Prediction of survival after left-sided pancreatic resection for adenocarcinoma: Introduction of a new prognostic score.

BACKGROUND: Due to the clinically unapparent course the entity of left-sided pancreatic adenocarcinoma is often diagnosed at advanced stages, resulting in small numbers of patients qualifying for pancreatectomy. This study strives to develop a prognostic model for survival after left-sided pancreatic resection. METHODS: A total of 54 patients were analyzed. Pre- and intra-operative predictive factors for 18-month mortality were identified with multivariable binary logistic regression analysis and compiled into a prognostic model. The applicability was evaluated by assessment of the area under the receiver operating characteristic curve (AUROC). The model was internally validated applying a randomized backwards bootstrapping analysis. RESULTS: The 18-month mortality rate was 74.1% (n = 40). Mean survival was 19.1 months. A prognostic model for 18-month mortality after left sided-pancreatectomy showed an AUROC >0.800: 18-month mortality risk in% = Exp(Y) / (1 + Exp(Y)) with y= -0.927 + (1.724, if CA 19-9 elevated, otherwise 0) + (1.212 × number of intra-operative transfused packed red blood cells) + (2.771, if prior abdominal surgery, otherwise 0) - (3.612, if gastric resection, otherwise 0) This model was internally validated in 40 randomized backwards bootstrapping steps with AUROCs ranging from 0.757 to 0.971. CONCLUSIONS: The 18-month mortality risk for patients after left-sided pancreatectomy for adenocarcinoma of the pancreatic body can be assessed with the number of intra-operatively transfused packed red blood cells, elevated CA 19-9 levels, additional gastric resection and prior abdominal surgeries in the patient's history.

Potential savings in the treatment pathway of liver transplantation: an inter-sectorial analysis of cost-rising factors.

INTRODUCTION: Identification of cost-driving factors in patients undergoing liver transplantation is essential to target reallocation of resources and potential savings. AIM: The aim of this study is to identify main cost-driving factors in liver transplantation from the perspective of the Statutory Health Insurance. METHODS: Variables were analyzed with multivariable logistic regression to determine their influence on high cost cases (fourth quartile) in the outpatient, inpatient and rehabilitative healthcare sectors as well as for medications. RESULTS: Significant cost-driving factors for the inpatient sector of care were a high labMELD-score (OR 1.042), subsequent re-transplantations (OR 7.159) and patient mortality (OR 3.555). Expenditures for rehabilitative care were significantly higher in patients with a lower adjusted Charlson comorbidity index (OR 0.601). The indication of viral cirrhosis and hepatocellular carcinoma resulted in significantly higher costs for medications (OR 21.618 and 7.429). For all sectors of care and medications each waiting day had a significant impact on high treatment costs (OR 1.001). Overall, cost-driving factors resulted in higher median treatment costs of 211,435 €. CONCLUSIONS: Treatment costs in liver transplantation were significantly influenced by identified factors. Long pre-transplant waiting times that increase overall treatment costs need to be alleviated by a substantial increase in donor organs to enable transplantation with lower labMELD-scores. Disease management programs, the implementation of a case management for vulnerable patients, medication plans and patient tracking in a transplant registry may enable cost savings, e.g., by the avoidance of otherwise necessary re-transplants or incorrect medication.

Decision modelling for economic evaluation of liver transplantation.

As the gap between a shortage of organs and the immense demand for liver grafts persists, every available donor liver needs to be optimized for utility, urgency and equity. To overcome this challenge, decision modelling might allow us to gather evidence from previous studies as well as compare the costs and consequences of alternative options. For public health policy and clinical intervention assessment, it is a potentially powerful tool. The most commonly used types of decision analytical models include decision trees, the Markov model, microsimulation, discrete event simulation and the system dynamic model. Analytic models could support decision makers in the field of liver transplantation when facing specific problems by synthesizing evidence, comprising all relevant options, generalizing results to other contexts, extending the time horizon and exploring the uncertainty. For modeling studies of economic evaluation for transplantation, understanding the current nature of the disease is crucial, as well as the selection of appropriate modelling techniques. The quality and availability of data is another key element for the selection and development of decision analytical models. In addition, good practice guidelines should be complied, which is important for standardization and comparability between economic outputs.

