Enhancing Preoperative Outcome Prediction: A Comparative Retrospective Case-Control Study on Machine Learning versus the International Esodata Study Group Risk Model for Predicting 90-Day Mortality in Oncologic Esophagectomy.

Risk prediction prior to oncologic esophagectomy is crucial for assisting surgeons and patients in their joint informed decision making. Recently, a new risk prediction model for 90-day mortality after esophagectomy using the International Esodata Study Group (IESG) database was proposed, allowing for the preoperative assignment of patients into different risk categories. However, given the non-linear dependencies between patient- and tumor-related risk factors contributing to cumulative surgical risk, machine learning (ML) may evolve as a novel and more integrated approach for mortality prediction. We evaluated the IESG risk model and compared its performance to ML models. Multiple classifiers were trained and validated on 552 patients from two independent centers undergoing oncologic esophagectomies. The discrimination performance of each model was assessed utilizing the area under the receiver operating characteristics curve (AUROC), the area under the precision-recall curve (AUPRC), and the Matthews correlation coefficient (MCC). The 90-day mortality rate was 5.8%. We found that IESG categorization allowed for adequate group-based risk prediction. However, ML models provided better discrimination performance, reaching superior AUROCs (0.64 [0.63-0.65] vs. 0.44 [0.32-0.56]), AUPRCs (0.25 [0.24-0.27] vs. 0.11 [0.05-0.21]), and MCCs (0.27 ([0.25-0.28] vs. 0.15 [0.03-0.27]). Conclusively, ML shows promising potential to identify patients at risk prior to surgery, surpassing conventional statistics. Still, larger datasets are needed to achieve higher discrimination performances for large-scale clinical implementation in the future.

The Impact of the COVID-19 Pandemic on Esophageal and Gastric Cancer Surgery in Germany: A Four-Year Retrospective Single-Center Study of 287 Patients.

Background: Disruptions to surgical care for cancer patients during the COVID-19 pandemic remain an ongoing debate. This study assesses the effects of the COVID-19 pandemic on perioperative outcomes in a continuous series of surgically treated esophageal and gastric carcinoma patients at a large university hospital in Europe over 48 months. Methods: We conducted a retrospective single-center cohort study at a tertiary referral center. All patients who underwent oncologic esophageal or gastric resection between March 2018 and February 2022 were included in the analysis. The sample was split into a 24 months COVID-19 and an equivalent pre-COVID-19 control period. Outcome variables included caseload, in-hospital mortality, morbidity, treatment course, and disease stage at presentation. Results: Surgeons performed 287 operations, with around two-thirds (62%) of the cohort undergoing esophagectomy and one-third (38%) gastrectomy. The in-hospital mortality was 1% for the COVID-19 and the control periods. Patients did not present at a later disease stage nor did they wait longer for treatment. There was no decrease in caseload, and patients did not suffer from more perioperative complications during COVID-19. Conclusions: Esophageal and gastric carcinoma patients received safe and timely surgical care during the pandemic. Future pandemic protocols may streamline oncologic care towards tertiary referral centers.

Use and accuracy of decision support systems using artificial intelligence for tumor diseases: a systematic review and meta-analysis.

Background: For therapy planning in cancer patients multidisciplinary team meetings (MDM) are mandatory. Due to the high number of cases being discussed and significant workload of clinicians, Clinical Decision Support System (CDSS) may improve the clinical workflow. Methods: This review and meta-analysis aims to provide an overview of the systems utilized and evaluate the correlation between a CDSS and MDM. Results: A total of 31 studies were identified for final analysis. Analysis of different cancers shows a concordance rate (CR) of 72.7% for stage I-II and 73.4% for III-IV. For breast carcinoma, CR for stage I-II was 72.8% and for III-IV 84.1%, P≤ 0.00001. CR for colorectal carcinoma is 63% for stage I-II and 67% for III-IV, for gastric carcinoma 55% and 45%, and for lung carcinoma 85% and 83% respectively, all P>0.05. Analysis of SCLC and NSCLC yields a CR of 94,3% and 82,7%, P=0.004 and for adenocarcinoma and squamous cell carcinoma in lung cancer a CR of 90% and 86%, P=0.02. Conclusion: CDSS has already been implemented in clinical practice, and while the findings suggest that its use is feasible for some cancers, further research is needed to fully evaluate its effectiveness.

