A proposal for scoring marginal liver grafts

The aim of this study is to assess the effect of accumulation of marginal liver graft criteria on the immediate outcome of liver transplantation (LT). The last 325 consecutive LT performed in 293 patients were analyzed retrospectively with respect to donor acceptance criteria. A marginal liver score was elaborated on the basis of the following features: donor > 60 years, ICU stay > 4 days, cold ischemia times > 13 h, hypotensive episodes < 60 mmHg > 1 h, bilirubin > 2.0 mg/dl, ALT > 170 U/l, and AST > 140 U/l were scored with the value 1. The use of dopamine doses > 10 μ/kg per min and peak serum sodium > 155 mEq/l were labeled with value 2. The cut-off point at 6 months after LT revealed 42 deaths (14 %), with 65 graft losses (20 %) and 32 (9 %) retransplants. Recipient survival was not affected by the combined effect of marginal criteria. However, recipients transplanted with marginal livers with score 3 or more showed a decrease in graft survival (log-rank 6.21; P = 0.045) and an increase in delayed non-function rate (10 out of 33 vs 4 out of 156; P = 0.03). The use of marginal liver donors with more than three risk factors must be carefully reviewed or refused because of the cumulative dysfunction of these grafts.     

Donor liver dysfunction: application of a new scoring system to identify the marginal donor

Livers from marginal donors are increasingly used for transplantation due to the shortage of donor organs. The definition of a marginal donor remains unclear; prediction of organ function is a challenge. In the literature the use of steatotic livers has been associated with poor liver function or even primary dysfunction of the allograft. Tekin et al created a scoring system that classifies a donor as marginal or nonmarginal, using a mathematical model based on donor age and steatosis degree. The aims of this study were to apply the Tekin method to identify marginal and nonmarginal donors and evaluate the influence of the cold ischemia time (CIT) on allograft evolution. We retrospectively reviewed deceased donor liver transplantations performed from October 1995 to March 2006, namely, 177 adult liver transplantations in 163 patients. Fifty-five were excluded due to retransplantation (14) or insufficient data (41). Donor age and macrovesicular steatosis were evaluated according to the mathematical formula proposed by Tekin et al, classifying the donors as marginal versus nonmarginal. The authors also analyzed the CIT, 3-month mortality, and development of primary nonfunction or primary dysfunction. The median donor age was 38.9 years (range, 6-71). The postreperfusion biopsy specimen showed moderate to intense steatosis (>30%) in 14.75% of specimens, with no steatosis or mild steatosis in 85.25%. Sixty-one grafts (50%) developed primary graft dysfunction (PGD): 10 grafts, with primary nonfunction (PNF); and 51 with initial poor function (IPF). Using the criteria provided by Tekin et al, we obtained 41 marginal and 81 nonmarginal allografts. The marginal group showed 61.9% PGD, compared with 59.2% of PGD by the nonmarginal group. The CIT was greater than 12 hours in 5 marginal group transplants and 4 PGD cases (80%). Of the nonmarginal allografts, the CIT was greater than 12 hours in 29.6%, with 75% PGD. The 3-month graft survival rate was 80% in the marginal group with ischemia time more than 12 hours: 86.1% of the same group when CIT was less than 12 hours, and 82.7% in the nonmarginal group. In contrast, when we analyzed the occurrence of allograft dysfunction, the 3-month mortality rate was 34% among, grafts with dysfunction, whereas, in those without initial dysfunction, it was 4.1%. In conclusion, the score suggested by Tekin et al that classifies the donors as ideal (nonmarginal) or marginal was not able to predict initial primary dysfunction.     

