Prognostic significance of the controlling nutritional status (CONUT) score in patients undergoing hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis

Background: The clinical value of the controlling nutritional status (CONUT) score in hepatocellular carcinoma (HCC) has increased. The aim of this meta-analysis was to systematically review the association between the CONUT score and outcomes in patients undergoing hepatectomy for HCC. Methods: Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar were systematically searched. Random effects meta-analyses were conducted to examine the prognostic value of the CONUT score in HCC patients. Results: A total of five studies including 4679 patients were found to be eligible and analyzed in the meta-analysis. The CONUT score was significantly associated with overall survival (HR 1.78, 95%CI = 1.20-2.64, P = 0.004, I-2 = 79%), recurrence-free survival (HR 1.34, 95%CI = 1.17-1.53, P Conclusions: The CONUT score is an independent prognostic indicator of the prognosis and is associated with postoperative major complications and hepatic functional reserve in HCC patients

Comparison of three perioperative fluid regimes for laparoscopic donor nephrectomy: A prospective randomized dose-finding study

Background: Pneumoperitoneum (PP), as used for laparoscopic procedures, impairs stroke volume, renal blood flow, glomerular filtration rate and urine output. This study investigated whether perioperative fluid management can abolish these negative effects of PP on hemodynamics. Methods: Twenty-on

A novel difficulty grading system for laparoscopic living donor nephrectomy

Background Several difficulty grading systems have been developed as a useful tool for selecting patients and training surgeons in laparoscopic procedures. However, there is little information on predicting the difficulty of laparoscopic donor nephrectomy (LDN). The aim of this study was to develop a grading system to predict the difficulty of LDN. Methods Data of 1741 living donors, who underwent pure or hand-assisted LDN between 1994 and 2018 were analyzed. Multivariable analyses were performed to identify factors associated with prolonged operative time, defined as a difficulty index with 0 to 8. The difficulty of LDN was classified into three levels based on the difficulty index. Results Multivariable analyses identified that male (odds ratio [OR] 1.69, 95% CI 1.37–2.09, P  28 (OR 1.36, 95% CI 1.08–1.72, P = 0.009), pure LDN (OR 1.99, 95% CI 1.53–2.60, P  Conclusion We developed a novel grading system with simple preoperative donor factors to predict the difficulty of LDN. This grading system may help surgeons in patient selection to advance their experiences and/or teach fellows from simple to difficult LDN

Donor conversion rates depend on the assessment tools used in the evaluation of potential organ donors

Purpose: It is desirable to identify a potential organ donor (POD) as early as possible to achieve a donor conversion rate (DCR) as high as possible which is defined as the actual number of organ donors divided by the number of patients who are regarded as a potential organ donor. The DCR is calculated with different assessment tools to identify a POD. Obviously, with different assessment tools, one may calculate different DCRs, which make comparison difficult. Our aim was to determine which assessment tool can be used for a realistic estimation of a POD pool and how they compare to each other with regard to DCR. Methods: Retrospective chart review of patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage. We applied three different assessment tools on this cohort of patients. Results: We identified a cohort of 564 patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage of whom 179/564 (31.7%) died. After applying the three different assessment tools the number of patients, before exclusion of medical reasons or age, was 76 for the IBD-FOUR definition, 104 patients for the IBD-GCS definition and 107 patients based on the OPTN definition of imminent neurological death. We noted the highest DCR (36.5%) in the IBD-FOUR definition. Conclusion: The definition of imminent brain death based on the FOUR-score is the most practical tool to identify patients with a realistic chance to become brain dead and therefore to identify the patients most likely to become POD

Engaging stimulatory immune checkpoint interactions in the tumour immune microenvironment of primary liver cancers – how to push the gas after having released the brake

