Temporal Trends in Urinary Diversion among Patients Undergoing Radical Cystectomy Between 1986 and 2022: Experience at the University Medical Center Mainz with 2224 Cases.

BACKGROUND: Analysis of temporal trends of urinary diversion (UD) and identification of predictive factors for continent urinary diversion (CUD) in patients with bladder cancer (BC) is scarce and data on large cohorts are missing. We aimed to describe longitudinal temporal trends and predictive factors for UD among patients with BC receiving radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed institutional data collected from patients undergoing RC from 1986 to 2022 to describe changes in patients' characteristics and UD. Primary end points were patients' characteristics associated with type of UD. Logistic regression analysis was used to determine predictive factors for CUD. RESULTS: In total, 2224 patients (77.16% male, 22.84% female) with a mean age of 66 years [standard deviation (SD), 10.64 years] were included. We observed an increase in mean age from 59.86 (10.8) years (1986-1990) to 69.85 (9.99) years (2016-2022) (p < 0.001). The proportion of CUD gradually declined from 43.72% (94/215; 1986-1990) to 18.38% (86/468; 2016-2022). Patients who were male [odds ratio (OR): 1.92, 95% confidence interval (CI): 1.43-2.57, p < 0.001), younger (OR: 0.88, 95% CI: 0.87-0.89, p < 0.001) and had no hydronephrosis prior to RC (OR: 2.2, 95% CI: 1.66-2.92, p < 0.001) were more likely to receive CUD. CONCLUSIONS: We report the largest European single-center cohort of UD after RC, demonstrating a significant shift from CUD to IUD, accompanied by an increasing age. Finally, our data mirrors the development and extensive experience with the Mainz Pouch-I in the 1980's and 1990's together with other colon pouches.

Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study.

PURPOSE: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. METHODS: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3-5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. RESULTS: Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05). CONCLUSION: We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

PURPOSE: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. MATERIALS AND METHODS: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. RESULTS: In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. CONCLUSIONS: The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Radical cystectomy in patients aged < 80 years versus ≥ 80 years: analysis of preoperative geriatric assessment scores in predicting postoperative morbidity and mortality.

PURPOSE: Pre-operative assessment of surgical risk is essential for patient counselling in the elderly patient population. Our purpose was to compare validated geriatric assessment scores (GAS) in predicting postoperative morbidity and mortality in patients ≥ 80 years. METHODS: Overall, eight preoperative GAS were assessed for each patient who received RC from 2016 to 2021. Postoperative morbidity was recorded according to the Clavien-Dindo classification (CDC) of surgical complications. Binary logistic regression analyses were used to determine prediction of 30-d morbidity and 90-d mortality in patients ≥ 80 years. RESULTS: In total, 424 patients were analysed (77.4% male) with median age of 71 years (IQR: 68.82;70.69), of which 67 (15.8%) were ≥ 80 years. Patients age ≥ 80 years showed more 30-d CDC grade ≥ IIIb (41.07% vs. 27.74% compared to < 80 years, p < .001) and worse 90-d mortality (26.87% vs. 4.76%, p < .001). In patients ≥ 80 years, morbidity was predicted by simplified Frailty Index (sFI)  ≥ 2 (OR: 2.06, 95% CI: 1.27-3.34, p = .004), Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (OR: 2.78, 95% CI: 1.18-6.54, p = .019) and severe Adult Comorbidity Evaluation (ACE)-27 score (OR: 2.07, 95% CI: 1.13-3.79, p = .019), while 90-d mortality was predicted by CDC grade ≥ IIIb (OR: 22.91, 95% CI: 8.74-60.09, p < .001) and ECOG ≥ 2 (OR: 2.87, 95% CI: 1.05-7.86, p = .04). CONCLUSION: Even in a high-volume center of RC, 90-d mortality is significantly higher in patients age ≥ 80. Our results suggest in patient age ≥ 80, sFI ≥ 2, ECOG performance status ≥ 2 and severe ACE-27 score as clinical cut-off value to evaluate alternative bladder-sparing concepts.

