Major liver resections, perioperative issues and posthepatectomy liver failure: A comprehensive update for the anesthesiologist.

Significant advances in surgical techniques and relevant medium- and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections. To support these outstanding results and to reduce perioperative complications, anesthesiologists must address and master key perioperative issues (preoperative assessment, proactive intraoperative anesthesia strategies, and implementation of the Enhanced Recovery After Surgery approach). Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate. Among postoperative complications, posthepatectomy liver failure (PHLF) occurs in different grades of severity (A-C) and frequency (9%-30%), and it is the main cause of 90-d postoperative mortality. PHLF, recently redefined with pragmatic clinical criteria and perioperative scores, can be predicted, prevented, or anticipated. This review highlights: (1) The systemic consequences of surgical manipulations anesthesiologists must respond to or prevent, to positively impact PHLF (a proactive approach); and (2) the maximal intensive treatment of PHLF, including artificial options, mainly based, so far, on Acute Liver Failure treatment(s), to buy time waiting for the recovery of the native liver or, when appropriate and in very selected cases, toward liver transplant. Such a clinical context requires a strong commitment to surgeons, anesthesiologists, and intensivists to work together, for a fruitful collaboration in a mandatory clinical continuum.

Robotic Versus Laparoscopic Donor Nephrectomy: A Retrospective Bicentric Comparison of Learning Curves and Surgical Outcomes From 2 High-volume European Centers.

BACKGROUND: Although laparoscopic donor nephrectomy (LDN) represents the gold-standard technique for kidney living donation, robotic donor nephrectomy (RDN) settled as another appealing minimally invasive technique over the past decades. A comparison between LDN and RDN outcomes was performed. METHODS: RDN and LDN outcomes were compared, focusing on operative time and perioperative risk factors affecting surgery duration. Learning curves for both techniques were compared through spline regression and cumulative sum models. RESULTS: The study analyzed 512 procedures (154 RDN and 358 LDN procedures) performed between 2010 and 2021 in 2 different high-volume transplant centers. The RDN group presented a higher prevalence of arterial variations (36.2 versus 22.4%; P = 0.001) compared with the LDN cohort. No open conversions occurred; operative time (210 versus 195 min; P = 0.011) and warm ischemia time (WIT; 230 versus 180 s; P < 0.001) were longer in RDN. Postoperative complication rate was similar (8.4% versus 11.5%; P = 0.49); the RDN group showed shorter hospital stay (4 versus 5 d; P < 0.001). Spline regression models depicted a faster learning curve in the RDN group ( P = 0.0002). Accordingly, cumulative sum analysis highlighted a turning point after about 50 procedures among the RDN cohort and after about 100 procedures among the LDN group.Higher body mass index resulted as an independent risk factor for longer operative time for both techniques; multiple arteries significantly prolonged operative time in LDN, whereas RDN was longer in right kidney procurements; both procedures were equally shortened by growing surgical experience. CONCLUSIONS: RDN grants a faster learning curve and improves multiple vessel handling. Incidence of postoperative complications was low for both techniques.

Location and allocation: Inequity of access to liver transplantation for patients with severe acute-on-chronic liver failure in Europe.

There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF-3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3, between 2018 and 2019 were included across 20 transplantation centers. A total of 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted patients with ACLF-3 admitted to the ICU and the number listed or transplanted while in ACLF-3 across centers. By contrast, there was a correlation between the number of patients listed and the number transplanted while in ACLF-3. About 21% of patients who were listed while in ACLF-3 died on the waiting list or were delisted. The percentage of LT for patients with ACLF-3 varied from 0% to 29% for those transplanted with decompensated cirrhosis across centers (average = 8%), with an I2 index of 68% (95% confidence interval, 49%-80%), showing substantial heterogeneity among centers. The 1-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more patients with ACLF-3 (>10 patients) than in centers that listed and transplanted fewer: 36% versus 20%, respectively (p = 0.012). Patients with ACLF-3 face inequity of access to LT across Europe. Waitlisting strategies for patients with ACLF-3 influence their access to LT and, ultimately, their survival.

Obstructive Uropathy Due to an Unusual Inguinal Hernia 35 Years After Kidney Transplant.