Proposal of Two Prognostic Models for the Prediction of 10-Year Survival after Liver Resection for Colorectal Metastases.

BACKGROUND: One-third of 5-year survivors after liver resection for colorectal liver metastases (CLM) develop recurrence or tumor-related death. Therefore 10-year survival appears more adequate in defining permanent cure. The aim of this study was to develop prognostic models for the prediction of 10-year survival after liver resection for colorectal liver metastases. METHODS: N=965 cases of liver resection for CLM were retrospectively analyzed using univariable and multivariable regression analyses. Receiver operating curve analyses were used to assess the sensitivity and specificity of developed prognostic models and their potential clinical usefulness. RESULTS: The 10-year survival rate was 15.2%. Age at liver resection, application of chemotherapies of the primary tumor, preoperative Quick's value, hemoglobin level, and grading of the primary colorectal tumor were independent significant predictors for 10-year patient survival. The generated formula to predict 10-year survival based on these preoperative factors displayed an area under the receiver operating curve (AUROC) of 0.716. In regard to perioperative variables, the distance of resection margins and performance of right segmental liver resection were additional independent predictors for 10-year survival. The logit link formula generated with pre- and perioperative variables showed an AUROC of 0.761. CONCLUSION: Both prognostic models are potentially clinically useful (AUROCs >0.700) for the prediction of 10-year survival. External validation is required prior to the introduction of these models in clinical patient counselling.

Development and validation of a prognostic model for kidney function 1 year after combined pancreas and kidney transplantation using pre-transplant donor and recipient variables.

PURPOSE: The widening gap between demand and supply of organs for transplantation provides extraordinary challenges for ethical donor organ allocation rules. The transplant community is forced to define favorable recipient/donor combinations for simultaneous kidney-pancreas transplantation. The aim of this study is the development of a prognostic model for the prediction of kidney function 1 year after simultaneous pancreas and kidney transplantation using pre-transplant donor and recipient variables with subsequent internal and external validation. METHODS: Included were patients with end-stage renal failure due to diabetic nephropathy. Multivariable logistic regression modeling was applied for prognostic model design with retrospective data from Hannover Medical School, Germany (01.01.2000-31.12.2011) followed by prospective internal validation (01 Jan. 2012-31 Dec. 2015). Retrospective data from another German transplant center in Kiel was retrieved for external model validation via the initially derived logit link function. RESULTS: The developed prognostic model is able to predict kidney graft function 1 year after transplantation ≥ KDIGO stage III with high areas under the receiver operating characteristic curve in the development cohort (0.943) as well as the internal (0.807) and external validation cohorts (0.784). CONCLUSION: The proposed validated model is a valuable tool to optimize present allocation rules with the goal to prevent transplant futility. It might be used to support donor organ acceptance decisions for individual recipients.

Hangzhou criteria are more accurate than Milan criteria in predicting long-term survival after liver transplantation for HCC in Germany.