Concordance of a decision algorithm and multidisciplinary team meetings for patients with liver cancer-a study protocol for a randomized controlled trial.

INTRODUCTION: Multidisciplinary team meetings (MDMs), also known as tumor conferences, are a cornerstone of cancer treatments. However, barriers such as incomplete patient information or logistical challenges can postpone tumor board decisions and delay patient treatment, potentially affecting clinical outcomes. Therapeutic Assistance and Decision algorithms for hepatobiliary tumor Boards (ADBoard) aims to reduce this delay by providing automated data extraction and high-quality, evidence-based treatment recommendations. METHODS AND ANALYSIS: With the help of natural language processing, relevant patient information will be automatically extracted from electronic medical records and used to complete a classic tumor conference protocol. A machine learning model is trained on retrospective MDM data and clinical guidelines to recommend treatment options for patients in our inclusion criteria. Study participants will be randomized to either MDM with ADBoard (Arm A: MDM-AB) or conventional MDM (Arm B: MDM-C). The concordance of recommendations of both groups will be compared using interrater reliability. We hypothesize that the therapy recommendations of ADBoard would be in high agreement with those of the MDM-C, with a Cohen's kappa value of ≥ 0.75. Furthermore, our secondary hypotheses state that the completeness of patient information presented in MDM is higher when using ADBoard than without, and the explainability of tumor board protocols in MDM-AB is higher compared to MDM-C as measured by the System Causability Scale. DISCUSSION: The implementation of ADBoard aims to improve the quality and completeness of the data required for MDM decision-making and to propose therapeutic recommendations that consider current medical evidence and guidelines in a transparent and reproducible manner. ETHICS AND DISSEMINATION: The project was approved by the Ethics Committee of the Charité - Universitätsmedizin Berlin. REGISTRATION DETAILS: The study was registered on ClinicalTrials.gov (trial identifying number: NCT05681949; https://clinicaltrials.gov/study/NCT05681949 ) on 12 January 2023.

Textbook Outcome after Gastrectomy for Gastric Cancer Is Associated with Improved Overall and Disease-Free Survival.

(1) Background: The complexity of the perioperative outcome for patients with gastric cancer is not well reflected by single quality metrics. To study the effect of the surgical outcome on survival, we have evaluated the relationship between textbook outcome (TO)-a new composite parameter-and oncological outcome. (2) Methods: All patients undergoing total gastrectomy or trans-hiatal extended gastrectomy for gastric cancer with curative intent between 2017 and 2021 at our institution were included. TO was defined by negative resection margins (R0); collection of ≥25 lymph nodes; the absence of major perioperative complications (Clavien-Dindo ≥ 3); the absence of any reintervention; absence of unplanned ICU re-admission; length of hospital stay < 21 days; absence of 30-day readmission and 30-day mortality. We evaluated factors affecting TO by multivariate logistic regression. The correlation between TO and long-term survival was assessed using a multivariate cox proportional-hazards model. (3) Results: Of the patients included in this study, 52 (52.5 %) achieved all TO metrics. Open surgery (p = 0.010; OR 3.715, CI 1.334-10.351) and incomplete neoadjuvant chemotherapy (p = 0.020, OR 4.278, CI 1.176-15.553) were associated with failure to achieve TO on multivariate analysis. The achievement of TO significantly affected overall survival (p = 0.015). TO (p = 0.037, OD 0.448, CI 0.211-0.954) and CCI > 4 (p = 0.034, OR 2.844, CI 1.079-7.493) were significant factors affecting DFS upon univariate analysis. In multivariate analysis, CCI > 4 (p = 0.035, OR 2.605, CI 0.983-6.905) was significantly associated with DFS. (4) Conclusions: We identified patient- and procedure-related factors influencing TO. Importantly, achieving TO is strongly associated with improved long-term survival in gastric cancer patients and merits further focus on surgical quality improvement efforts.

Robotic-Assisted Ivor Lewis Esophagectomy Is Safe and Cost Equivalent Compared to Minimally Invasive Esophagectomy in a Tertiary Referral Center.

