Impact of cumulative complications on 1-year treatment-related healthcare costs in patients with colorectal peritoneal metastases undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The aim of this study was to evaluate the impact of all minor and major complications on treatment-related healthcare costs in patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal metastases (PMs). METHOD: Patients with histologically proven colorectal PMs who underwent CRS + HIPEC from March 2006 to October 2019 in a tertiary referral centre were retrospectively identified from a prospectively maintained database. Patients were divided into six subgroups according to the severity of the complications, which were scored using the comprehensive complication index (CCI) (CCI 0-9.9, CCI 10-19.9, CCI 20-29.9, CCI 30-39.9, CCI 40-49.9, and CCI 50 or higher). Treatment-related healthcare costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the chi-squared test and Kruskal-Wallis H test. RESULTS: A total of 142 patients were included (CCI 0-9.9, 53 patients; CCI 10-19.9, 0 patients; CCI 20-29.9, 45 patients; CCI 30-39.9, 14 patients; CCI 40-49, 9 patients; and CCI 50 or higher, 21 patients). Median (interquartile range) treatment-related healthcare costs increased significantly and exponentially for the CCI 30-39, CCI 40-49, and CCI 50 or higher groups (€48 993 (€44 262-€84 805); €57 167 (€43 047-€67 591); and €82 219 (€55 487-€145 314) respectively) compared with those for the CCI 0-9.9 and CCI 20-29.9 groups (€33 856 (€24 433-€40 779) and €40 621 (€31 501-€58 761) respectively, P < 0.010). CONCLUSION: Treatment-related healthcare costs increase exponentially as more complications develop among patients who undergo CRS + HIPEC for the treatment of colorectal PMs. Anastomotic leakages after CRS + HIPEC lead to an increase of 295 per cent of treatment-related healthcare costs.

The Costs of Complications and Unplanned Readmissions after Pancreatoduodenectomy for Pancreatic and Periampullary Tumors: Results from a Single Academic Center.

BACKGROUND/OBJECTIVES: Complications after pancreatoduodenectomy (PD) lead to unplanned readmissions (UR), with a two- to threefold increase in admission costs. In this study, we aimed to create an understanding of the costs of complications and UR in this patient group. Furthermore, we aimed to generate a detailed cost overview that can be used to build a theoretical model to calculate the cost efficacy for prehabilitation. METHODS: A retrospective cohort analysis was performed using the Dutch Pancreatic Cancer Audit (DPCA) database of patients who underwent a PD at our institute between 2013 and 2017. The total costs of the index hospital admission and UR related to the PD were collected. RESULTS: Of the 160 patients; 35 patients (22%) had an uncomplicated course; 87 patients (54%) had minor complications, and 38 patients (24%) had severe complications. Median costs for an uncomplicated course were EUR 25.682, and for a complicated course, EUR 32.958 (p = 0.001). The median costs for minor complications were EUR 30.316, and for major complications, EUR 42.664 (p = 0.001). Costs were related to the Comprehensive Complication Index (CCI). The median costs of patients with one or more UR were EUR 41.199. CONCLUSIONS: Complications after PD led to a EUR 4.634-EUR 16.982 (18-66%) increase in hospital costs. A UR led to a cost increase of EUR 12.567 (44%). Since hospital costs are directly related to the CCI, reduction in complications will lead to cost-effectiveness.

Does the meld system provide equal access to liver transplantation for patients with different ABO blood groups?

This study investigates the relationship between blood group and waiting time until transplantation or death on the waiting list. All patients listed for liver transplantation in the Netherlands between 15 December 2006 and 31 December 2012, were included. Study variables were gender, age, year of listing, diagnosis, previous transplantations, blood group, urgency, and MELD score. Using a competing risks analysis, separate cumulative incidence curves were constructed for death on the waiting list and transplantation and used to evaluate outcomes.In 517 listings, the mean death rate per 100 patient-years was 10.4. A total of 375 (72.5% of all listings) were transplanted. Of all transplantations, 352 (93.9%) were ABO-identical and 23 (6.1%) ABO-compatible. The 5-year cumulative incidence of death was 11.2% (SE 1.4%), and of transplantation 72.5% (SE 2.0%). Patient blood group had no multivariate significant impact on the hazard of dying on the waiting list nor on transplantation. Age, MELD score, and urgency status were significantly related to the death on the waiting list and transplantation. More recent listing had higher probability of being transplanted. In the MELD era, patient blood group status does not have a significant impact on liver transplant waiting list mortality nor on waiting time for transplantation.

The price of donation after cardiac death in liver transplantation: a prospective cost-effectiveness study.

