resection did not show any significant differences (mortality 13% vs 9% and morbidity 67% vs 75% in HP vs PA), the stoma reversal rate after PA with diverting ileostomy was higher (90% vs 57%, P = 0.005) and serious complications (Grades IIIb-IV: 0% vs 20%, P = 0.046), operating time (73 minutes vs 183 minutes, P < 0.001), hospital stay (6 days vs 9 days, P = 0.016), and lower in-hospital costs (US

The model for end-stage liver disease allocation system for liver transplantation saves lives, but increases morbidity and cost: a prospective outcome analysis

16,717 vs US

Novel and simple preoperative score predicting complications after liver resection in noncirrhotic patients.

24,014) were significantly reduced in the PA group. Conclusions:This is the first randomized clinical trial favoring PA with diverting ileostomy over HP in patients with perforated diverticulitis.

What is critical for liver surgery and partial liver transplantation: size or quality?

We analyzed the first 100 patients who underwent liver transplantation by Model for End‐Stage Liver Disease (MELD) allocation, and compared the outcome of patients on the waiting list and after orthotopic liver transplantation with the last 100 patients who underwent transplantation prior to the introduction of the MELD system in July 2007. MELD allocation resulted in decreased waiting list mortality (386 versus 242 deaths per 1000 patient‐years, P < 0.0001) and the transplantation of sicker recipients (uncorrected median MELD score 13.5 versus 20, P = 0.003). Recipient posttransplant morbidity was significantly higher, mainly caused by increased percentage of renal failure requiring renal replacement therapy (13 versus 46%, P < 0.0001). However, kidney function recovered in most cases within 6 months after OLT. Hospital mortality remained similar in both groups (6% versus 9%). Patient 1‐year survival was 91% versus 83% (pre‐MELD versus MELD era, P = 0.2154), graft 1‐year survival was 88% versus 78% (P = 0.1013), respectively. Costs accumulated were significantly higher after introduction of the MELD policy (US

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

81,967 versus US

Liver Failure After Extended Hepatectomy in Mice Is Mediated by a p21-Dependent Barrier to Liver Regeneration

127,453, a 55% increase, P = 0.02) with a strong correlation with the individual MELD score (P < 0.0001). The MELD system addresses the goal of fairness well. However, the postoperative course appears more difficult in the MELD era with increased financial burden, but reasonable patient and graft survival. This is the inevitable price to balance justice and utility in liver graft allocation. Liver Transpl 17:674–684, 2011.

MRI: the new reference standard in quantifying hepatic steatosis?

Objective:To develop and validate a simple score to predict postoperative complications by severity after liver resection, using readily available preoperative risk factors. Background:Although liver surgery has enjoyed major development with dramatic reduction in mortality rates, the incidence of serious yet nonlethal complications remains high. No scoring system is currently available to identify those patients at higher risk for a complicated course. Methods:Complications were prospectively assessed in 615 consecutive noncirrhotic patients undergoing liver resection at the same institution. In randomly selected 60% of the population, multivariate-logistic-regression analysis was used to develop a score to predict severe complications defined as complications grades III, IV, and mortality (grade V) (Clavien-Dindo classification). The score was validated by calibration within the remaining 40% of the patients. Results:Grades III to V complications occurred in 159 (26%) of the 615 patients after liver resection, 90 (15%) were grade III, 48 (8%) grade IV, and 21 (3%) grade V. Four preoperative parameters were identified as independent predictors including American Society of Anesthesiologists category, transaminases levels (aspartate aminotransferase), extent of liver resection (>3 vs <3 segments), and the need for an additional hepaticojejunostomy or colon resection. A prediction score was calculated on the basis of 60% of the population (369 patients) using the 4 independent predictors ranging from 0 to 10 points. The risk to develop serious postoperative complications was 16% in “low risk” patients (0–2 points), 37% in “intermediate risk” patients (3–5 points) and 60% in “high risk” patients (6–10 points). The predicted mean for absolute risk for grades III to V complications was 27% in the validation population including 40% of the patients (n = 246), whereas the observed risk was 24%. Predicted and observed risks were similar throughout the different risk categories (P = 0.8). The score was significantly associated with hospital and intensive care unit stays. Costs of the entire procedure doubled among the 3 risk groups. Conclusions:This novel and simple score accurately predicts postoperative complications and cost in patients undergoing liver resection. This score allows early identification of patients at risk and may impact not only decision making for surgical intervention but also quality assessment and reimbursement.

Quantification of liver fat in the presence of iron and iodine: an ex-vivo dual-energy CT study.