BACKGROUND: Milan criteria are used for patient selection in liver transplantation for hepatocellular carcinoma (HCC). Hangzhou criteria have been shown in China to enable access to liver transplantation for more patients when compared to Milan criteria without negative effects on long-term survival. The purpose of this study was to evaluate the Hangzhou criteria in a German cohort. METHODS: One hundred fifty-nine patients transplanted for HCC between 1975 and 2010 were investigated. Patients were categorized into four groups depending on the fulfillment of Milan and Hangzhou criteria. General and tumor baseline characteristics were compared. Overall and tumor-free survival rates were investigated with the Kaplan-Meier analysis. RESULTS: One-, 3-, 5-, and 10-year survival rates for patients fulfilling Milan criteria (n = 68) were 89.7, 83.7, 75.8, and 62.1%, respectively, versus 89.8, 82.2, 75.2, and 62.6% for patients fulfilling Hangzhou criteria (n = 109) (p = 0.833). When comparing patients exceeding Milan or Hangzhou criteria, survival rates were 75.3, 53.2, 48.1, and 41.1% versus 63.3, 31.4, 26.9, and 22.1%, respectively (p = 0.019). The comparison of tumor-free survival rates in patients fulfilling Milan or Hangzhou criteria was statistically not significant (p = 0.785), whereas the comparison of the groups exceeding the criteria showed significantly worse survival for patients outside Hangzhou criteria (p = 0.007). The proportion of patients fulfilling Hangzhou criteria (68.6%) was significantly larger as compared to the proportion fulfilling Milan criteria (42.8%) (p < 0.001). CONCLUSION: Hangzhou criteria are more accurate in predicting long-term survival after liver transplantation for HCC in Germany. Deployment of the Hangzhou criteria for patient selection could enlarge the pool of transplantable patients.

Relevant prognostic factors influencing outcome of patients after surgical resection of distal cholangiocarcinoma.

BACKGROUND: Distal cholangiocarcinoma (DCC) is a rare but over the last decade increasing malignancy and is associated with poor prognosis. According to the present knowledge curative surgery is the only chance for long term survival. This study was performed to evaluate prognostic factors for the outcome of patients undergoing curative surgery for distal cholangiocarcinoma. METHODS: 75 patients who underwent surgery between January 2000 and December 2014 for DCC in curative intention were analysed retrospectively. Potential prognostic factors for survival were investigated including the extent of surgery using purposeful selection of covariates in multivariable Cox regression modeling. RESULTS: Preoperative biliary stenting (Hazard ratio (HR): 2.530; 95%-CI: 1.146-6.464, p = 0.020), the extent of surgery in case of positive histological venous invasion (HR: 1.209; 95%-CI: 1.017-1.410, p = 0.032), lymph node staging (HR: 2.183; 95%-CI: 1.250-3.841, p = 0.006), perineural invasion (HR: 2.118; 95%-CI: 1.147-4.054, p = 0.016) and postoperative complications graded in points according to Clavien-Dindo (HR: 1.395; 95%-CI: 1.148-1.699, p = 0.001) were indentified as independent significant risk factors for survival. Patients receiving preoperative biliary stenting showed prolonged duration between onset of symptoms and date of operation (p = 0.048). CONCLUSIONS: Preoperative biliary stenting reduces survival possibly due to delayed surgery. The extent of surgery is not an independent risk factor for survival except for patients with concomitant histological venous invasion. Oncological factors and postoperative surgical complications are independent prognostic factors for survival.

Evaluation of published assessment tools for comorbidity in liver transplantation: a systematic review protocol.

INTRODUCTION: Liver transplantation is considered the best therapy option for end-stage liver disease. Different factors including recipient comorbidity at time of transplantation are supposed to have substantial impact on outcomes. Although several studies have focused on comorbidity assessment indices for liver transplant recipients, there is no systematic review available on the methodological details and prognostic accuracy of these instruments. The aim of this study is to systematically review recipient comorbidity assessment indices in the context of liver transplantation. METHODS AND ANALYSIS: PubMed, Embase, Web of Science and PsyINFO databases will be searched. Studies describing, using or evaluating specific assessment tools to predict the effect of comorbidity on clinical outcomes after liver transplantation will be included. The selection will be conducted independently by two reviewers. The study characteristics and methodological information on published comorbidity assessment tools will be extracted into a predefined structural table. This approach will be deployed to systematically extract information on the validity, reliability and practical feasibility of investigated comorbidity assessment tools for comparative evaluation. Narrative information synthesis will be conducted, and additional meta-analytical comparison will be performed, if appropriate. ETHICS AND DISSEMINATION: All data are collected from published literature. Thus, formal ethics review for the research is not required. The findings of this systematic review will be published in a peer-reviewed journal and presented at relevant conferences. The results of this systematic review will be highly relevant for further research on prognostic models, clinical decision making and optimisation of donor organ allocation. PROSPERO REGISTRATION NUMBER: CRD42017074609.