This study aims to perform a detailed prospective observational multicenter cost-effectiveness study by comparing liver transplantations with donation after brain death (DBD) and donation after cardiac death (DCD) grafts. All liver transplantations in the three Dutch liver transplant centers between 2004 and 2009 were included with 1-year follow-up. Primary outcome parameter was cost per life year after transplantation. Secondary outcome parameters were 1-year patient and graft survival, complications, and patient-level costs. From 382 recipients that underwent 423 liver transplantations, 293 were primarily transplanted with DBD and 89 with DCD organs. Baseline characteristics were not different between both groups. The Donor Risk Index was significantly different as were cold and warm ischemic time. Ward stay was significantly longer in DCD transplantations. Patient and graft survival were not significantly different. Patients receiving DCD organs had more and more severe complications. The cost per life year for DBD was € 88,913 compared to € 112,376 for DCD. This difference was statistically significant. DCD livers have more and more severe complications, more reinterventions and consequently higher costs than DBD livers. However, patient and graft survival was not different in this study. Reimbursement should be differentiated to better accommodate DCD transplantations.

Implantable continuous Doppler monitoring device for detection of hepatic artery thrombosis after liver transplantation.

BACKGROUND: Early hepatic artery thrombosis (eHAT) after liver transplantation occurs in 3% of adults and 8% of children and often results in retransplantation. eHAT is initially asymptomatic and arterial patency is monitored with percutaneous Doppler ultrasound screening (pDUS). The aim of the study is to analyze the diagnostic accuracy of "continuous" Doppler registration (CONDOR) using an implantable miniature Doppler. METHODS: This prospective observational study was conducted in 102 liver transplant recipients. Hepatic arterial signal is checked by CONDOR at least six times per day for the first 10 days after transplantation with comparison of diagnostic accuracy of CONDOR versus pDUS. RESULTS: Extra investigations were performed after 48 (11%) regular pDUS where arterial patency was questioned: 32 extra pDUS, 14 computed tomography (CT) angiographies, and 2 reoperations. CT scan confirmed eHAT in 4 cases. In 10 cases of pDUS-suspected eHAT, where subsequent CT showed an open artery, the CONDOR signal was clearly pulsatile. In 2 of 4 patients with five eHATs, a weak arterial signal was inadvertently interpreted as an open artery (sensitivity of 60%). The accuracy for detection of eHAT increased from 93% (pDUS) to 99% (CONDOR). Using CONDOR, additional CT angiographies may be prevented in 10% of cases. CONCLUSION: CONDOR is a useful adjunct to pDUS because it reduces the false-positive rate of pDUS. Further development of the technique and analysis of the signal generated by CONDOR are needed to improve the sensitivity before CONDOR can replace pDUS as a reliable screening method for detection of eHAT.

The clinical relevance of the anhepatic phase during liver transplantation.

This study assesses the relation between the anhepatic phase duration and the outcome after liver transplantation. Of 645 patients who underwent transplantation between 1994 and 2006, 194 were recipients of consecutive adult primary piggyback liver transplants using heart-beating donors. The anhepatic phase was defined as the time from the physical removal of the liver from the recipient to recirculation of the graft. Other noted study variables were the cold and warm ischemia times, donor and recipient age, donor and recipient body mass index, perioperative red blood cell (RBC) transfusion, indication for transplantation, and Model for End-Stage Liver Disease score. The primary outcome parameter was graft dysfunction, which was defined as either primary nonfunction or initial poor function according to the Ploeg-Maring criteria. The median anhepatic phase was 71 minutes (37-321 minutes). Graft dysfunction occurred in 27 patients (14%). Logistic regression analysis showed an anhepatic phase over 100 minutes [odds ratio (OR), 4.28], a recipient body mass index over 25 kg/m(2) (OR, 3.21), and perioperative RBC transfusion (OR, 3.04) to be independently significant predictive factors for graft dysfunction. One-year patient survival in patients with graft dysfunction was 67% versus 92% in patients without graft dysfunction (P < 0.001). A direct relation between the anhepatic phase duration and patient survival could, however, not be established. In conclusion, this study shows that liver transplant patients with an anhepatic phase over 100 minutes have a higher incidence of graft dysfunction. Patients with graft dysfunction have significantly worse 1-year patient survival.

Is Roux-en-Y choledochojejunostomy an independent risk factor for nonanastomotic biliary strictures after liver transplantation?