In a kidney transplant recipient, bladder and graft ureter displacement into a groin hernia is a highly unusual cause of obstructive uropathy that may lead to graft dysfunction or graft loss. We report the case of a White man, 56 years old, who had previously, at the age of 19 years, undergone a kidney transplant from a deceased donor, to mitigate chronic glomerulonephritis. The patient presented to us with a reducible left inguinal hernia with worsening kidney function, and we used the Lichtenstein hernioplasty technique to surgically repair the hernia, which was followed by an uneventful postoperative course. Existing literature has identified few cases of kidney graft dysfunction due to inguinal hernias. Groin hernia repair of this type in this specific circumstance remains a subject of debate. However, in our opinion, with attention to appropriate reductions of immunosuppressive therapy, the Lichtenstein technique is safe for transplant recipients and the use of mesh greatly reduces the risk of hernia recurrence.

Kidney Transplants From Donors on Extracorporeal Membrane Oxygenation Prior to Death Are Associated With Better Long-Term Renal Function Compared to Donors After Circulatory Death.

Donation after circulatory death (DCD) allows expansion of the donor pool. We report on 11 years of Italian experience by comparing the outcome of grafts from DCD and extracorporeal membrane oxygenation (ECMO) prior to death donation (EPD), a new donor category. We studied 58 kidney recipients from DCD or EPD and collected donor/recipient clinical characteristics. Primary non function (PNF) and delayed graft function (DGF) rates, dialysis need, hospitalization duration, and patient and graft survival rates were compared. The estimated glomerular filtration rate (eGFR) was measured throughout the follow-up. Better clinical outcomes were achieved with EPD than with DCD despite similar graft and patient survival rates The total warm ischemia time (WIT) was longer in the DCD group than in the EPD group. Pure WIT was the highest in the class II group. The DGF rate was higher in the DCD group than in the EPD group. PNF rate was similar in the groups. Dialysis need was the greatest and hospitalization the longest in the class II DCD group. eGFR was lower in the class II DCD group than in the EPD group. Our results indicate good clinical outcomes of kidney transplants from DCD despite the long "no-touch period" and show that ECMO in the procurement phase improves graft outcome, suggesting EPD as a source for pool expansion.

Preoperative risk score for prediction of long-term outcomes after hepatectomy for intrahepatic cholangiocarcinoma: Report of a collaborative, international-based, external validation study.

PURPOSE: A preoperative risk score (PRS) to predict outcome of patients with intrahepatic cholangiocarcinoma treated by liver surgery could be clinically relevant.To assess accuracy for broadly adoption, external validation of predictive models on independent datasets is crucial. The objective of this study was to externally validate the score for prediction of long-term outcomes after liver surgery for intrahepatic cholangiocarcinoma proposed by Sasaki et al. and based on preoperative albumin, neutrophil-to-lymphocytes-ratio, CA19-9 and tumor size. METHODS: Patients treated by liver surgery for intrahepatic cholangiocarcinoma at 11 international HPB centers from 2001 to 2018 were included in the external validation cohort. Harrell's c-index and Hosmer-Lemeshow analyses were used to test PRS discrimination and calibration. Kaplan-Meier curve for risk groups as described in the original study were displayed. RESULTS: A total of 355 patients with 174 deaths during the follow-up period (median = 41.7 months, IQR 32.8-50.6) were included. The median PRS value was 14.7 (IQR 10.7-20.6), with normal distribution across the cohort. A Cox regression on PRS covariates found coefficients similar to those of the derivation cohort, except for tumor size. Measures of discrimination estimated by Harrell's c-index was 0.61(95%CI:0.56-0.67) and Hosmer-Lemeshow p = 0.175. The Kaplan-Meyer estimation showed reasonable discrimination across risk groups, with 5years survival rate ranging from 20.1% to 0%. CONCLUSION: In this external validation cohort, the PRS had mild discrimination and poor calibration performance, similarly to the original publication. Nevertheless, its ability to identify different classes of risk is clinically useful, for a better tailoring of a therapeutic strategy.

Renal Transplants from Older Deceased Donors: Use of Preimplantation Biopsy and Differential Allocation to Dual or Single Kidney Transplant according to Histological Score Has No Advantages over Allocation to Single Kidney Transplant by Simple Clinical Indication.

BACKGROUND: Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. METHODS: A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKTpre) on clinical grounds alone (before Dec 2010, pre-DKT era, n = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, n = 132) to DKT (n = 48), SKT biopsy-based protocol ("high-risk", SKThr, n = 51), or SKT clinically based protocol ("low-risk", SKTlr, n = 33). Graft and patient survival were compared between the two periods and between different transplant categories. RESULTS: Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60-69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKThr showed worst graft and overall survival in the 60-69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. CONCLUSIONS: Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.