Influence of marginal donors on liver preservation injury

PURPOSE: The purpose of this study was to assess the accumulated effects of marginal donor quality factors on liver preservation injury (LPI). METHODS: The most recent 400 consecutive liver transplantations at our institution were reviewed. Marginal liver donor criteria included the following: older than 60 years, an intensive care unit stay under ventilatory support for more than 4 days, a cold ischemia time more than 14 hr, high inotropic drug use, prolonged hypotensive episodes for more than 1 hr and less than 60 mm Hg, a peak serum sodium more than 155 mEq/L, and high levels of bilirubin, alanine transferase, or amino transferase. The type of steatosis (macrovesicular or microvesicular) was quantified in four categories: no steatosis, mild (<30%), moderate (30-60%), and severe (> 60%). LPI was stratified histologically in four levels: no damage, mild, moderate, and severe injury. These variables were included in a logistic regression analysis for prediction of the probability of the appearance of LPI. RESULTS: Five variables showed an independent influence on LPI: high inotropic drug use (odds ratio [OR]=1.56), donor age (OR=1.017 per year), moderate to severe macrovesicular steatosis (OR=3.63), cold ischemia time (OR=1,109 per hour), and prolonged stay in an intensive care unit (OR=1.79). Severe LPI was present in 32.7% of the grafts from donors without any factor of the model; in 46.8% from donors with one factor (P =0.09); in 66.2% from donors with two factors (P =0.006); and in 78.3% from donors with at last three factors (P =0.002) (global P=0.0001; chi2 =21.8). CONCLUSIONS: LPI can be potentially predicted based on donor and graft conditions. Accumulation of factors is correlated with an increased effect on LPI.     

Expanded criteria donors, histological scoring, and prolonged cold ischemia: impact on renal graft survival

The use of expanded donors or kidneys with preexistent chronic damage remains controversial, but they offer the opportunity to expand the donor pool. We investigated the impact of these conditions as predictors of graft survival among a cohort of recipients with prolonged cold ischemia times and a high incidence of delayed graft function. We included 70 consecutive cadaveric kidney allografts implanted between 2001 and 2005, which had undergone an early graft biopsy. Delayed graft function was present in 84% of cases with moderate or severe preexistent chronic damage in 63% and 27% of biopsies, respectively, and acute rejection was diagnosed in 14.3% of overall cases. The graft survival was 73.3% at 48 months. Primary nonfunctioning kidneys were more frequent using kidneys from expanded compared with standard donors (20.0% vs 0.0%, P < .002). Multivariate analysis showed that only the donor condition (standard vs expanded) was independently associated with graft survival (hazard ratio: 0.12; 95% confidence interval: 0.01-0.87; P < .03). Our results suggested that the donor characteristics prevail over other variables to predict graft outcomes.     

A simple scoring system to reduce the negative appendicectomy rate.

In a controlled, prospective study the following five criteria were used for the diagnosis and management of acute appendicitis: abdominal pain; vomiting; right lower quadrant tenderness; low grade fever (< or = 38.8 degrees C); and polymorphonuclear leucocytosis (TC > or = 10,000 with polymorphs > or = 75%). The aim of the study was to reduce the negative appendicectomy rate. If four out of five or five out of five criteria were present on admission, appendicectomy was carried out. On the other hand, if three out of five criteria were present on admission, the patient was subjected to active inpatient observation until either the development of the fourth criterion, when appendicectomy was performed, or until the patient recovered and the condition did not progress beyond the third criterion. Generalised peritonitis due to a perforated appendix was excluded from the study. Over a 1-year period, 58 patients (M:F = 45:13) were entered into the study. Appendicectomy was carried out in 46 (80%) of patients; of these, 32 patients (70%) were operated on soon after admission. The remaining 14 (30%) were operated on after a period of inpatient observation decided the development of the fourth criterion. A total of 12 patients (12/58 = 20%) did not undergo operation. The control group consisted of 59 patients upon whom appendicectomy was carried out by another surgical unit over the same 1-year period. The negative appendicectomy rate in the trial group was 6.5% (3/46), whereas in the control group it was 17% (10/59) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Introducing a new, simple scoring system to evaluate oncological and functional outcome after radical prostatectomy