Biliary reconstruction using Roux-en-Y choledochojejunostomy has been suggested as a risk factor for the development of nonanastomotic biliary strictures (NAS) after liver transplantation. Roux-en-Y reconstruction, however, is preferentially used in patients transplanted for primary sclerosing cholangitis (PSC), and the disease itself is also associated with a higher incidence of NAS. The aim of this study was to determine whether Roux-en-Y reconstruction is really an independent risk factor for NAS. A series of 486 consecutive adult liver transplants were studied. Biliary reconstruction in patients transplanted for PSC was either by Roux-en-Y choledochojejunostomy or by duct-to-duct anastomosis, depending on the quality of the recipient's extrahepatic bile duct. Univariate and multivariate statistical analyses were used to identify risk factors for the development of NAS. The overall incidence of NAS was 16.5% (80/486). In univariate analyses, the following variables were significantly associated with NAS: PSC as the indication for transplantation, type of biliary reconstruction (Roux-en-Y versus duct-to-duct), and postoperative cytomegalovirus infection. After multivariate logistic regression analysis, PSC as the indication for transplantation (odds ratio, 2.813; 95% confidence interval, 1.624-4.875; P < 0.001) and postoperative cytomegalovirus infection (odds ratio, 2.098; 95% confidence interval, 1.266-3.477; P = 0.004) remained as independent risk factors for NAS. Biliary reconstruction using Roux-en-Y choledochojejunostomy was not identified as an independent risk factor for NAS. In conclusion, the association between Roux-en-Y choledochojejunostomy and NAS observed in previous studies can be explained by the more frequent use of Roux-en-Y reconstruction in patients with PSC. Roux-en-Y reconstruction itself is not an independent risk factor for NAS. Liver Transpl 15:924-930, 2009. (c) 2009 AASLD.

Cost of liver transplantation: a systematic review and meta-analysis comparing the United States with other OECD countries.

Large cost variations of liver transplantation are reported. The aim of this study was to assess cost differences of liver transplantation and clinical follow-up between the United States and other Organization for Economic Cooperation and Development (OECD) countries. Eight electronic databases were searched, and 2,000 citations published after 1990 with more than 10 transplantations, and with original cost data, were identified. A total of 30 articles included 5,975 liver transplantations. Meta-analysis was used to derive a combined mean using a random-effects model to test for heterogeneity between studies. Estimated mean cost of a U.S. liver transplantation was US$163,438 (US$145,277-181,598) compared to US$103,548 (US$85,514-121,582) for other OECD countries. Patient characteristics, disease characteristics, quality of the health care provider, and methodology could not explain this cost difference. Health system characteristics differed between the U.S. and other OECD countries. Cost differences in liver transplantation between these two groups may be largely explained by health system characteristics.

The survival paradox of elderly patients after major liver resections.

OBJECTIVE: The objective of this study is to assess the outcome of liver resections in the elderly in a matched control analysis. PATIENTS AND METHODS: From a prospective single center database of 628 patients, 132 patients were aged 60 years or over and underwent a primary major liver resection. Of these patients, 93 could be matched one-to-one with a control patient, aged less than 60 years, with the same diagnosis and the same type of liver resection. The mean age difference was 16.7 years. RESULTS: Patients over 60 years of age had a significantly higher American Society of Anaesthesiologists (ASA) grade. All other demographics and operative characteristics were not different. In-hospital mortality and morbidity were higher in the patients over 60 years of age (11% versus 2%, p = 0.017 and 47% versus 31%, p = 0.024). One-, 3-, and 5-year survival rates in the patients over 60 years of age were 81%, 58%, and 42%, respectively, compared to 90%, 59%, and 42% in the control patients (p = 0.558). Unified model Cox regression analysis showed that resection margin status (hazard ratio 2.51) and ASA grade (hazard ratio 2.26), and not age, were determining factors for survival. CONCLUSION: This finding underlines the important fact that in patient selection for major liver resections, ASA grade is more important than patient age.

The impact of intraoperative transfusion of platelets and red blood cells on survival after liver transplantation.

BACKGROUND: Intraoperative transfusion of red blood cells (RBC) is associated with adverse outcome after orthotopic liver transplantation (OLT). Although experimental studies have shown that platelets contribute to reperfusion injury of the liver, the influence of allogeneic platelet transfusion on outcome has not been studied in detail. In this study, we evaluate the impact of various blood products on outcome after OLT. METHODS: Twenty-nine variables, including blood product transfusions, were studied in relation to outcome in 433 adult patients undergoing a first OLT between 1989 and 2004. Data were analyzed using uni- and multivariate stepwise Cox's proportional hazards analyses, as well as propensity score-adjusted analyses for platelet transfusion to control for selection bias in the use of blood products. RESULTS: The proportion of patients receiving transfusion of any blood component decreased from 100% in the period 1989-1996 to 74% in the period 1997-2004. In uni- and multivariate analyses, the indication for transplantation, transfusion of platelets and RBC were highly dominant in predicting 1-yr patient survival. These risk factors were independent from well-accepted indices of disease, such as the Model for End-Stage Liver Disease score and Karnofsky score. The effect on 1-yr survival was dose-related with a hazard ratio of 1.377 per unit of platelets (P = 0.01) and 1.057 per unit of RBC (P = 0.001). The negative impact of platelet transfusion on survival was confirmed by propensity-adjusted analysis. CONCLUSION: This retrospective study indicates that, in addition to RBC, platelet transfusions are an independent risk factor for survival after OLT. These findings have important implications for transfusion practice in liver transplant recipients.