In recent decades, robotic-assisted minimally invasive esophagectomy (RAMIE) has been increasingly adopted for patients with esophageal cancer (EC) or cancer of the gastroesophageal junction (GEJ). However, concerns regarding its costs compared to conventional minimally invasive esophagectomy (MIE) have emerged. This study examined outcomes and costs of RAMIE versus total MIE in 128 patients who underwent Ivor Lewis esophagectomy for EC/GEJ at our department between 2017 and 2021. Surgical costs were higher for RAMIE (EUR 12,370 vs. EUR 10,059, p < 0.001). Yet, median daily (EUR 2023 vs. EUR 1818, p = 0.246) and total costs (EUR 30,510 vs. EUR 29,180, p = 0.460) were comparable. RAMIE showed a lower incidence of postoperative pneumonia (8% vs. 25%, p = 0.029) and a trend towards shorter hospital stays (15 vs. 17 days, p = 0.205), which may have equalized total costs. Factors independently associated with higher costs included readmission to the intensive care unit (hazard ratio [HR] = 7.0), length of stay (HR = 13.5), anastomotic leak (HR = 17.0), and postoperative pneumonia (HR = 5.4). In conclusion, RAMIE does not impose an additional financial burden. This suggests that RAMIE may be considered as a valid alternative approach for esophagectomy. Attention to typical cost factors can enhance postoperative care across surgical methods.

The Learning Curve for Hand-Assisted Laparoscopic Total Gastrectomy in Gastric Cancer Patients.

(1) Background: Hand-assisted laparoscopic total gastrectomy (LTG) for patients with gastric cancer (GC) has been established as the standard surgical treatment at our center. This study aims to quantify the learning curve for surgeons performing minimally invasive total gastrectomy at a high-volume single center. (2) Methods: One hundred and eighteen consecutive patients who underwent minimally invasive total gastrectomy between January 2014 and December 2020 at a single high-volume center were included and reviewed retrospectively. Risk-adjusted cumulative sum analysis (RA-CUSUM) was used to monitor the surgical outcomes for patients with different risks of postoperative mortality using varying-coefficient logistic regression models. Patients were ordered by the sequential number of the procedure performed and divided into two groups according to the degree of surgeon proficiency as determined by RA-CUSUM analysis (group A: 45; group B: 73 patients). Age, gender, body mass index (BMI), tumor location, pathology, and comorbidities were compared while primary endpoints comprised surgical parameters, postoperative course, and survival outcomes. (3) Results: Forty-four cases were required for the completion of the learning curve. During this time, the mean operating time decreased. Hand-assisted laparoscopic total gastrectomy performed after a learning curve was associated with a shorter median operating time (OT) (360 min vs. 289 min, <0.001), and a reduced length of stay (A = 18.0 vs. B = 14.0 days) (p = 0.154), while there was a trend toward less major complications (Clavien−Dindo (CD) 3−5 within 90 days (12 (26.67%) vs. 10 (13.70%) p = 0.079). Our results showed no difference in anastomotic leakage between the two groups (group A vs. group B, 3 (6.67%) vs. 4 (5.48%) p = 0.99). Similarly, 30-day (0 (0%) vs. 1 (1.7%), p = 0.365) and 90-day mortality (1 (2.08%) vs. 2 (3.39%), p = 0.684) were comparable. Following multivariate analysis, the level of surgical proficiency was not a significant prognostic factor for overall survival. (4) Conclusions: A minimum of 44 cases are required for experienced laparoscopic surgeons to achieve technical competence for performing LTG. While operation time decreased after completion of the learning curve, quality criteria such as achievement of R0 resection, anastomotic leakage, and perioperative mortality remained unaltered. Of note, the level of surgical training showed no significant impact on the 2 year OS or DFS.

The Association between Neoadjuvant Radio-Chemotherapy and Prolonged Healing of Anastomotic Leakage after Esophageal Resection Treated with EndoVAC Therapy.