Comparative Retrospective Assessment of the Effectiveness and Risk Factors of Fluoroquinolones, Cephalosporines, and Selective Antibiotic Prophylaxis for Transrectal Prostate Biopsy.

INTRODUCTION: Despite increasing resistance of enterobacteria against fluoroquinolones (FLU), they are still widely used during transrectal prostate biopsy (TRPB). This study was designed to analyse infectious complications and risk factors between FLU, cephalosporines (CEPH) and selective other antibiotics (O-AB) used during TRPB. METHODS: 664 patients were included retrospectively (152 FLU, 452 CEPH and 60 O-AB). Infectious complications were defined as fever >38.0°C, the in-house definition of complicated urinary tract infection (cUTI) (if all applied: fever >38.0°C, leucocytosis >11.000/µL and positive urine dipstick) or postinterventional bacteriuria. Hospitalisation rate, duration and comorbidities were also assessed. χ2 and Fisher's exact test were used for group comparison. Multivariate regression analysis assessed the association of comorbidities with infectious complications. RESULTS: FLU and CEPH were indifferent regarding infectious complications, however in the O-AB group significantly more common compared to FLU and CEPH (11.6, 13.3, 25%, p < 0.05). Duration of hospital stay in CEPH was significantly shorter compared to FLU and O-AB (4.1 vs. 6.3 vs. 8.2 days, p < 0.05). Arterial hypertension showed increased association with fever (OR 6.002 (1.178; 30.597) p = 0.031) and cUTI (OR 6.006 (1.207; 29.891) p = 0.029). CONCLUSION: Infectious complications were low and indifferent between FLU and CEPH but significantly more frequent in O-AB. Arterial hypertension was significantly associated with postinterventional fever and cUTI.

Single-center, prospective phase 2 trial of high-intensity focused ultrasound (HIFU) in patients with unilateral localized prostate cancer: good functional results but oncologically not as safe as expected.

PURPOSE: Focal therapy (FT) for localized prostate cancer (PCa) is only recommended within the context of clinical trials by international guidelines. We aimed to investigate oncological follow-up and safety data of focal high-intensity focused ultrasound (HIFU) treatment. METHODS: We conducted a single-center prospective study of 29 patients with PCa treated with (focal) HIFU between 2016 and 2021. Inclusion criteria were unilateral PCa detected by mpMRI-US-fusion prostate biopsy and maximum prostate specific antigen (PSA) of 15 ng/ml. Follow-up included mpMRI-US fusion-re-biopsies 12 and 24 months after HIFU. No re-treatment of HIFU was allowed. The primary endpoint was failure-free survival (FFS), defined as freedom from intervention due to cancer progression. RESULTS: Median follow-up of all patients was 23 months, median age was 67 years and median preoperative PSA was 6.8 ng/ml. One year after HIFU treatment PCa was still detected in 13/ 29 patients histologically (44.8%). Two years after HIFU another 7/29 patients (24.1%) were diagnosed with PCa. Until now, PCa recurrence was detected in 11/29 patients (37.93%) which represents an FFS rate of 62%.One patient developed local metastatic disease 2 years after focal HIFU. Adverse events (AE) were low with 70% of patients remaining with sufficient erectile function for intercourse and 97% reporting full maintenance of urinary continence. CONCLUSION: HIFU treatment in carefully selected patients is feasible. However, HIFU was oncologically not as safe as expected because of progression rates of 37.93% and risk of progression towards metastatic disease. Thus, we stopped usage of HIFU in our department.

Negative multiparametric magnetic resonance imaging for prostate cancer: further outcome and consequences.

