José Manuel Asencio

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial ovarian carcinoma: upfront therapy, at first recurrence, or later?

AIM Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) has been proposed as treatment for advanced epithelial ovarian carcinoma (EOC). No consensus exists on when to administer CRS+HIPEC during the natural history of the disease, namely, as upfront therapy, at first recurrence, or at second or subsequent recurrence. PATIENTS AND METHODS We analyzed a series of patients with advanced EOC collected prospectively in an institution with a peritoneal malignant disease treatment program. Patients were treated with CRS+HIPEC upfront, at first recurrence, and at second or subsequent recurrence. RESULTS We treated 42 patients: 15 upfront, 19 at first recurrence, and 8 at second or subsequent recurrence. Cytoreduction was complete (CC0) in 75% of cases; residual disease was <2.5 mm (CC1) in 25%. Severe morbidity (CTCAE v.3.0, grade 3-4) was 26%, and hospital mortality was 7%. After a median follow-up of 24 months, median overall survival was 77.8 months for patients treated upfront, 62.8 months for patients treated at first recurrence, and 35.7 months for patients treated at second or subsequent recurrence. Disease-free survival was 21.1 months, 18 months, and 5.7 months, respectively. Overall survival in the upfront and first recurrence groups was similar, and statistically significant differences with the second recurrence group were identified (p<0.03). CONCLUSIONS Treatment of advanced EOC using CRS+HIPEC is promising in terms of overall survival and disease-free survival when administered as upfront and at first recurrence therapy. These results warrant further evaluation in a randomized trial.

How to expand the safe limits in hepatic resections

The size of the remnant liver after an extended hepatectomy is currently the main limiting factor for performing curative hepatic surgery in patients with tumors and liver metastasis. The current guidelines for extended hepatectomies require that the future remnant liver volume needs to be higher than 20% of the original liver in healthy organs, of 30% in livers with steatosis or exposed to chemotherapy, and of 40% in patients with cirrhosis in order to prevent the “small‐for‐size” syndrome, characterized by the development of liver dysfunction with ascites, coagulopathy and cholestasis. Observations from the use of small liver grafts in liver transplantation and an increased surgical experience has improved our understanding of the mechanisms responsible for the development of liver dysfunction after extended hepatectomies. Increasing the size of the future liver remnant, the introduction of the “small‐for‐flow” concept with the perioperative monitoring and modulation of portal blood flow and pressure, and the exploration of the potential effects of regeneration preconditioning, are all promising strategies that could expand the indications and increase the safety of liver surgery.

Early Measurement of Indocyanine Green Clearance Accurately Predicts Short-Term Outcomes After Liver Transplantation.

Background There are no accurate tools to predict short-term mortality or the need for early retransplantation after liver transplantation (LT). A noninvasive measurement of indocyanine green clearance, the plasma disappearance rate (PDR), has been associated with initial graft function. Methods We evaluated the ability of PDR to predict early mortality or retransplantation after LT. In this observational prospective study, 332 LT were analyzed. Donor, recipient, and intraoperative data were investigated. The ensuing score was prospectively evaluated in a validation cohort of 77 patients. Results Thirty-three patients reached the main endpoint. By multivariate analysis, the only independent predictors of the endpoint were PDR (odds ratio [OR], 0.85; 95% confidence interval, 0.79-0.92) and international normalized ratio (OR, 1.45; 95% confidence interval, 1.17-1.82). A risk score weighted by the OR was built using cutoff values of 2.2 or greater for international normalized ratio (1 point) and less than 10%/min for PDR (2 points). Four categories (0 to 3) were possible. The risk of early death or retransplantation was associated with the score (0, 4.4%; 1, 6.5%; 2, 12%; and 3, 50%; &khgr;2 for trend, P < 0.001). The score was also associated with duration of mechanical ventilation and intensive care unit stay. The score had a good diagnostic performance in the validation cohort (sensitivity, 60%; specificity, 95.5%; positive predictive value, 66.7%; negative predictive value, 94.1%). Conclusions A simple score obtained within the first day after LT predicts short-term survival and need for retransplantation and may prove useful when selecting diagnostic and therapeutic strategies.

Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy

Background: Portal vein embolization is performed weeks before extended hepatic resections to increase the future liver remnant and prevent posthepatectomy liver failure. Portal vein embolization performed closer to the operation also could be protective, but worsening of portal hyper‐perfusion is a major concern. We determined the hepatic hemodynamic effects of a portal vein embolization performed 24 hours prior to hepatic operation. Methods: An extended (90%) hepatectomy was performed in swine undergoing (portal vein embolization) or not undergoing (control) a portal vein embolization 24 hours earlier (n = 10/group). Blood tests, hepatic and systemic hemodynamics, hepatic function (plasma disappearance rate of indocyanine green), liver histology, and volumetry (computed tomographic scanning) were assessed before and after the hepatectomy. Hepatocyte proliferating cell nuclear antigen expression and hepatic gene expression also were evaluated. Results: Swine in the control and portal vein embolization groups maintained stable systemic hemodynamics and developed similar increases of portal blood flow (302 ± 72% vs 486 ± 92%, P = .13). Portal pressure drastically increased in Controls (from 9.4 ± 1.3 mm Hg to 20.9 ± 1.4 mm Hg, P < .001), while being markedly attenuated in the portal vein embolization group (from 11.4 ± 1.5 mm Hg to 16.1 ± 1.3 mm Hg, P = .061). The procedure also improved the preservation of the hepatic artery blood flow, liver function, and periportal edema. These effects occurred in the absence of hepatocyte proliferation or hepatic growth and were associated with the induction of the vasoprotective gene Klf2. Conclusion: Portal vein embolization preconditioning represents a potential hepato‐protective strategy for extended hepatic resections. Further preclinical studies should assess its medium‐term effects, including survival. Our study also supports the relevance of hepatic hemodynamics as the main pathogenetic factor of post‐hepatectomy liver failure.