Does the Pringle maneuver affect survival and recurrence following surgical resection for hepatocellular carcinoma? A western series of 441 patients.

BACKGROUND: The impact of the Pringle maneuver (PM) on long-term outcome after curative resection for hepatocellular carcinoma (HCC) is controversial, with eastern series reporting conflicting results. We aim to evaluate the impact of the PM in a western cohort. METHODS: We retrospectively analyzed patients with HCC who underwent liver resection between January 2001 and August 2015. Patients were divided in two groups based the use of the PM during resection. Primary outcomes were overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 441 patients were analyzed. Of these, 176 patients (39.9%) underwent PM. Median OS was 46.4 months (95%CI: 34.1-58.7) for the PM group and 56.5 months (95%CI: 37.1-75.9) for the no-PM group (P = 0.188), with a median DFS of 26.7 months (95%CI: 15.7-37.7) and 24.9 months (95%CI: 18.1-31.7), respectively (P = 0.883). CONCLUSIONS: These results suggest that PM does not increase the risk of tumor recurrence or decrease long-term survival.

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

BACKGROUND: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. METHODS: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. RESULTS: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). CONCLUSIONS: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.

Donor safety in living donor liver donation: An Italian multicenter survey.

Major concerns about donor morbidity and mortality still limit the use of living donor liver transplantation (LDLT) to overcome the organ shortage. The present study assessed donor safety in LDLT in Italy reporting donor postoperative outcomes in 246 living donation procedures performed by 7 transplant centers. Outcomes were evaluated over 2 time periods using the validated Clavien 5-tier grading system, and several clinical variables were analyzed to determine the risk factors for donor morbidity. Different grafts were obtained from the 246 donor procedures (220 right lobe, 10 left lobe, and 16 left lateral segments). The median follow-up after donation was 112 months. There was no donor mortality. One or more complications occurred in 82 (33.3%) donors, and 3 of them had intraoperative complications (1.2%). Regardless of graft type, the rate of major complications (grade ≥ 3) was 12.6% (31/246). The overall donor morbidity and the rate of major complications did not differ significantly over time: 26 (10.6%) donors required hospital readmission throughout the follow-up period, whereas 5 (2.0%) donors required reoperation. Prolonged operative time (>400 minutes), intraoperative hypotension (systolic < 100 mm Hg), vascular abnormalities, and intraoperative blood loss (>300 mL) were multivariate risk factors for postoperative donor complications. In conclusion, from the standpoint of living donor surgery, a meticulous and well-standardized technique that reduces operative time and prevents blood loss and intraoperative hypotension may reduce the incidence of donor complications. Transparency in reporting results after LDLT is mandatory, and we should continue to strive for zero donor mortality. Liver Transplantation 23 184-193 2017 AASLD.

[Surgical overview on kidney and pancreas transplantation]. / Problemi chirurgici nel trapianto di rene e di pancreas - Position paper.

The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed.

Robotic nephrectomy for living donation: surgical technique and literature systematic review.

BACKGROUND: As compared with traditional laparoscopy, robotic-assisted surgery provides better EndoWrist instruments and three-dimensional visualization of the operative field. Studies published so far indicate that living donor nephrectomy using the robot-assisted technique is safe, feasible, and provides remarkable advantages for the patients. METHODS: From 5 papers reporting detailed descriptions of surgical technique for robotic assisted nephrectomy (RAN) in living donor kidney transplantation, we have gathered information about the surgical techniques as well as about patients' intra- and postoperative outcome. Data from these articles were analyzed together with the data from our own experience (33 cases) so that the total number of analyzed cases was 292. RESULTS: In the analyzed populations, no case of donor death occurred, and no case developed complication above grade 2 of Clavien score. Perioperative complications occurred in 37 of the 292 patients (12.6%). Accidental acute hemorrhage occurred in 5 of the 292 cases (1.7%). The average overall intraoperative blood loss was 67.8 mL (range 10 to 1,500). The average warm ischemia time was 3.5 minutes (range .58 to 7.6). Conversion to the open technique occurred in only 4 cases (1.3%). The average overall operative time was 192 minutes (range 60 to 400). The average length of the hospital stay was 2.7 days (range 1 to 10). CONCLUSIONS: Safety and feasibility of RAN are pointed out in all the reviewed article, both as hand-assisted and as totally robotic technique. RAN appears to be significantly easier for the surgeons and the results are comparable with the ones obtained with the pure laparoscopic technique.

Current status and perspectives in split liver transplantation.

Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure.