Emergency abdominal aortic aneurysm repair with a preferential endovascular strategy: mortality and cost-effectiveness analysis.

PURPOSE: To assess mortality and treatment costs of a new management protocol with preferential use of emergency endovascular aneurysm repair (eEVAR) for acute abdominal aortic aneurysm (AAA). METHODS: From September 2003 until February 2005, 49 consecutive patients (45 men; mean age 71 years) with acute AAA were entered into a prospective study of a new management protocol that featured preferential use of eEVAR (n=18); patients with unsuitable anatomy or who were hemodynamically unstable underwent open repair (n=31). Mortality data and costs of treatment were compared in this mixed prospective group to a historical control group consisting of 147 patients (128 men; mean age 71 years) who underwent open repair from January 1998 to December 2001. All direct medical costs were included from the moment of admission until discharge from the hospital. RESULTS: Mortality in the mixed prospective group (18%) was lower than in the historical control group (31%), but the difference did not reach statistical significance (p=0.099). The mean total cost in the mixed prospective group was 17,164 euro compared to 21,084 euro in the historical open repair group (p=0.255). CONCLUSION: A preferential eEVAR protocol for acute AAA can decrease mortality and does not increase overall costs during initial treatment, but larger studies are needed to determine if these trends are statistically significant.

Cost-effectiveness of neonatal screening for medium chain acyl-CoA dehydrogenase deficiency: the homogeneous population of The Netherlands.

OBJECTIVE: To assess the cost-effectiveness of neonatal screening on medium chain acyl-CoA dehydrogenase (MCAD) deficiency in a homogeneous population. STUDY DESIGN: For the scenario without neonatal screening, medical chart review and interviews were performed with physicians and families of 116 Dutch patients born between 1985 and July 2003 with clinically ascertained MCAD deficiency. For the scenario with neonatal screening, 66,205 unaffected and 11 affected newborns identified by prospective neonatal screening for MCAD deficiency in the northern part of the Netherlands were evaluated. The incremental cost-effectiveness ratio (ICER) used life years (LYs) as the outcome measure by combining both scenarios in a decision model with second-order Monte Carlo simulation. RESULTS: For the scenarios with and without neonatal screening for MCAD deficiency, costs were $6.10 and $4.22 per newborn, respectively. The main cost categories were institutionalization (64%), admissions (17%), special education (8%), laboratory testing (4%), and (para)medical contact (4%). The resulting ICER was $1653 per LY gained. Sensitivity analysis generated an ICER between $14,839 and $4345 per LY gained. CONCLUSIONS: Screening for MCAD deficiency in a well-defined population generates an ICER well within accepted boundaries for cost-effective interventions, even after sensitivity analysis.

Nonanastomotic biliary strictures after liver transplantation, part 1: Radiological features and risk factors for early vs. late presentation.

Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). The exact pathogenesis is unclear. Purpose of this study was to identify risk factors for the development of NAS after OLT. A total of 487 adult liver transplants with a median follow-up of 7.9 years were studied. All imaging studies of the biliary tree were reviewed. Cholangiography was routinely performed between postoperative days 10-14 and later on demand. Localization of NAS at first presentation was categorized into 4 anatomical zones of the biliary tree. Severity of NAS was semiquantified as mild, moderate, or severe. Donor, recipient, and surgical characteristics and variables were analyzed to identify risk factors for NAS. NAS developed in 81 livers (16.6%). Thirty-seven (7.3%) were graded as moderate to severe. In 85% of the cases, anatomical localization of NAS was around or below the bifurcation of the common bile duct. A large variation was observed in the time interval between OLT and first presentation of NAS (median 4.1 months; range 0.3-155 months). NAS presenting early (< or =1 year) after OLT were associated with preservation-related risk factors. Cold and warm ischemia times were significantly longer in patients with early NAS compared with NAS presenting late (>1 year) after OLT (694 minutes vs. 490 minutes, P = 0.01, and 57 minutes vs. 53 minutes, P < 0.05, respectively), and early NAS were more frequently located in the central bile ducts. NAS presenting late (>1 year) after OLT were found more frequently in the periphery of the liver and were more frequently associated with immunological factors, such as primary sclerosing cholangitis, as the indication for OLT (24% vs. 45%, P < 0.05). By separating cases of NAS on the basis of the time of presentation after transplantation, we were able to identify differences in risk factors, indicating different pathogenic mechanisms depending on the time of initial presentation.