PURPOSE: EAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI. METHODS: A total of 216 patients from 2018 to 2020 with suspicion of PCa and negative mpMRI (PI-RADS ≤ 2) were interviewed by telephone about outcome and further follow-up. Clinically significant PCa (csPCa) was defined as ISUP ≥ 2. Patients with vs. without biopsy and with vs. without PCa were compared. Univariate and multivariate analyses were performed to evaluate predictors of PCa occurrence in patients with negative mpMRI. RESULTS: 15.7% and 5.1% of patients with PI-RADS ≤ 2 on mpMRI showed PCa and csPCa, respectively. PCa patients had higher PSAD (0.14 vs. 0.09 ng/ml2; p = 0.001) and lower prostate volume (50.5 vs. 74.0 ml; p = 0.003). Patients without biopsy (25%) after MRI were older (69 vs. 65.5 years; p = 0.027), showed lower PSA (5.7 vs. 6.73 ng/ml; p = 0.033) and lower PSA density (0.09 vs. 0.1 ng/ml2; p = 0.027). Multivariate analysis revealed age (OR 1.09 [1.02-1.16]; p = 0.011), prostate volume (OR 0.982 [0.065; 0.997]; p = 0.027), total PSA level (OR 1.22 [1.01-1.47], p = 0.033), free PSA (OR 0.431 [0.177; 0.927]; p = 0.049) and no PI-RADS lesion vs PI-RADS 1-2 lesion (OR 0.38 [0.15-0.91], p = 0.032.) as predictive factors for the endpoint presence of PCa. CONCLUSIONS: Biopsy for selected patient groups (higher age, prostate volume and free PSA as well as lower PSA-Density) with negative mpMRI can be avoided, if sufficient follow-up care is guaranteed. Detailed counseling regarding residual risk for undetected prostate cancer should be mandatory.

Conditional Recurrence-Free Survival after Oncologic Extended Resection for Gallbladder Cancer: An International Multicenter Analysis.

BACKGROUND: Data to guide surveillance following oncologic extended resection (OER) for gallbladder cancer (GBC) are lacking. Conditional recurrence-free survival (C-RFS) can inform surveillance. We aimed to estimate C-RFS and identify factors affecting conditional RFS after OER for GBC. PATIENTS AND METHODS: Patients with ≥ T1b GBC who underwent curative-intent surgery in 2000-2018 at four countries were identified. Risk factors for recurrence and RFS were evaluated at initial resection in all patients and at 12 and 24 months after resection in patients remaining recurrence-free. RESULTS: Of the 1071 patients who underwent OER, 484 met the inclusion criteria; 290 (60%) were recurrence-free at 12 months, and 199 (41%) were recurrence-free at 24 months. Median follow-up was 24.5 months for all patients and 47.21 months in survivors at analysis. Five-year RFS rates were 47% for the overall population, 71% for patients recurrence-free at 12 months, and 87% for the patients without recurrence at 24 months. In the entire cohort, the risk of recurrence peaked at 8 months. T3-T4 disease was independently associated with recurrence in all groups: entire cohort [hazard ratio (HR) 2.16, 95% confidence interval (CI) 1.49-3.13, P < 0.001], 12-month recurrence-free (HR 3.42, 95% CI 1.88-6.23, P < 0.001), and 24-month recurrence-free (HR 2.71, 95% CI 1.11-6.62, P = 0.029). Of the 125 patients without these risk factors, only 2 had recurrence after 36 months. CONCLUSION: C-RFS improves over time, and only T3-T4 disease remains a risk factor for recurrence at 24 months after OER for GBC. For all recurrence-free survivors after 36 months, the probability of recurrence is similar regardless of T category or disease stage.

Challenges and perspectives in use of artificial intelligence to support treatment recommendations in clinical oncology.