Prognostic factors for long-term survival after adult liver transplantation.

PURPOSE: Prognostic factors for survival ≥ 15 years and life years lost after liver transplantation are largely unknown. METHODS: One thousand six hundred thirty primary adult liver transplants between 1983 and 2014 were analyzed. Risk factors for survival were identified with multivariable Cox regression and subsequently tested for their relevance as prognostic factors for observed 15-year survival using multivariable logistic regression and c statistics. The difference of life expectancy between a matched national reference population and survival in patients with post-transplant survival ≥ 15 years was calculated. RESULTS: Survival of ≥ 15 years was observed in 361 patients (22%). Sixty-nine adults died after more than 15 years losing a median of 15 years of life expectancy. One of those patients lived longer while 292 patients still have the chance to survive longer than their normal life expectancy. The indication primary sclerosing cholangitis (PSC) and later eras of transplantation were identified as significant independent protective factors while recipient age > 36.8 years, graft loss due to initial non-function or thrombosis, the indications hepatocellular carcinoma (HCC), hepatitis-C-virus-related cirrhosis (HCV-cirrhosis) and all other indications, donor age > 53 years, the number of surgical complications, and operative durations > 4.5 h were identified as significant independent risk factors limiting survival. All of these factors except the duration of operation had also a significant independent influence on observed 15-year survival (AUROC = 0.739). CONCLUSIONS: Recipients can exceptionally live longer than their normal life expectancy. Older recipients and patients with the indications HCC, HCV-cirrhosis, or other indications except PSC, should be transplanted with younger donor organs.

Statistical approach to quality assessment in liver transplantation.

PURPOSE: This study investigated the utility of retrospective two one-sided cumulative sum (CUSUM) charts combined with multivariable regression analysis in liver transplantation for transplant center benchmarking. METHODS: One thousand seven hundred and forty-nine consecutive adult primary liver transplants (January 1, 1983 to December 31, 2012) were analyzed retrospectively with two one-sided CUSUM chart analysis of 90-day mortality. RESULTS: Three eras and two subseries in latest era 3 were identified due to graphically delineated relevant shifts in mean 90-day mortality. Delineation of eras 1, 2, and 3 coincided with relevant changes in allocation policies. CUSUM analysis detected a resurgence of higher mean 90-day mortality in era 3 after results had improved continuously over 25 years. In era 3, two subseries were identified with improving mean 90-day mortality rates from 15.4% in subseries 1 to 8.9% in the following subseries 2. The quantitative influence of independent risk factors on 90-day mortality differed markedly between all identified eras and subseries as assessed with multivariable regression analysis deployed on era-specific subcohorts. CONCLUSION: The assessed methodology is able to identify meaningful center-specific eras and subseries of liver transplantation with striking alterations of the significance and weight of outcome drivers for post-transplant 90-day mortality over time. This warrants the introduction of prospective risk-adjusted two one-sided CUSUM chart analysis into quality management in liver transplantation in Germany with the goal to obtain alarm signals as early as possible.

Timing of parathyroidectomy in kidney transplant candidates with secondary hyperparathryroidism: effect of pretransplant versus early or late post-transplant parathyroidectomy.