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the first and second most common primary liver cancer (PLC). For decades, systemic therapies consisting of tyrosine kinase inhibitors (TKIs) or chemotherapy have formed the cornerstone of treating advanced-stage HCC and CCA, respectively. More recently, immunotherapy using immune checkpoint inhibition (ICI) has shown anti-tumour reactivity in some patients. The combination regimen of anti-PD-L1 and anti-VEGF antibodies has been approved as new first-line treatment of advanced-stage HCC. Furthermore, gemcibatine plus cisplatin (GEMCIS) with an anti-PD-L1 antibody is awaiting global approval for the treatment of advanced-stage CCA. As effective anti-tumour reactivity using ICI is achieved in a minor subset of both HCC and CCA patients only, alternative immune strategies to sensitise the tumour microenvironment of PLC are waited for. Here we discuss immune checkpoint stimulation (ICS) as additional tool to enhance anti-tumour reactivity. Up-to-date information on the clinical application of ICS in onco-immunology is provided. This review provides a rationale of the application of next-generation ICS either alone or in combination regimen to potentially enhance anti-tumour reactivity in PLC patients

Contribution of Type 2 Diabetes Mellitus to Subclinical Atherosclerosis in Subjects with Morbid Obesity

Introduction: Type 2 diabetes mellitus (T2DM) and obesity are both related to increased risk of cardiovascular disease and mortality. Early atherosclerotic vascular changes can be detected by non-invasive tests like carotid artery intima-media thickness (cIMT) and pulse wave velocity (PWV). Both cIMT and PWV are significantly impaired in T2DM patients and in obese patients, but the additional effect of T2DM on these vascular measurements in obese subjects has not been evaluated. Methods: Two hundred morbidly obese patients with or without T2DM were enrolled in a prospective cohort study and underwent extensive laboratory testing, including cIMT and PWV measurements. The cohort was divided into a group with and a group without T2DM. Results: Within this cohort, 43 patients (21.5%) were diagnosed with T2DM. These patients were older and had more often (a history of) hypertension as compared to patients without T2DM. HbA1c levels were significantly increased, while LDL cholesterol was significantly lower and the use of statins higher than in non-diabetic participants. cIMT and PWV were significantly increased in subjects suffering from T2DM. The variability in cIMT and PWV was related to differences in age and systolic blood pressure, but not to the presence of T2DM. Conclusion: While T2DM negatively affects the vasculature in morbid obesity, hypertension and age seem to be the major risk factors, independent from the presence of T2DM. Clinical Trial Registration: Dutch Trial Register NTR5172

Cell-free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers

Background Cell-free microRNAs (miRs) have emerged as early and sensitive biomarkers for tissue injury and function. This study aimed to investigate whether the release of hepatocyte-derived microRNAs (HDmiRs) and cholangiocyte-derived miRs (CDmiRs) correlates with hepato-cholangiocellular injury and function during oxygenated, normothermic machine perfusion (NMP) of human liver grafts. Methods Donor livers (n = 12), declined for transplantation, were subjected to oxygenated NMP (6 hours) after a period of static cold storage (median 544 minutes (IQR 421-674)). Perfusate and bile samples were analyzed by qRT-PCR for HDmiR-122 and CDmiR-222. Spearman correlations were performed between miR levels and currently available indicators and classic markers. Results Both HDmiR-122 and CDmiR-222 levels in perfusate at 30 minutes of NMP strongly correlated with hepatocyte injury (peak perfusate AST) and cholangiocyte injury (peak biliary LDH). In bile, only CDmiR-222 correlated with these injury markers. For hepato-cholangiocellular function, both miRs in perfusate correlated with total bilirubin, while HDmiR-122 (in perfusate) and CDmiR-222 (in bile) correlated with bicarbonate secretion. Both the relative ratio of HDmiR-122/CDmiR-222 and AST in perfusate at 30 minutes significantly correlated with cumulative bile production, but only the relative ratio was predictive of histopathological injury after 6 hours NMP. Conclusion Early levels of HDmiR-122 and CDmiR-222, in perfusate and/or bile, are predictive of excretory functions and hepato-cholangiocellular injury after 6 hours NMP. These miRs may represent new biomarkers for graft viability and function during machine perfusion

Successful adult domino living donor liver transplantation in methylmalonic acidemia:case report