(1) Background: Endoscopic vacuum therapy (EVT) has become the mainstay in the treatment of early anastomotic leakage (AL) after esophageal resection. The effect of nRCT on the efficacy of EVT is currently unknown. (2) Methods: Data of 427 consecutive patients undergoing minimally invasive esophagectomy between 2013 and 2022 were analyzed. A total of 26 patients received EVT for AL after esophagectomy between 2010 and 2021. We compared a cohort of 13 patients after treatment with EVT for anastomotic leakage after neoadjuvant radiochemotherapy (nRCT) with a control group of 13 patients after neoadjuvant chemotherapy (nCT) using inverse propensity score weighting to adjust for baseline characteristics between the groups. EVT therapy was assessed regarding patient survival, treatment failure as defined by a change in treatment to stent/operation, duration of treatment, and secondary complications. Statistical analysis was performed using linear regression analysis. (3) Results: Time to EVT after initial tumor resection did not vary between the groups. The duration of EVT was longer in patients after nRCT (14.69 days vs. 20.85 days, p = 0.002) with significantly more interventions (4.38 vs. 6.85, p = 0.001). The success rate of EVT did not differ between the two groups (nCT n = 8 (61.54%) vs. nCT n = 5 (38.46%), p = 0.628). The rate of operative revision did not vary between the groups. Importantly, no mortality was reported within 30 days and 90 days in both groups. (4) Conclusions: EVT is a valuable tool for the management of AL after esophageal resection in patients after nRCT. While the success rates were comparable, EVT was associated with a significantly longer treatment duration. Anastomotic leakages after nRCT often require prolonged and multimodal treatment strategies while innovative strategies such as prophylactic endoVAC placement or use of a VAC-Stent may be considered.

Robotic versus open pancreatic surgery: a propensity score-matched cost-effectiveness analysis.

BACKGROUND: Robotic pancreatic surgery (RPS) is associated with high intraoperative costs compared to open pancreatic surgery (OPS). However, it remains unclear whether several advantages of RPS such as reduced surgical trauma and a shorter postoperative recovery time could lead to a reduction in total costs outweighing the intraoperative costs. The study aimed to compare patients undergoing OPS and RPS with regards to cost-effectiveness in a propensity score-matched (PSM) analysis. METHODS: Patients undergoing OPS and RPS between 2017 and 2019 were included in this monocentric, retrospective analysis. The controlling department provided financial data (costs and revenues, net loss/profit). A propensity score-matched analysis was performed or OPS and RPS (matching criteria: age, American society of anesthesiologists (ASA) score, gender, body mass index (BMI), and type of pancreatic resection) with a caliper 0.2. RESULTS: In total, 272 eligible OPS cases were identified, of which 252 met all inclusion criteria and were thus included in the further analysis. The RPS group contained 92 patients. The matched cohorts contained 41 patients in each group. Length of hospital stay (LOS) was significantly shorter in the RPS group (12 vs. 19 days, p = 0.003). Major postoperative morbidity (Dindo/Clavien ≥ 3a) and 90-day mortality did not differ significantly between OPS and RPS (p > 0.05). Intraoperative costs were significantly higher in the RPS group than in the OPS group (7334€ vs. 5115€, p < 0.001). This was, however, balanced by other financial categories. The overall cost-effectiveness tended to be better when comparing RPS to OPS (net profit-RPS: 57€ vs. OPS: - 2894€, p = 0.328). Binary logistic regression analysis revealed major postoperative complications, longer hospital stay, and ASA scores < 3 were linked to the risk of net loss (i.e., costs > revenue). CONCLUSIONS: Surgical outcomes of RPS were similar to those of OPS. Higher intraoperative costs of RPS are outweighed by advantages in other categories of cost-effectiveness such as decreased lengths of hospital stay.

Perioperative Risk Assessment in Pancreatic Surgery Using Machine Learning.

Pancreatic surgery is associated with a high risk for postoperative complications and death of patients. Complications occur in a variable interval after the procedure. Often, a patient has already left the ICU and is not properly monitored anymore when the complication occurs. Risk stratification models can assist in identifying patients at risk in order to keep these patients in ICU for longer. This, in turn, helps to identify complications earlier and increase survival rates. We trained multiple machine learning models on pre-, intra- and short term postoperative data from patients who underwent pancreatic resection at the Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin. The presented models achieve an area under the precision-recall curve (AUPRC) of up to 0.51 for predicting patient death and 0.53 for predicting a specific major complication. Overall, we found that a classical logistic regression model performs best for the investigated classification tasks. As more patient data becomes available throughout the perioperative stay, the performance of the risk stratification model improves and should therefore repeatedly be computed.

Intrahepatic De Novo Tumors in Liver Recipients are Highly Associated With Recurrent Viral Hepatitis.