Safe and unsafe duration of fasting for children with MCAD deficiency.

OBJECTIVE: To study the safe and unsafe duration of fasting in children with medium chain acyl-Coenzyme A dehydrogenase (MCAD) deficiency, the literature and the database on Dutch MCAD-deficient patients were searched for data on fasting studies in patients with MCAD deficiency. MATERIALS AND METHODS: These data were extended with information on fasting studies performed on our patients with MCAD deficiency known in the Beatrix Children's Hospital, UMC Groningen, The Netherlands. The data reflect considerable inter-individual variation and overlap between safe and unsafe duration of fasting. RESULTS: In six out of 35 fasting tests, symptoms were reported before hypoglycaemia was observed. Until 1 year of age, the median safe and unsafe duration of fasting was 12 hours (n=7, range 8-19 hours) and 18 hours (n=5, range 15-20 hours), respectively. After the first year of life, the median safe and unsafe duration of fasting was 18 hours (n=17, range 10-24 hours) and 20 hours (n=9, range 13-32 hours), respectively. CONCLUSION: Therefore, to conclude, we recommend a maximum duration of fasting in children with MCAD deficiency of 8 hours between 6 months and 1 year of age, 10 hours in the second year of life and 12 hours thereafter. From this study, no conclusions can be drawn on the duration of fasting during situations of intercurrent illness, especially with fever.

Surgical injuries of postmortem donor livers: incidence and impact on outcome after adult liver transplantation.

The exact frequency and clinical consequences of surgical hepatic injuries during organ procurement are unknown. We analyzed the incidence, risk factors, and clinical outcome of surgical injuries in 241 adult liver grafts. Hepatic injuries were categorized as parenchymal, vascular, or biliary. Outcome variables were bleeding complications, hepatic artery thrombosis (HAT), and graft survival. In 82 livers (34%), 96 injuries were detected. Most injuries were minor, but clinically relevant injuries were detected in 6.6% (16/241) of the livers. Fifty (21%) liver grafts had some degree of parenchymal or capsular injury, 40 (17%) had vascular injury, and 6 (2%) had an injury to the bile duct. Procurement region was the only risk factor significantly associated with surgical injury. The rate of hepatic artery injury was significantly higher in livers with aberrant arterial anatomy. Bleeding complications were found in 18% of patients who received livers with a parenchymal or capsular injury in contrast to 9% without parenchymal injury (P = 0.065). HAT was found in 23% of the patients who received a liver with arterial injury compared to 4% without arterial injury (P = 0.001). Overall graft survival rates were not significantly different for grafts with or without anatomical injury. In conclusion, surgical injuries of donor livers are an underestimated problem in liver transplantation and can be observed in about one-third of all cases. Clinically relevant injuries are detected in 6.6% of all liver grafts. Arterial injuries are associated with an increased risk of HAT.

Noninferiority testing in cost-minimization studies: Practical issues concerning power analysis.

OBJECTIVES: In cost-minimization studies, it is important to establish noninferiority in the clinical effect of the treatments under investigation. The relationship between the proportion of patients reaching the end point in a study, equivalence limit (delta), and power is investigated in the context of cost-minimization studies with dichotomous clinical end points. Two formulations of the null-hypothesis, absolute and relative formulations of delta, will be explored. METHODS: Sensitivity analysis was performed, in which the effect of the predicted proportions and delta on the power in a noninferiority setting was investigated. The patterns found are discussed in terms of the practical relevance within the cost-minimization framework. RESULTS: Sensitivity analyses show different patterns of results for both null-hypotheses. The differences in these results originate from the way delta is expressed. By expressing delta as absolute difference, power grows quite fast when sample proportions are smaller than expected. In the case of a proportional delta at small sample proportions, the power to establish noninferiority remains low. CONCLUSIONS: To obtain valid results from a cost-minimization study, care has to be taken to adapt the correct methodology for noninferiority testing in clinical outcomes. Defining delta in terms of absolute differences between treatments can lead to obscured results. Although conservative, the expression of delta as a proportion of the effectiveness of the treatment as usual is found to be closer to clinical practice. The inflated delta, resulting from smaller clinical effects than expected when absolute formulation is applied, thus can be avoided.