BACKGROUND: The timing of parathyroidectomy in kidney transplant candidates suffering from secondary hyperparathyroidism before versus early or late after transplantation remains controversial. METHODS: The short-term follow-up cohort comprised 66 patients with 1-year post-transplant follow-up, while the long-term follow-up cohort contained 123 patients. Risk-adjusted identification of independent risk factors for compromised renal graft function (KDIGO stage ≥ IV) was performed using multivariable regression analysis adjusted for propensity score logits for parathyroidectomy before versus after renal transplantation. Intra-individual matched-pairs analyses were used to identify significant effects of post-transplant parathyroidectomy on graft function as assessed by estimated glomerular filtration rate (eGFR) and paired t tests. RESULTS: Donor kidney function KDIGO stage III (P = .030; OR = 5.191, 95% CI: 1.100-24.508), donor blood group 0 (P = .005; OR = 0.176, 95% CI: 0.048-0.642), and post-transplant parathyroidectomy (P = .032; OR = 17.849, 95% CI: 1.086-293.268) were revealed as independent significant risk factors for compromised renal graft function in the short-term follow-up cohort using propensity score risk adjustment while post-transplant parathyroidectomy had no independent influence in the long-term follow-up cohort (P = .651). Parathyroidectomy after renal transplantation compromised graft function early after parathyroidectomy and at last follow-up in all post-transplant parathyroidectomy cases (P ≤ .004). Parathyroidectomy within the first post-transplant year was associated with compromised renal graft function until last follow-up (P = .004), while parathyroidectomy late post-transplant was not. CONCLUSION: Parathyroidectomy should be conducted before transplantation or, if this is not possible, preferably after the first post-transplant year.

Introduction of the resection severity index as independent risk factor limiting survival after resection of colorectal liver metastases.

BACKGROUND: The purpose of this study is to evaluate the influence of the recently introduced resection severity index (RSI) in patients with liver resection for hepatocellular carcinoma on survival after resection of colorectal liver metastases. The RSI quantifies pre-operatively the liver cellular damage, liver synthetic function and loss of organ parenchyma. METHODS: All consecutive patients who underwent liver resection for metastases of colorectal cancer (CLM) between 2000 and 2015 were included in this study. Risk factors limiting survival were analyzed using univariable and multivariable Cox regression analyses. RESULTS: The median survival after liver resection for CLM was 3.0 years. Significant independent risk factors for mortality were the RSI (p = 0.029; hazard ratio (HR): 1.088, 95%-confidence interval (95%-CI): 1.009-1.174), age at resection in years (p = 0.001; HR: 1.017, 95%-CI: 1.007-1.027), pre-operative hemoglobin level (p = 0.041; HR: 0.932, 95%-CI: 0.891-0.997), the cecum as location of primary CRC (p < 0.001; HR: 2.023, 95%-CI: 1.403-2.833), adjuvant chemotherapy (p < 0.001; HR: 1.506, 95%-CI: 1.212-1.878), local relapse of the primary tumor (p = 0.027; HR: 1.591, 95%-CI: 1.057-2.297), the units of intra-operatively transfused packed red blood cells (p < 0.001; HR: 1.068, 95%-CI: 1.033-1.104), the size of the largest metastasis (p = 0.002; HR: 1.005, 95%-CI: 1.002-1.008) and the metastasis' distance to the resection margin (p = 0.014; HR: 0.984, 95%-CI: 0.972-0.997). CONCLUSION: The RSI is an independent prognostic factor for survival after liver resection for CLM. Besides the extent of liver resection certain primary tumor characteristics have to be taken into account to ensure long-term survival.

Risk-factors for nodular hyperplasia of parathyroid glands in sHPT patients.