BACKGROUND/AIMS: Long-term survival of liver transplant recipients is endangered by tumorigenesis at different sites. Little is known about primary de novo tumors developing in the graft. METHODS: We analyzed the follow-up data of 2731 liver recipients that were transplanted between 1988 and 2019 at our institution (Charité - Universitätsmedizin Berlin, Department of Surgery). All cases with new intrahepatic tumors during follow-up were identified. RESULTS: A total of nine patients were diagnosed at a median of 16 years (range, 2-24 years) after surgery. Eight patients presented with hepatocellular carcinoma (HCC), and one patient presented with epithelioid hemangioendothelioma (EHE). All eight HCC patients had a recurrence of the initial disease that had caused liver failure before transplantation. This was associated with viral reinfection with either HCV or HBV in seven cases. Of the nine patients, three underwent surgical resection and only one patient was alive at data abstraction. CONCLUSION: Intrahepatic de novo neoplasms in the liver graft need to be considered in the long-term follow-up of liver recipients and were strongly associated with recurrent viral hepatitis in our study. Although prognosis of this rare complication is generally poor, patients may benefit from surgical resection of localized disease.

Composite tissue allotransplantation: opportunities and challenges.

Vascularized composite allotransplants (VCAs) have unique properties because of diverse tissue components transplanted en mass as a single unit. In addition to surgery, this type of transplant also faces enormous immunological challenges that demand a detailed analysis of all aspects of alloimmune responses, organ preservation, and injury, as well as the immunogenicity of various tissues within the VCA grafts to further improve graft and patient outcomes. Moreover, the side effects of long-term immunosuppression for VCA patients need to be carefully balanced with the potential benefit of a non-life-saving procedure. In this review article, we provide a comprehensive update on limb and face transplantation, with a specific emphasis on the alloimmune responses to VCA, established and novel immunosuppressive treatments, and patient outcomes.

Evaluation of histological dynamics, kidney function and diabetes in liver transplant patients after antiviral treatment with direct-acting antivirals: Therapy of HCV-recurrence.

BACKGROUND: Direct-acting antivirals allow efficient and safe treatment of hepatitis C (HCV) before and after liver transplantation (LT). However, the impact of sofosbuvir on the graft, diabetes, and on kidney function is not answered yet. Primary endpoint of this analysis was the evaluation of kidney function after antiviral treatment (AVT). Secondary endpoints were the assessment of extrahepatic manifestation of HCV-infection by diabetes mellitus and the histopathological changes in terms of inflammation, content of fat, and fibrosis stage. METHODS: From 2014 to 4/2015, 100 patients with HCV-recurrence after LT were successfully treated with AVT. Ninety-eight received a sofosbuvir-based regimen. Indication was based on genotype, transplant fibrosis stage, and urgency. Biopsies were evaluated before and after treatment. Renal function and diabetes were assessed before, during, and after AVT. RESULTS: All patients achieved sustained virological response. A significant improvement of inflammation (P = 0.001) and fibrosis stage (P = 0.031) were observed. Significantly less insulin was required in 32 patients with diabetes (P < 0.001) to keep Hb1Ac unchanged after AVT. Kidney function was stable during, 12 weeks after and 48 weeks after antiviral therapy. Stages of renal insufficiency were comparable before and after AVT. CONCLUSION: Successful sofosbuvir-based AVT leads to a variety of positive development in transplant patients including a significant improvement of inflammation, fat content and fibrosis, a significant decrease in daily insulin dose and no significant impairment of kidney function.

Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience.

BACKGROUND: Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. METHODS: Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. RESULTS: HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. CONCLUSIONS: Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.

Efficacy of a long-term home parenteral nutrition regimen containing fish oil-derived n-3 polyunsaturated fatty acids: a single-centre, randomized, double blind study.