OBJECTIVE: To create a scoring system which takes into account oncological outcome and functional results (continence and erectile function) of patients after radical prostatectomy. MATERIAL AND METHODS: A total of 146 consecutive men underwent radical prostatectomy for localized prostate cancer and were evaluated 1 year after surgery. Biochemical recurrence was defined as a single postoperative prostate-specific antigen (PSA) level of > 0.2 ng/ml. Continence, defined as not using a pad, and potency, defined as the ability to achieve and maintain an erection suitable for sexual intercourse, were evaluated by means of a prospective, self-administered questionnaire. Each patient received 4 points (if PSA was <0.2 ng/ml) or 0 points (if PSA was >0.2 ng/ml) for oncological outcome, 2 points (if continent) or 0 points (if incontinent) for urinary continence and 1 point (if potent) or 0 points (if impotent) for erectile function. The total score was calculated, with higher scores indicating a better outcome. The unique feature of this scoring system is that each individual score represents a particular clinical status regarding oncological and functional outcome. RESULTS: One year after surgery, 121 (82.8%) patients had PSA levels of <0.2 ng/ml, 103 (70.5%) were continent and 53 (36.3%) were potent. Patients with a total score of > or =4 points had good cancer control and could be further subdivided into those who were continent and potent (7 points; 22.6%), those who were continent but had erectile dysfunction (ED) (6 points; 34.2%), those who were incontinent and potent (5 points; 8.2%) and those who were incontinent and had ED (4 points; 17.8%). Similarly, patients with a score of <4 points had no cancer control and could be further subdivided into those who were continent and potent (3 points; 3.4%), those who were continent but had ED (2 points; 10.3%), those who were incontinent and potent (1 point; 2.1%) and those who were incontinent and had ED (0 points; 1.3%). CONCLUSIONS: This scoring system includes the three most important outcomes after radical prostatectomy, namely cancer control, continence and erectile function. It may allow us to better evaluate, communicate and compare the results of radical prostatectomy in a multinational, multicenter setting.     

The use of marginal donors for liver transplantation. A retrospective study of 365 liver donors.

A total of 365 donor hepatectomies performed between May 1985 and March 1990 were reviewed and analyzed retrospectively to identify risk factors associated with poor graft function and to study the outcome of grafts retrieved from "marginal" donors. The donor mean age was 27.1 years (8-69 years). Mean ICU donor stay was 2.7 days (range 0 to 18 days), and the mean ischemic time was 8.6 hr (range 3 to 22 hr). The pancreas was retrieved in 39 donors. Donor's weight above 100 kg was the only variable found to be associated with both significantly increased 3-month graft loss (P less than 0.01) and early hepatocellular damage--AST or ALT greater than 2000 U/ml, 1st day posttransplant (P less than 0.02). Prolonged stay in the ICU (greater than 3 days), although associated with a significantly increased rate of hepatocellular damage (P less than 0.05), did not affect early graft survival. A systolic blood pressure less than 90 mmHg despite the use of high-dose dopamine (greater than 15 micrograms/mg/min), but not each of these variables itself, was also associated with a significantly increase rate of hepatocellular damage (P less than 0.001). All other variables, including age greater than 50, ischemic time greater than 12 hr, combined liver-pancreas procurement, and liver function test abnormalities, did not affect the outcome. We conclude that extending our limits to accept donors of the higher age group and those who have moderately abnormal liver function tests or a prolonged ischemic time will not jeopardize our results. It is suggested to perform liver biopsy in overweight donors during the retrieval to prevent using grafts with severe fatty infiltration. It is hypothesized that hormonal changes, starvation, and increased risk to develop infection might jeopardize the outcome of grafts from donors with a prolonged ICU stay. Although 70% of the early hepatocellular injuries are reversible, the remaining 30% result in graft failure.     

The utility of marginal donors in liver transplantation

The shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. The combination of multiple marginal factors seems to be additive on graft injury. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described, including older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with malignancies. The pathophysiology of the marginal donor will be discussed, along with strategies for minimizing the ischemia reperfusion injury experienced by these organs. Finally, new strategies for improving the function of the marginal/expanded donor liver will be reviewed. (Liver Transpl 2003;9:651-663.)     

The effects of fasting on the quality of liver preservation by simple cold storage