INTRODUCTION: Nodular hyperplasia of parathyroid glands (PG) is the most probable cause of medical treatment failure in secondary hyperparathyroidism (sHPT). This prospective cohort study is located at the interface of medical and surgical consideration of sHPT treatment options and identifies risk-factors for nodular hyperplasia of PG. MATERIAL AND METHODS: One-hundred-eight resected PG of 27 patients with a broad spectrum of sHPT severity were classified according to the degree of hyperplasia by histopathology. Twenty routinely gathered parameters from medical history, ultrasound findings of PG and laboratory results were analyzed for their influence on nodular hyperplasia of PG by risk-adjusted multivariable binary regression. A prognostic model for non-invasive assessment of PG was developed and used to weight the individual impact of identified risk-factors on the probability of nodular hyperplasia of single PG. RESULTS: Independent risk-factors for nodular hyperplasia of single PG were duration of dialysis in years, PG volume in mm3 determined by ultrasound and serum level of parathyroid hormone in pg/mL. Multivariable analyses computed a model with an Area Under the Receiver Operative Curve of 0.857 (95%-CI:0.773-0.941) when predicting nodular hyperplasia of PG. Theoretical assessment of risk-factor interaction revealed that the duration of dialysis had the strongest influence on the probability of nodular hyperplasia of single PG. CONCLUSIONS: The three identified risk-factors (duration of dialysis, PG volume determined by ultrasound and serum level of parathyroid hormone) can be easily gathered in daily routine and could be used to non-invasively assess the probability of nodular hyperplasia of PG. This assessment would benefit from periodically collected data sets of PG changes during the course of sHPT, so that the choice of medical or surgical sHPT treatment could be adjusted more to the naturally changing type of histological PG lesion on an individually adopted basis in the future.

External validation of a proposed prognostic model for the prediction of 1-year postoperative eGFR after living donor nephrectomy.

PURPOSE: The goal of this study was to externally validate the recently proposed prognostic model for the prediction of estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 1 year after living donor nephrectomy. METHODS: 130 living kidney donors (median age at donation 52.3 years, range 24.7-75.6 years) were investigated before and after donation between March 2000 and April 2016. Preoperative eGFR values varied between 61.7 and 148.4 ml/min (mean: 89, median: 88). Observed eGFR 1 year after transplantation (±45 days) ranged between 36.3 and 97.1 ml/min (mean: 55, median: 53). 70.8% of donors displayed eGFR values < 60 ml/min 1 year after donation. Predicted eGFR 1 year after donation was determined using the prognostic model proposed by Benoit et al. (Int Urol Nephrol 49(5):793-801. doi: 10.1007/s11255-017-1559-1 , 2017): postoperative eGFR ml/min/1.73 m2 = 31.71 + (0.521 × eGFR in ml/min prior to donation -0.314 × Age in years at donation). Pearson correlation and receiver operating characteristics curve (ROC-curve) were used to assess external validity of the proposed prognostic model to predict postoperative eGFR in ml/min and eGFR < 60 ml/min. RESULTS: The correlation between predicted and observed eGFR 1 year after donation was significant (p < 0.001; R 2 = 0.594). The area under the ROC-curve (AUROC) demonstrated a high sensitivity and specificity for predicted eGFR values < 60 ml/min (AUROC = 0.866). CONCLUSIONS: The proposed prognostic model for the prediction of postoperative eGFR was successfully validated in our cohort. We therefore consider the model as generally applicable.

Identifying independent risk factors for graft loss after primary liver transplantation.

PURPOSE: The aim of the study is the identification of independent risk factors for re-transplantation after primary liver transplantation beyond the occurrence of hepatic artery thrombosis. METHODS: Eight hundred thirty-four adult patients undergoing primary liver transplantation were analyzed. A propensity score was developed using multivariable binary logistic regression with hepatic artery thrombosis as the dependent variable. The logit link function of the propensity score was included into multivariable Cox regression analysis for graft survival to adjust the study population. RESULTS: Graft loss was observed in 134 patients (16.1%). Independent significant risk factors for graft loss were recipient platelet count (p = 0.040; HR: 1.002; 95%-CI: 1.000-1.003), preoperative portal vein thrombosis (p = 0.032; HR: 1.797; 95%-CI: 1.054-2.925), donor age (p < 0.001; HR: 1.026; 95%-CI: 1.012-1.040), percentage of macrovesicular steatosis of the graft (p = 0.011; HR: 1.037; 95%-CI: 1.009-1.061), early complications leading to revision surgery (p < 0.001; HR: 2.734; 95%-CI: 1.897-3.956), duration of the transplant procedure (p < 0.001; HR: 1.005; 95%-CI: 1.003-1.007) as well as transplantation of a split liver graft (p = 0.003; HR: 2.637; 95%-CI: 1.420-4.728). The logit of the propensity score did not reach statistical significance in the final multivariable Cox regression model (p = 0.111) indicating good adjustment for the occurrence of hepatic artery thrombosis. CONCLUSION: Liver transplant programs might benefit from regular donor organ biopsies to assess the amount of macrovesicular steatosis. An elevated recipient platelet count can promote reperfusion injury leading to graft loss. A liver graft from an elderly donor should not be split or be transplanted in a recipient with detected portal vein thrombosis.