BACKGROUND: Data on the use of lipid emulsions containing fish-oil (FO) derived n-3 polyunsaturated fatty acids (n-3 PUFAs) in addition to medium- and long-chain triglycerides (MCT/LCT) for long-term home parenteral nutrition (HPN) are limited. This study aimed to compare HPN regimens containing either MCT/LCT/FO-derived n-3 PUFAs (test group) or MCT/LCT (control group) with respect to efficacy and safety during 8 weeks of HPN using a non-inferiority trial design with change of body mass index (BMI) as primary endpoint. METHODS: This prospective, randomized, double-blind study was conducted at the Charité, Berlin, Germany, from 02/2008 until 01/2014. Adult patients (n = 42; aged 18 to 80 years) requiring HPN for at least 8 weeks were randomly assigned to the test or control group. Assessments included weight, height, physical examination (cardiovascular system, abdomen, respiratory tract, liver, spleen, kidney, urine tract, skin, mucous membrane, neurology, psyche, musculoskeletal system, lymph nodes), bio impedance analysis, calorimetry, blood samplings (haematology, biochemistry, fatty acid analysis) and quality of life questionnaire. RESULTS: BMI increased in both groups with 8 weeks of HPN (ΔBMI(test group) = 1.3 ± 1.1 kg/m2; ΔBMI(control group) = 0.6 ± 0.9 kg/m2) demonstrating non-inferiority of the test regimen regarding nutritional efficacy. Assessment of secondary efficacy endpoints revealed that after 8 weeks of HPN with the test regimen, the proportion of n-3 PUFAs in serum, platelet and red blood cell phospholipids significantly increased, while the proportion of n-6 PUFAs decreased. The fatty acid pattern in the control group remained mostly stable. No statistically significant differences were detected between groups regarding inflammatory markers or quality of life. Laboratory parameters reflecting the safety endpoints liver function, bone metabolism, renal function, metabolic activity, lipid metabolism, coagulation and haematology were stable in both groups and no group differences were detected regarding (serious) adverse events. CONCLUSIONS: The HPN regimen prepared with MCT/LCT/FO-derived n-3 PUFAs was at least as efficient in maintaining or even improving nutritional status during HPN as the control MCT/LCT regimen. Administration of FO-derived n-3 PUFAs for 8 weeks altered the fatty acid pattern of serum, platelet and red blood cell phospholipids. Both regimens were safe and well tolerated. TRIAL REGISTRATION: www.clinicaltrials.gov , registration number: NCT00530738.

Monitoring the removal efficiency of pharmaceuticals and hormones in different treatment processes of source-separated urine with bioassays.

Urine can be collected separately from the general wastewater with the aim of recycling the nutrients. Urine source-separation not only prevents wasting nutrients but also prevents potentially hazardous micropollutants from entering the wastewater stream and tainting a final fertilizer product. We assessed various urine treatment technologies for their performance to remove micropollutants such as pharmaceuticals, natural and synthetic steroid hormones, and their human biotransformation products. Removal efficiencies were determined with a combination of bioassays and chemical target analysis. The yeast estrogen screen yielded information on estrogenicity. Specific phytotoxicity and nonspecific baseline toxicity was determined with an algae chlorophyll fluorescence test. Filtration methods, such as nanofiltration and electrodialysis, were highly efficient with respect to toxicity reduction. Micropollutant degradation during biological treatment in a sequencing batch reactor was very compound specific. Ozonation removed the target analytes and the estrogenicity completely, but the baseline toxicity was only reduced by 50-60% depending on the ozone doses. Struvite precipitation produced a very "clean" fertilizer product that is ready to use. The examples show that bioassays and chemical analysis yield complementary information, but are very useful to monitor treatment efficiencies and to assess the ecotoxicological potential of byproducts of urine treatment processes. The results of this study present a method to assess the micropollutant removal efficiency, and therefore, support the choice of an appropriate urine processing technique for real-world applications.

Screening test battery for pharmaceuticals in urine and wastewater.

A test battery for identifying ecotoxicological hazards was applied to six pharmaceuticals (carbamazepine, diclofenac, ethinylestradiol, ibuprofen, propranolol, and sulfamethoxazole), to their mixtures, and to urine spiked with pharmaceuticals to test the suitability of biotests for screening urine and wastewater and for monitoring the efficiency of wastewater treatment. The test battery comprised the bioluminescence inhibition test with Vibrio fischeri, the yeast estrogen screen, and a photosynthesis inhibition assay in algae based on chlorophyll fluorescence measurements. Mixture and additional experiments with a cocktail of pharmaceuticals added to urine confirmed the applicability of the test systems as an integrated measure of the overall micropollutant burden. Because the concentration of pharmaceuticals in wastewater is low and the nutrients and salts may have a negative impact on the bioassays, urine and wastewater samples were cleaned and concentrated by solid-phase extraction (SPE). The compounds of interest ranged from polar to nonpolar and from positively charged to neutral and negatively charged. Consequently, the SPE method was optimized for universality rather than for specificity. Results of preliminary experiments with raw and treated urine and wastewater indicate the suitability of the proposed test battery for screening urine and wastewater.