Artificial intelligence (AI) promises to be the next revolutionary step in modern society. Yet, its role in all fields of industry and science need to be determined. One very promising field is represented by AI-based decision-making tools in clinical oncology leading to more comprehensive, personalized therapy approaches. In this review, the authors provide an overview on all relevant technical applications of AI in oncology, which are required to understand the future challenges and realistic perspectives for decision-making tools. In recent years, various applications of AI in medicine have been developed focusing on the analysis of radiological and pathological images. AI applications encompass large amounts of complex data supporting clinical decision-making and reducing errors by objectively quantifying all aspects of the data collected. In clinical oncology, almost all patients receive a treatment recommendation in a multidisciplinary cancer conference at the beginning and during their treatment periods. These highly complex decisions are based on a large amount of information (of the patients and of the various treatment options), which need to be analyzed and correctly classified in a short time. In this review, the authors describe the technical and medical requirements of AI to address these scientific challenges in a multidisciplinary manner. Major challenges in the use of AI in oncology and decision-making tools are data security, data representation, and explainability of AI-based outcome predictions, in particular for decision-making processes in multidisciplinary cancer conferences. Finally, limitations and potential solutions are described and compared for current and future research attempts.

[Urinary incontinence after radical prostatectomy for prostate cancer-data from 17,149 patients from 125 certified centers]. / Harninkontinenz nach radikaler Prostatektomie beim Prostatakarzinom ­ aktuelle Daten von 17.149 Patienten aus 125 zertifizierten Zentren.

BACKGROUND: In addition to erectile dysfunction, urinary incontinence is the most common functional limitation after radical prostatectomy (RPE) for prostate cancer (PCa). The German S3 guideline recommends informing patients about possible effects of the therapy options, including incontinence. However, only little data on continence from routine care in German-speaking countries after RPE are currently available, which makes it difficult to inform patients. OBJECTIVE: The aim of this work is to present data on the frequency and severity of urinary incontinence after RPE from routine care. MATERIALS AND METHODS: Information from the PCO (Prostate Cancer Outcomes) study is used, which was collected between 2016 and 2022 in 125 German Cancer Society (DKG)-certified prostate cancer centers in 17,149 patients using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). Changes in the "incontinence" score before (T0) and 12 months after RPE (T1) and the proportion of patients who used pads, stratified by age and risk group, are reported. RESULTS: The average score for urinary incontinence (value range: 0-worst possible to 100-best possible) was 93 points at T0 and 73 points 12 months later. At T0, 97% of the patients did not use a pad, compared to 56% at T1. 43% of the patients who did not use a pad before surgery used at least one pad a day 12 months later, while 13% use two or more. The proportion of patients using pads differs by age and risk classification. CONCLUSION: The results provide a comprehensive insight into functional outcome 12 months after RPE and can be taken into account when informing patients.

Solitary cardiac metastasis of urothelial carcinoma of the urinary bladder with squamous cell differentiation - a rare manifestation.

We present a case of bladder cancer with a singular cardiac metastasis. A 51-year-old female patient was referred to our department for painless macrohematuria. We confirmed the diagnosis of muscle-invasive urothelial carcinoma of the urinary bladder with partial squamous cell differentiation. Computed tomography (CT) staging demonstrated a singular cardiac metastasis. Two months after receiving six cycles of chemotherapy control CT scan revealed massive tumour progression. The singular cardiac metastasis size increased to approximately two thirds of right ventricle size. Singular cardiac metastases of urothelial carcinoma are extremely rare and show rapid progression, hence introduction to therapy should not be delayed.

Understanding tumor localization in multiparametric MRI of the prostate-effectiveness of 3D printed models.