Identification of the resection severity index as a significant independent prognostic factor for early mortality and observed survival >5 and >10 years after liver resection for hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: This study evaluates predictive factors for observed long-term survival of more than 5 and 10 years for patients after liver resection for hepatocellular carcinoma and compares their life expectancy to the normal national population matched for sex, year of birth and age at resection. METHODS: 230 patients after primary liver resection for HCC (01.01.1995-31.12.2004) were analyzed. Multivariable logistic regression models were determined based on Cox regression results and their prognostic capability evaluated with areas under the receiver operating characteristic curve (AUROCs). RESULTS: Life years after surgery in deceased patients compared to the normal national population matched for sex, year of birth and age at resection was reduced by median 21.7 years. Independent predictive factors for 10-year survival were age at resection (p < 0.001; OR = 0.898; 95%-CI: 0.846-0.954), UICC 7 tumor staging (p = 0.003; OR = 0.344; 95%-CI: 0.126-0.941) and ASAT (GOT) in U/l divided by Quick in percent multiplied by the extent of liver resection graded in points labelled as the resection severity index (p < 0.001; OR = 0.136; 95%-CI: 0.022-0.843) enabling prediction of 10-year survival with an AUROC of 0.884. The same factors plus revision surgery (yes/no) predict 5-year survival (AUROC 0.736). CONCLUSIONS: Liver resection enables predictable long-term survival >5 and > 10 years. The proposed resection severity index quantifies the prognostic relevance of liver cellular damage, synthesis and loss of parenchyma for long-term survival.

Biliary complications following liver transplantation: Single-center experience over three decades and recent risk factors.

AIM: To identify independent risk factors for biliary complications in a center with three decades of experience in liver transplantation. METHODS: A total of 1607 consecutive liver transplantations were analyzed in a retrospective study. Detailed subset analysis was performed in 417 patients, which have been transplanted since the introduction of Model of End-Stage Liver Disease (MELD)-based liver allocation. Risk factors for the onset of anastomotic biliary complications were identified with multivariable binary logistic regression analyses. The identified risk factors in regression analyses were compiled into a prognostic model. The applicability was evaluated with receiver operating characteristic curve analyses. Furthermore, Kaplan-Meier analyses with the log rank test were applied where appropriate. RESULTS: Biliary complications were observed in 227 cases (14.1%). Four hundred and seventeen (26%) transplantations were performed after the introduction of MELD-based donor organ allocation. Since then, 21% (n = 89) of the patients suffered from biliary complications, which are further categorized into anastomotic bile leaks [46% (n = 41)], anastomotic strictures [25% (n = 22)], cholangitis [8% (n = 7)] and non-anastomotic strictures [3% (n = 3)]. The remaining 18% (n = 16) were not further classified. After adjustment for all univariably significant variables, the recipient MELD-score at transplantation (P = 0.006; OR = 1.035; 95%CI: 1.010-1.060), the development of hepatic artery thrombosis post-operatively (P = 0.019; OR = 3.543; 95%CI: 1.233-10.178), as well as the donor creatinine prior to explantation (P = 0.010; OR = 1.003; 95%CI: 1.001-1.006) were revealed as independent risk factors for biliary complications. The compilation of these identified risk factors into a prognostic model was shown to have good prognostic abilities in the investigated cohort with an area under the receiver operating curve of 0.702. CONCLUSION: The parallel occurrence of high recipient MELD and impaired donor kidney function should be avoided. Risk is especially increased when post-transplant hepatic artery thrombosis occurs.