Although livers can be successfully preserved for 24 hr or more, often the transplanted livers have poor or no (primary nonfunction) function. The quality of the liver does not appear dependent upon the time of preservation but may be dependent upon the condition of the donor. In this study we have investigated the effects of fasting on the quality of livers for transplantation. Rabbits were fasted (48 hr) and livers preserved in the UW solution for 6-8 hr. Functions of the liver were analyzed by isolated perfusion for 2 hr. Also, pigs were fasted for 72 hr, livers preserved for 12 hr, and viability determined by orthotopic transplantation. Fasting depleted the liver glycogen by 85% but had no effect on ATP or glutathione concentrations. Rabbit livers from fasted animals produced similar amounts of bile, released similar concentrations of lactate dehydrogenase (LDH) and aspartate amino transaminase (AST) into the perfusate, maintained similar concentrations of ATP and glutathione in the tissue, and had a similar intracellular K:Na ratio after 24-hr preservation when compared to livers from fed animals. After 48-hr preservation, livers from fasted animals were less viable than livers from fed animals, including: reduced bile production (2.0 +/- 0.3 vs. 5.0 +/- 0.9 ml/2 hr, 100 g), greater release of LDH (3701 +/- 562 units vs. 1123 +/- 98 units) and AST, less ATP (0.326 +/- 74 vs. 0.802 +/- 160 nmol/g), less glutathione (0.303 +/- 13 vs. 0.933 +/- 137 nmol/g), and a lower K:Na ratio (1.5 +/- 0.9 vs. 7.4 +/- 0.6). Pigs receiving livers from fed animals preserved for 12 hr had better survival (5/6, 83%) than livers from fasted animals (3/6, 50%). The results show that the nutritional status of the donor can affect the outcome of liver preservation and transplantation. Increased injury in livers from fasted animals may be due to the loss of glycogen that may be an essential source of energy in the initial posttransplant period. In clinical liver transplantation the nutritional status of the donor may be an important factor in the initial function of the liver, and methods to increase the nutritional status of the donor may be important in increasing the quality of livers.     

供肝热缺血后对冷保存的耐受时限初步探讨

目的探讨供肝热缺血后耐受冷保存的安全时限。方法利用本组所建立的小型猪肝移植模型,设定供肝热缺血时间为20min,根据在UW液中的冷保存时间不同分为3组,分别冷保存12、16、20h,于肝移植术中及术后检测肝功能、肝脏病理、肝组织ATP含量、移植肝脏再灌注后微循环血流量及动物术后1周存活率。结果UW液冷保存12h组肝移植后小型猪1周内全部存活,而冷保存16、20h组存活率分别为20%、0%;随着冷保存时间的从12h延长到20h,ALT、AST逐渐上升,肝脏ATP含量、肝脏微循环血流量逐渐下降,形态学结果显示肝组织细胞变性、坏死及超微结构损害的程度逐渐加重。冷保存12h组与后两组上述指标存在显著性差异,生化及肝脏微循环指标的改变与病理结果及动物生存率相符合。结论在本实验条件下,热缺血时间为20min的供肝耐受冷保存的安全时限约为12h。     

Contribution of marginal donors to liver transplantation for hepatitis C virus infection

The use of marginal liver donors can affect the outcomes of liver transplantation in patients with hepatitis C virus (HCV) infection. There are no firm conclusions about which donor criteria are important for allocation of high-risk grafts to recipients with HCV cirrhosis. We performed 120 consecutive liver transplantations for HCV infection between 1995 and 2005. Marginal donor criteria were considered to be: age >70 years, macrovesicular steatosis >30%, moderate-to-severe liver preservation injury, high inotropic drug dose (dopamine >15 microg/kg/min; epinephrine, norepinephrine, or dobutamine at any doses), peak serum sodium >155 mEq/L, any hypotensive episode <60 mm Hg and >1 hour, cold ischemia time >12 hours, ICU hospitalization >4 days, bilirubin >2 mg/dL, AST and/or ALT >200 UI/dL. Graft survival with donors showing these marginal criteria was compared with optimal donors using Kaplan-Meier analysis and the log-rank test. Independent predictors of survival were computed with the Cox proportional hazards model. Fifty-six grafts (46%) were lost during follow-up irrespective of the Model for End-Stage Liver Disease (MELD) scores of the recipients in each category. Upon univariate analysis, grafts with moderate-to-severe steatosis (P = .012), those with severe liver preservation injury (P = .007) and prolonged cold ischemia time (P = .0001) showed a dismal prognosis at 1, 3, and 5 years. Upon multivariate analysis, fat content (P = .0076; OR = 4.2) and cold ischemia time >12 hours (P = .034; OR = 7.001) were independent predictors of graft survival. Among HCV recipients, marginal liver donors worked similar to those from "good" donors, except for those with fatty livers >30%, especially when combined with a prolonged cold ischemia time.     