Introduction: Understanding tumor localization in multiparametric MRI (mpMRI) of the prostate is challenging for urologists but of great importance in mpMRI-fused prostate biopsy or radical prostatectomy. The aim was to evaluate the effectiveness of 3D printed models of the prostate to help urologists to locate tumors. Methods and Participants: 20 urologists from University Medical Center Mainz (Germany) were asked to plot the location of a cancer suspicious lesion (PI-RADS ≥ 4) on a total of 30 mpMRI on a prostate sector diagram. The following 3 groups (as matched triplets) were divided into: mpMRI only, mpMRI with radiological report and mpMRI with 3D printed model (scaled 1:1). Statistical analysis was performed using one-way and two-way ANOVA (with bonferroni post-test). Results: Overall, localization of the suspicious lesion was superior with the radiological report (median of max. 10 [IQR]: MRI 2 [IQR 1;5], MRI + report: 8 [6.3;9], MRI + 3D model 3 [1.3;5.8]; p < 0.001). Residents with <1 year of experience had a significantly higher detection rate using a 3D printed model [5 (5;5.8)] compared to mpMRI alone [1.5 (1;3.5)] (p < 0.05). Regarding the estimation of index lesion extension, the 3D model showed a significant benefit (mean percentage difference [95% CI]: MRI alone 234% [17.1;451.5], MRI + report 114% [78.5;149.6], MRI + 3D model 17% [-7.4;41.3] (p < 0.01). Conclusion: Urologists still need the written radiological report for a sufficient understanding of tumor localization. The effectiveness of the 3D printed model regarding tumor localization is particularly evident in young residents (<1 year) and leads to a better overall assessment of the tumor extension.

Digital informed consent for urological surgery - randomized controlled study comparing multimedia-supported vs. traditional paper-based informed consent concerning satisfaction, anxiety, information gain and time efficiency.

INTRODUCTION: Due to a lack of time and staff, informed consent (IC) in clinical practice often lacks clarity, comprehensibility and scope of information. Digital media offer great potential to enhance IC. Aim of this study is to evaluate the effectiveness of multimedia-supported compared to traditional paper-based IC. METHODS: In the randomized, controlled, three-arm DICon (Digital Informed Consent for urological surgery) study 70 patients with an indication for prostate biopsy were randomized 1:1:1 to receive traditional paper-based IC vs. multimedia-supported information before IC vs. multimedia-supported information during IC. Patient satisfaction, anxiety and information gain were measured by validated questionnaires 2 weeks and directly before the procedure and time efficiency was recorded. Statistical analysis was performed using Kruskal-Wallis and Dunn's test (one-way ANOVA) and two-way ANOVA (with bonferroni post-test). RESULTS: Multimedia information prior to the consultation saved 32.9% time compared to paper-based (5.3 min. vs. 9.5 min; p < 0.05) and 60.4% time compared to shared multimedia information (5.3 min. vs. 13.9 min.; p < 0.001), with no difference in satisfaction (62.6 vs. 62.7 vs. 68.6 of max. 80; p = 0.07), anxiety (8 vs. 8.1 vs. 7 of max. 16; p = 0.35), or information gain (6.5 vs. 5.7 vs. 6.7 of max. 10; p = 0.23). Results on satisfaction (56.6 vs. 62.6 vs. 66; p = 0.06), anxiety (7.2 vs. 7.2 vs. 6.8; p = 0.84), and information gain (7 vs. 6.4 vs. 5.9; p = 0.43) remained stable over time. CONCLUSIONS: Multimedia-supported IC prior to consultation provided improved time efficiency (33% gain) compared to traditional paper-based IC, with comparable satisfaction, anxiety and information gain. Multimedia-supported information materials should therefore be used more frequently in patient education.

Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma-Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation.

BACKGROUND: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. METHODS: All patients with aUC (05/2017-10/2021) and aRCC (01/2012-05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. RESULTS: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. CONCLUSIONS: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC.

Prediction models of incontinence and sexual function one year after radical prostatectomy based on data from 20 164 prostate cancer patients.