Donor Risk Index could be a Predictor of “Resistant to Flow” Liver Grafts

Introduction The Donor Risk Index (DRI) was validated with the aim of being a predictive model of graft survival based on donor characteristics. The measurement of intraoperative arterial hepatic flow and clearance of indocyanine green (PDR-ICG) are variables in the intraoperative time that reflects graft perfusion and they could be influenced by the quality of the grafts. Aim To analyze the influence of DRI on intraoperative liver hemodynamic alterations and on intraoperative dynamic liver function tests (PDR-ICG). Materials and Methods We propose an observational study of a single center cohort (n = 228). The measurement of the intraoperative flows is made with a flow meter VeriQ). ICG-PDR was obtained from all patients with a LiMON monitor (Pulsion Medical Systems AG, Munich, Germany). DRI was calculated by the previously validated formula. Unless otherwise stated, data were expressed as mean (SD, standard deviation) or n (%). When data were normally distributed (based on the Kolmogorov-Smirnov test) they were compared using the t-Student test. The qualitative variables and risk measurement was analyzed using the chi-square test. Kaplan Meir curves were used to show survival analysis. Results DRI mean value ??was 1.58 ± 0.31. DRI> 1.7 group was considered grafts of poor quality had an intraoperative arterial flow 234.2 ± 121.35 ml / min compared with DRI <1.70 group with an intraoperative arterial flow of 287, 24 ± 156.84, p = 0.02. DRI > 1,7 grafts showed a increase risk to test a low arterial flow less than 180 ml/min. (OR: 1,89 95% confidence interval [95% CI], 1,35-3,35).p<0.04). DRI> 1.70 group had a 60min ICG-PDR of 14.75 ± 6.52% / min compared with DRI <1.70 group with a 60min ICG-PDR of 16.68 ± 6.47% / min, p = 0.09. DRI > 1,7 grafts showed a increase risk to test a low ICG-PDR 60 min less than 10 ml/min. (OR: 2,15 95% confidence interval [95% CI], ( 1,07-4,31), p= 0,03. Conclusion DRI considers variables such as elderly donors and prolonged cold ischemia time. Poor quality grafts have a greater susceptibility to ischemia reperfusion damage. A decrases in the measure of intraoperative hepatic artery flow and ICG-PDR could be translating an increase of intrahepatic resistance. To identify grafts “Resistant to Flow” previous to transplant them in new machine perfusion devise could be the aim of posterior studies.

Perioperative Predictors of Acute Kidney Injury after Liver Transplantation and its Impact on Postoperative Outcome

Background and Goal of Study Liver transplantation (LT) is the best treatment for patients with end-stage liver disease. It is a very complex surgery with high rates of morbidity and mortality. Acute kidney injury (AKI) is a common and serious complication after LT. The ability to early identify those patients at high risk of post-LT AKI is crucial, and could provide invaluable help for their proper management during and after LT surgery. The aim of this study was to identify perioperative predictors of post-LT AKI and to assess the impact of AKI on postoperative outcome. Materials and Methods After approval by the Ethical Review Board, we conducted a prospective, single-center study of 242 consecutive adult patients undergoing LT between December 2010 and February 2017. Early AKI was defined according to KDIGO criteria (Kidney Disease Improving Global Outcomes). Serum creatinine was measured at baseline and up to 3 post-LT days. Patients with and without AKI were compared to identify perioperative predictors for this complication. Perioperative variables were collected, including demographic data, baseline creatinine, MELD and Child-Pugh scores, intraoperative hemodynamic data, and transfusion and fluid therapy. Length of intensive care unit (ICU) stay, hospital-stay, 30-day mortality and one-year mortality were studied as postoperative outcomes. For data analysis Man Whitney, Chi-square or Fisher exact tests were used. Results and Discussion The incidence of AKI at 72 h post-LT was 63.6% (154 patients). Only four variables were identified as predictors of post-LT AKI: higher recipient weight, hemodynamic data at end of surgery (cardiac index [CI] and renal perfusion pressure [RPP=mean arterial pressure minus inferior vena cava pressure]) and the amount of intraoperative colloid administration (table 1). The remaining pre- and intra-operative variables did not differ significantly between the two groups. Table. No title available. AKI after liver transplantation was associated with worse post-LT course, with longer ICU and hospital stay, and reduced 30-day and one-year survival (table 2). Table. No title available. Conclusions In patients undergoing LT there was a high incidence of early AKI. Development of AKI after LT was associated with a remarkably worse postoperative outcome. These results suggest that higher intraoperative colloid administration, lower CI and lower RPP had a negative impact on post-LT renal function. Thus, targeting modifiable risk factors, such as fluid therapy and hemodynamic derangements may reduce the incidence of AKI.