Combined effects of fasting and alanine on liver function recovery after cold ischemia

The effect of donor nutritional status on hepatic function recovery after cold ischemia is still debated. We demonstrated previously that a 48-h fast diminished the survival rate of liver-transplanted rats and that the deleterious effect of fasting was prevented by infusion of alanine to the recipient at reperfusion. Whether the duration of fasting influenced the protective effect of alanine and whether this effect was metabolic were not known, and the elucidation of these questions is the aim of this study. The effect on hepatic function recovery of fasting periods of 24 h, 48 h and 72 h prior to cold ischemia were studied in a model of isolated, perfused rat liver. After a cold-ischemic time of 24 h in University of Wisconsin (UW) solution at 4 degrees C, livers were reperfused for 3 h. The combined effect of alanine (8 mM) infusion at liver reperfusion was evaluated for each prior fasting period. The addition of pyruvate (8 mM), a metabolic intermediary of alanine, was only tested in the 72-h fasting group. The evaluation criteria were: liver weight after reperfusion, release of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in the perfusate, bile production, vascular resistance and liver histology after reperfusion. The enzyme release at reperfusion was significantly higher when livers were harvested from rats submitted to a 48-h fast (ALT) or a 72-h fast (ALT, AST, LDH), as compared to those from fed rats. Vascular resistance was increased in 72-h fasted livers. An addition of alanine (8 mM) at reperfusion lowered the release of AST, ALT and LDH. This effect was more obvious when the fasting duration was increased. By contrast, the addition of pyruvate at reperfusion did not improve the recovery of livers submitted to a 72-h fasting period before preservation. A long fasting period is deleterious as compared to feeding; however, this effect can be compensated by infusion of alanine at reperfusion. The mechanism involved is not metabolic. In a clinical setting, the infusion of alanine to the recipient at reperfusion may be a convenient way to compensate for donor undernutrition, especially after a long stay in an intensive care unit.     

A simple scoring system to reduce intraabdominal septic complications after laparoscopic appendectomy

Background: The development of intraabdominal abscess (IAA) following laparoscopic appendectomy (LA) is associated with significant morbidity. The aim of the present study was to validate an IAA risk score constructed from a previous review of 156 consecutive LA. Methods: The score was tested in 250 subsequent consecutive LA and in patients with a positive risk score. Broad-spectrum antibiotics were administered in order to avoid IAA. Results: Factors related to IAA included clinically complicated appendicitis, leucocytosis >15,000/μl, a difference of >1°C between axillary and rectal temperature, intraoperative findings such as (gangrenes and perforation), and intraoperative perforation of the appendix. In this series, broad-spectrum antibiotic therapy in patients with a positive IAA risk score reduced the incidence of IAA from 7.05% to 1.60%. Conclusion: This policy of identifying high-risk patient via the scoring system and instituting subsequent antibiotic therapy in patients at risk reduces the incidence of IAA following LA. Received: 20 October 1999/Accepted: 7 March 2000/Online publication: 7 September 2000     

A simple scoring system to predict ambulation prognosis after hip fracture in the elderly

Introduction We conducted a study on elderly patients with hip fracture to examine whether it is possible to predict the ambulation status of these patients upon hospital discharge. Material and methods One hundred and eighty six patients with femoral neck or trochanteric fracture, who were ambulant prior to fracture, were studied. Thirteen factors that may affect walking ability were selected and subjected to multivariate analysis. Results Of 186 patients, 145 regained walking ability at discharge. Factors significantly affecting walking ability at discharge were (1) anemia, (2) dementia and (3) abnormal chest X-ray. Each patient was scored on the basis of the above factors (1 = yes, 0 = no), and the total was used as the predictive score. Conclusion A simple scoring system of the ambulation status upon hospital discharge. An erratum to this article can be found at     

A simple scoring system to estimate perioperative mortality following liver resection for primary liver malignancy—the Hepatectomy Risk Score (HeRS)

BackgroundSelection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections.MethodsThe 2005–2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7–10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1–4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values.ResultsA total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16–8.99), P=0.025; HeRS =3: OR =6.54 (2.39–17.90), P<0.001; HeRS =4: OR =13.69 (4.90–38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model.ConclusionsThe HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.