M ajor liver resections and partial orthotopic liver transplantation (OLT) have become established procedures in liver surgery; for many patients, these techniques offer the only curative option. Yet, many patients develop postoperative complications because the remnant livers or grafts are too small or of poor quality to sustain sufficient organ function. This somewhat new and poorly defined phenomenon has been termed ‘‘small-for-size syndrome’’ (SFSS) to describe this scenario. The concept is, in fact, not a new one, because as early as the 1970s, Thomas E. Starzl described the complicated postoperative course of a young woman subjected to an almost 90% hepatectomy and who was subsequently characterized by prolonged hyperbilirubinemia, encephalopathy, and coagulopathy. In an unconventional way for a review, we will start with three case reports to illustrate the scope and clinical relevance of SFSS after liver surgery and transplantation. Case 1: A 47-year-old healthy man, whose wife was listed for OLT due to a symptomatic nonresectable hemangioendothelioma of the liver, offered to be considered for living donor liver transplantation (LDLT). Following the standard work-up for this procedure, he underwent a right hemi-hepatectomy including the middle hepatic vein to serve as allograft for his wife. The remnant left hemi-liver was estimated by computed tomographic (CT) volumetry to weigh 450 g, i.e., around 32% of the whole liver. The ratio of the remnant liver weight to body weight (RLBW) was 0.65%. The donor had a difficult postoperative course developing mild encephalopathy and hyperbilirubinemia lasting 20 days peaking at 178 lmol/L (10.4 mg/ dL) by day five, and severe coagulopathy (prothrombin time <30%) that normalized by day 7. The donor eventually recovered fully, and was discharged in good general condition 22 days after surgery. Case 2: A 42-year-old male was listed for OLT because of Child B cirrhosis (Model for End-Stage Liver Disease [MELD] score: 21) and a small (3 cm) hepatocellular carcinoma (HCC) related to hepatitis B virus infection. He received the right hemi-liver containing the middle hepatic vein from his wife (graft weighing 620 g), who had an uneventful postoperative course. The ratio of graft size in grams to her husband’s body weight (80 kg) (graft-to-recipient weight ratio [GRWR]) was 0.7%. The postoperative period was complicated by encephalopathy, hyperbilirubinemia (up to 262 lmol/L, 15.3 mg/dL) for 2 weeks, and prolonged coagulopathy with a factor V level below 20% at day 4. As a result of the delayed graft function, the patient required intensive care unit treatment for 1 week before the liver graft function improved. He was able to be discharged in good general condition on postoperative day 21. Case 3: A 58-year-old male presented with multiple colorectal liver metastases in the right hemi-liver as well as in segment II, III, and 10 months after resection of the primary rectal tumor followed by 5 cycles of chemotherapy containing Folfox and Avastin. A Abbreviations: CALI, chemotherapy-associated liver injury; CT, computed tomography; DOI, 2,5-dimethoxy-4-iodoamphetamine; EHPBA, European Hepato-Pancreatico-Biliary Association; GRWR, graft-to-recipient weight ratio; HCC, hepatocellular carcinoma; IHPBA, International Hepato-PancreaticoBiliary Association; IL-6, interleukin-6; LDLT, living donor liver transplantation; MELD, Model for End-Stage Liver Disease; OLT, orthotopic liver transplantation; PTX, pentoxifylline; RLBW, remnant liver to body weight; SFSS, small-for-size syndrome; TNF, tumor necrosis factor. From the Swiss Hepato-Pancreatico-Biliary and Transplantation Center, Department of Surgery, University of Zurich, Zurich, Switzerland Funded in part by Grants from the Swiss National Foundation to P.A.C. (SNF 3200B0-109906), Krebsliga Zurich, Switzerland and Sassella Stiftung Zurich, Switzerland, also to P.A.C. Presented as a Thomas E. Starzl Transplant Surgery State-of-the-Art Lecture at the 60th Annual Meeting of the American Association for the Study of Liver Diseases; October 30-November 3, 2009; Boston, MA. This article is dedicated to Thomas E. Starzl for his lifelong contribution to liver surgery and transplantation. Address reprint requests to: Pierre-Alain Clavien, M.D., Ph.D., Department of Surgery, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. E-mail: clavien@access.uzh.ch; fax: þ41 44 255 44 49. CopyrightVC 2010 by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hep.23713 Potential conflict of interest: Nothing to report.

Laparoscopic versus open pancreas resection for pancreatic neuroendocrine tumours: a systematic review and meta-analysis

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.