BACKGROUND: Incontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment decision, physicians and patients should discuss expected impairments. Therefore, this paper firstly aims to develop and validate prognostic models that predict incontinence and sexual function of PC patients one year after RP and secondly to provide an online decision making tool. METHODS: Observational cohorts of PC patients treated between July 2016 and March 2021 in Germany were used. Models to predict functional outcomes one year after RP measured by the EPIC-26 questionnaire were developed using lasso regression, 80-20 splitting of the data set and 10-fold cross validation. To assess performance, R2, RMSE, analysis of residuals and calibration-in-the-large were applied. Final models were externally temporally validated. Additionally, percentages of functional impairment (pad use for incontinence and firmness of erection for sexual score) per score decile were calculated to be used together with the prediction models. RESULTS: For model development and internal as well as external validation, samples of 11 355 and 8 809 patients were analysed. Results from the internal validation (incontinence: R2 = 0.12, RMSE = 25.40, sexual function: R2 = 0.23, RMSE = 21.44) were comparable with those of the external validation. Residual analysis and calibration-in-the-large showed good results. The prediction tool is freely accessible: https://nora-tabea.shinyapps.io/EPIC-26-Prediction/. CONCLUSION: The final models showed appropriate predictive properties and can be used together with the calculated risks for specific functional impairments. Main strengths are the large study sample (> 20 000) and the inclusion of an external validation. The models incorporate meaningful and clinically available predictors ensuring an easy implementation. All predictions are displayed together with risks of frequent impairments such as pad use or erectile dysfunction such that the developed online tool provides a detailed and informative overview for clinicians as well as patients.

Inhibition of Vascular Endothelial Growth Factor Protects against the Development of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome in Wild-Type but Not in CD39-Null Mice.

(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model. (2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma. (3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition. (4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2.

Debate: Improvements in Systemic Therapies for Liver Metastases Will Increase the Role of Locoregional Treatments.

The benefit of resection of liver metastases depends on primary diseases. Neuroendocrine tumors are associated with favorable prognosis after resection of liver metastases. Gastric cancer has worse tumor biology, and resection of gastric liver metastases should be performed in selected patients. A multidisciplinary approach is well established for colorectal liver metastases (CLMs). Resection remains the only curative treatment of CLM. Chemotherapy and molecular-targeted therapy have improved survival in unresectable metastatic colorectal cancer. Understanding of the following two strategies, conversion therapy and two-stage hepatectomy, are important to make this patient group to be candidates for curative-intent surgery.

Short- and Long-Term Outcomes of a Transdiaphragmatic Approach for Simultaneous Resection of Colorectal Liver and Lung Metastases.

BACKGROUND: Long-term outcomes for simultaneous resection of synchronous colorectal liver and lung metastases are unknown. To address this gap, we compared outcomes and costs of three strategies for such resection. METHODS: Patients who underwent resection of synchronous colorectal liver and lung metastases during 2000-2018 were grouped by surgical strategy: simultaneous resection via a transdiaphragmatic approach (transdiaphragmatic) or separate abdominal and thoracic incisions (transthoracic) and nonsimultaneous staged resection (staged). Operative and postoperative outcomes, survival, cumulative lung recurrence, and surgical costs were evaluated. RESULTS: The study included 63 patients, 29 with transdiaphragmatic, 14 with transthoracic, and 20 with staged resection. The groups had similar demographic and clinicopathologic characteristics. Lung resection-associated blood loss for the transdiaphragmatic group was similar to that for the transthoracic group (P = .165) but lower than that for the staged group (P = .006). Hospital stay was shorter for the simultaneous groups than for the staged group (P = .007). Median surgical costs were significantly higher in the staged group ($130,733, interquartile range [IQR] $91,109-$173,573) than in the transdiaphragmatic ($70,620, IQR $58,376-$86,203, P < .001) or transthoracic ($62,991, IQR $57,405-$98,862, P < .001) group but did not differ between the transdiaphragmatic and transthoracic groups (P = .786). Rates of postoperative complications, recurrence-free survival, overall survival, and cumulative lung recurrence were similar among the groups. CONCLUSIONS: Simultaneous resection of synchronous colorectal liver and lung metastases via a transdiaphragmatic approach is associated with lower blood loss, lower costs, and similar survival compared with staged resection.