Repeat Hepatectomy for Recurrent Colorectal Liver Metastases: Is it Worth the Challenge?

INTRODUCTION: Repeat hepatectomy (RH) is considered a valuable option for management of recurrent colorectal liver metastases (R-CLM). Here, the outcome of RH for R-CLM was compared to that of patients who underwent single hepatectomy (SH) after subdividing the later according to re-recurrence status. METHODS: Between 2001 and 2013, patients who received hepatectomy for CLM and R-CLM were included in study. Patients with non-resectable R-CLM were excluded. RESULTS: One hundred sixteen patients were included: 86 patients in SH group and 30 patients in RH group. Repeat hepatectomy group had more synchronous CLM (76.7 versus 50 %, p = 0.011). From the 86 patients who underwent SH, 69 patients did not have R-CLM. Survival analysis was done from the time of first hepatectomy for the no R-CLM group and the time of RH for the RH group. The 3- and 5-year survival rates for the no R-CLM group were 66.4 and 48.8%, respectively, and for the RH group were 56 and 44.8% respectively (p = 0.841). Multivariate analysis showed that larger size of R-CLM is an independent risk factor for survival after RH. CONCLUSION: Repeat hepatectomy for R-CLM shows a comparable OS to non-recurrent CLM after single hepatectomy, despite the RH group had higher incidence of synchronous CLM.

Survival after Liver Transplant: Influence of Progression of Disease and of Restoration of the "Milan" Criteria in Patients with Hepato-cellular Carcinoma undergoing Down-staging Procedures.

BACKGROUND/AIMS: Selection of patients with hepa- to-cellular carcinoma for liver transplantation is gen- erally performed according to the so-called Milan cri- teria. The aim of this study was to learn whether, after down-staging loco-regional therapies, patients origi- nally non-fulfilling the MC (Milan-OUT) meet these criteria (Milan-IN). METHODOLOGY: Between January 2000 and December 2008, 172 patients with HCC re- ceived LT at our Department. Of these, 142 were sub- jected to DS before LT. RESULTS: Of the 142 patients who received DS, 115 (81%) were Milan-IN and 27 (19%) were Milan-OUT at the time of their enrollment in the waiting list for LT. After a median follow-up of 50 months, overall 1-, 3-, and 5-year survival and dis- ease recurrence-free survival were not significantly different. CONCLUSIONS: Patients with Milan-OUT HCC can be successfully subjected to LT when they fulfill the MC after being subjected to DS. Imaging progres- sion while on the waiting list is a strong predictor of high rates of HCC recurrence even in patients meet- ing the MC. Lack of imaging progression seems to be a strong predictor of positive LT outcome and should be added to the eligibility criteria for the assessment of LT candidates with HCC.

The role of adult living donor liver transplantation and recent advances.

Twenty years since the first cases were described, adult living donor liver transplantation (ALDLT) is now considered a valid option to expand the donor pool in view of the ongoing shortage of organs and the high waiting list mortality rate. Despite the rapid evolution and acceptance of this complex process of donation and transplantation in clinical practice, the indications, outcome, ethical considerations and quality and safety aspects continue to evolve based on new data from large cohort studies. This article reviews the surgical and clinical advances in the field of liver transplantation, focusing on technical refinements and discussing the issues that may lead to a further expansion of this complex surgical procedure and the role of ALDLT.

Residual right portal branch flow after first-step ALPPS: artifact or homeostatic response?

BACKGROUND/AIMS: Mutual interactions between portal vein and hepatic artery can be documented during hepatobiliary surgery. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a recently introduced surgical technique which can also represent a unique living human model to investigate intrahepatic blood circulation. We report three consecutive cases in which a residual right portal branch flow was clearly detectable after first-step ALPPS, and try to further investigate this unexpected finding with intraoperative clamping tests. METHODOLOGY: Every patient was evaluated with CT scan 7 days after first-step ALPPS and Intraoperative Doppler Ultrasonography (IOUS) at both steps of the procedure. RESULTS: In every patient, CT scan and second-step IOUS demonstrated a clear hepatopetal flow distally to the divided right portal branch. The flow was present after right biliary duct clamping and stopped after right total hilar clamping as well as after right hepatic artery occlusion. CONCLUSIONS: Neither cross-portal circulation between the two hemilivers nor trans-sinusoidal backflow from the hepatic veins can explain these findings, which are rather consistent with a refilling of the occluded portal branch through the opening of intrahepatic arterioportal shunts (APS). APS could represent the simplest homeostatic mechanism that regulate intrahepatic blood flow.