Ultrasound-based scores as predictors for nodular hyperplasia in patients with secondary hyperparathyroidism: a prospective validation study.

PURPOSE: Former studies evaluated echostructural and vascular patterns in ultrasound of the parathyroid gland to identify nodular hyperplasia in patients with secondary hyperparathyroidism due to chronic kidney disease. This prospective study aims to externally validate suggested ultrasound classifications. METHODS: Parathyroid glands of 27 patients with secondary hyperparathyroidism undergoing parathyroidectomy were prospectively analyzed. Ultrasound including Doppler imaging was performed 1 day prior to surgery. Ultrasound data were available for 70 parathyroid glands. Echostructural and vascular scores according to previous studies were applied calculating the area under the receiver operating characteristic curve (AUROC). Overall correctness, sensitivity, and specificity of the investigated scores were assessed with the Youden index method. RESULTS: The Doppler score introduced by Vulpio and colleagues based on characteristic blood flow patterns in parathyroid glands showed an AUROC of 0.749 for the prediction of nodular hyperplasia with an overall correctness of 72.8%. Other ultrasound classifications based on blood flow patterns, as well as echostructure of the parathyroid gland displayed AUROCs of <0.700, thus, lacking sufficient capability as a prognostic model. Overall correctness of prediction varied from 53.8 to 55.9%. CONCLUSIONS: The Vulpio Doppler score for the prediction of nodular hyperplasia in patients with secondary hyperparathyroidism was externally validated for the first time. Other ultrasound scores fail as prognostic models in this study population. Doppler sonography of the parathyroid gland has prognostic capability to identify nodular hyperplasia as surrogate marker for patients with secondary hyperparathyroidism indicating the need for ablative or surgical treatment when failing conservative therapy.

Comparable outcome of liver transplantation with histidine-tryptophan-ketoglutarate vs. University of Wisconsin preservation solution: a retrospective observational double-center trial.

BACKGROUND: The question of whether the choice of preservation solution affects outcome after liver transplantation is still not satisfactorily answered. The purpose of this study is to examine the preservation solutions' impact on outcome after liver transplantation. METHODS: A double-center retrospective study of short- and long-term results of 3134 consecutive liver transplantations with follow-up periods up to 23 years was performed applying multivariate, risk-adjusted analyses with a subset for living-donor transplants, pediatric transplants and cases with prolonged cold ischemic times. An additional focus was put on biliary complications. The primary study endpoints were short- and long-term patient survival and death-censored graft survival. Secondary study endpoints were the occurrence of post-transplant complications, the necessity of operative revisions, the length of hospital stay, and the length of intensive care unit stay. RESULTS: Although long-term graft survival appears to be increased by Histidine-Tryptophan-Ketoglutarate-use (p = 0.018), this effect could not be confirmed in risk-adjusted analysis (p = 0.641). Multivariate regression analysis revealed that 3-month mortality (p = 0.120), 3-month graft survival (p = 0.103) and long-term patient survival (p = 0.235) were not influenced by the choice of preservation solution. There was no difference in the occurrence of common complications or necessity of operative revisions after liver transplantation. This was confirmed in subgroup analyses for living donor and pediatric transplantation and cases with prolonged cold ischemic time. Analysis of the preservation solutions' impact on length of hospital (p = 0.113) and intensive care unit stay (p = 0.481) revealed no significant difference. CONCLUSIONS: University of Wisconsin and Histidine-Tryptophan-Ketoglutarate solutions are clinically equivalent. Histidine-Tryptophan-Ketoglutarate solution could have an economically superior profile. The notion that the choice of preservation solution can have an impact on the onset of biliary complications after liver transplantation remains a matter of controversy.