Background: Liver transplantation (LT) is a therapeutic option in multiple inherited metabolic diseases (IMDs), including methylmalonic acidemia (MMA), as LT reduces the risk of acute metabolic decompensations and long-term complications associated with these diseases. In certain IMDs, such as maple syrup urine disease (MSUD), domino liver transplant (DLT) is an accepted and safe method which expands the donor pool. However, only one adult case of DLT using an MMA donor liver has been reported; outcome and safety are still unknown and questioned. Case Description: In this case report, we describe our experience with DLT using MMA livers. Two adult MMA patients underwent living donor liver transplant (LDLT); their MMA livers were consecutively transplanted into two patients on the liver transplant waiting list who had limited chance of receiving a liver transplant in the short term due to their low model for end-stage liver disease (MELD) scores. No severe peri- or postoperative complications occurred, however the recipients of the MMA livers biochemically now have mild MMA. Conclusions: DLT using MMA grafts is a feasible strategy to treat end-stage liver disease and expand the donor organ pool. However, the recipient of the MMA domino liver may develop mild MMA which could affect quality of life, and long-term safety remains unclear. Further long-term of outcomes for domino recipients of MMA livers, focusing on quality of life and any metabolic complications of transplantation are needed to better define the risks and benefits

Starting a Crossover Kidney Transplantation Program in The Netherlands: Ethical and Psychological Considerations

On April 15th, 2003, the first crossover kidney transplantation took place in The Netherlands. In September of the same year, a national database was established to facilitate kidney exchange between two donor-recipient couples. During 2004, kidneys from living donors will be exchanged between the seven university medical centers in The Netherlands. One of the conditions for successfully implementing this program was the need to address the ethical and psychologic implications involved. In this article we will discuss the ethical and psychologic considerations that are accompanying the practical preparations for the first Dutch crossover transplantation program. We identified five topics of interest: the influence of "donation by strangers" on the motivation and willingness of donor-patient couples, the issue of anonymity, the loss of the possibility of "medical excuses" for unwilling donors, the view that crossover is a first step to commercial organ trade, and the interference with existing organ donation programs. We concluded that whether viewed separately or in combination, these issues do not impede the efficient organization of a crossover program or raise worrying ethical issues. Key Words: Ethics, psychology, crossover transplantation, kidney exchange program. 2004;78: 194 -197) T he Netherlands has a population of 16 million. Approximately 375 to 425 kidneys per year are transplanted from cadaver donors. In addition to cadaver transplants, approximately 200 kidneys from living donors were transplanted during 2003. Although the growing number of available living donors helps prevent the waiting lists from growing further, there are not enough kidneys available to help the 1,300 patients already on the waiting list. After starting dialysis, kidney patients have an average waiting time of 4 years before a kidney becomes available. In the meantime, their health status declines. Currently, the mortality rate of patients on dialysis is approximately 20% per year (1). (Transplantation Living organ donation by family or friends offers an opportunity to reduce the long waiting lists. However, in a third of these cases, the transplantation cannot take place because of ABO incompatibility or donor-specific sensitization (2). A crossover transplantation program offers new hope. The program provides a lifesaving opportunity when a donor cannot give his or her kidney to his or her recipient. If another donor-recipient couple experiences the same problem, the kidneys can be exchanged. In South Korea, such a crossover kidney exchange program has been operating successfully for more than 10 years (3). The United States also has experience with "kidney swapping" (4). In Europe, however, crossover transplantations have been attempted only once in Switzerland, in Romania, and in Rotterdam. This conservative European attitude is in part explained by concerns surrounding the ethical and psychologic implications of crossover transplantation. When a crossover program was initiated in The Netherlands, it was agreed that these concerns should be addressed. A multidisciplinary research effort was conducted to determine the most prominent psychologic and ethical issues that surround crossover kidney exchange and to propose practical solutions. We identified five topics of interest: (1) the influence of "donation by strangers" on the motivation and willingness of donor-patient couples; (2) the issue of anonymity; (3) the loss of the possibility of "medical excuses" for unwilling donors; (4) the view that crossover might be the first step to commercial organ trade; and (5) the interference with existing organ donation programs. Next we describe these five topics in detail and suggest practical solutions. Living Organ Donation by Strangers When discussing the ethical and psychologic issues of a crossover transplantation program, a prominent issue is the possibility of a difference in motivation and willingness of kidney donors and recipients compared with the attitudes of those involved in a direct living donation program. At first glance, crossover donation between two couples is not significantly different from direct living kidney donation. The motivation of the donor is the same: helping a friend or a family member by giving a kidney. The result for the patient is equivalent as well: He or she receives the much needed organ. Furthermore, the medical impact for the four people involved is the same as for the two direct living kidney donors. Psychologically, however, it might matter for those involved whethe