To Örebro University

INTRODUCTION: A diet rich in fruits, vegetables, coffee, and tea, limited red meat, and moderate alcohol intake may reduce the risk of renal cell carcinoma (RCC). The anti-inflammatory potential of diet has been proposed as a mechanism influencing cancer risk. This study assessed the association between an anti-inflammatory diet and RCC risk.

METHODOLOGY: Data from two Swedish cohorts, the Swedish-Mammography-Cohort and the Cohort-of-Swedish-Men, were analysed. Dietary habits were assessed using a 96-item food frequency questionnaire. The Anti-Inflammatory Diet Index (AIDI), composed of 16 food groups (11 anti-inflammatory and 5 pro-inflammatory), was used to score dietary patterns. RCC cases were identified from the Swedish Cancer Register using ICD-10 codes, and Cox proportional hazards models were used to estimate hazard ratios based on AIDI quartiles.

RESULTS: Among 71,421 participants, 431 RCC cases were identified during a 19.7-year follow-up. Higher AIDI scores were associated with a lower RCC risk (HR for Q4 vs. Q1: 0.68, CI: 0.52-0.89). In sex-stratified analyses (p-for heterogeneity = 0.006), the association was stronger in among women (HR: 0.47, CI: 0.30-0.75) but less clear in among men (HR: 0.83, CI: 0.63-1.24).

CONCLUSION: These data suggest that adherence to an anti-inflammatory diet may confer a reduced risk for RCC, especially among women.

PURPOSE: To assess the accuracy of conventional MRI with T1- and T2-weighted sequences in detecting lymphatic nodal spread (N1) in intermediate- and high-risk prostate cancer (PCa) patients via morphological criteria alone, extended pelvic lymph node dissection (ePLND) was used as the reference standard.

METHODS: This prospective observational study included patients between 2009 and 2016 with intermediate- and high-risk PCa according to the D'Amico criteria and an estimated risk of N1 > 20% on the basis of the Briganti nomogram. All patients underwent MRI prior to ePLND. Interobserver analysis was conducted across three centers.

RESULTS: Ninety-nine men, mean age 67 (5.7 SD), 93% high-risk PCa patients and 39.4% with N1 disease, according to ePLND, were evaluated. The pooled sensitivity of MRI for detecting N1 was 24.6% (95% CI: 16.3-35.1), whereas the pooled specificity was 95% (95% CI: 85.3-98.8). Interobserver agreement was moderate (Fleiss' κ = 0.56). All readers failed to identify patients with high-volume N1, and the identification of those with a high number of N1 events was inconsistent across readers. The strengths of this study include the high number of N1 cases, with a median of 17 (6-40) harvested lymph nodes per participant. Limitations include the time interval between MRI and ePLND (median of 44 days) and the lack of standardized lymph node evaluation criteria, reflecting real-world clinical practice.

CONCLUSION: MRI using only T1W and T2W sequences has demonstrated limited effectiveness in lymph node staging for intermediate- and high-risk prostate cancer, even in high-volume metastatic disease. Additionally, interobserver analysis shows only moderate agreement.

Stone size and location are key factors in predicting spontaneous stone passage (SSP), but little attention has been paid to the influence of radiological signs of stone impaction (RSSI). This research aims to determine whether RSSI, alongside stone size, can predict SSP and to evaluate the consistency of ureteral wall thickness (UWT) measurements among observers. In this retrospective study, 160 patients with a single upper or middle ureteral stone on acute non-enhanced computed tomography (NCCT) were analysed. Patient data were collected from medical records. Measurements of RSSI, including UWT, ureteral diameters, and average attenuation above and below the stone, were taken on NCCT by four independent readers blind to the outcomes. The cohort consisted of 70% males with an average age of 51 +/- 15. SSP occurred in 61% of patients over 20 weeks. The median stone length was 5.7 mm (IQR: 4.5-7.3) and was significantly shorter in patients who passed their stones at short- (4.6 vs. 7.1, p < 0.001) and long-term (4.8 vs. 7.1, p < 0.001) follow-up. For stone length, the area under the receiver operating characteristic curve (AUC) for predicting SSP was 0.90 (CI 0.84-0.96) and only increased to 0.91 (CI 0.85-0.95) when adding ureteral diameters and UWT. Ureteral attenuation did not predict SSP (AUC < 0.5). Interobserver variability for UWT was moderate, with +/- 2.0 mm multi-reader limits of agreement (LOA). The results suggest that RSSI do not enhance the predictive value of stone size for SSP. UWT measurements exhibit moderate reliability with significant interobserver variability.

We aimed to externally validate five previously published predictive models (Ng score, Triple D score, S3HoCKwave score, Kim nomogram, Niwa nomogram) for shock wave lithotripsy (SWL) single-session outcomes in patients with a solitary stone in the upper ureter. The validation cohort included patients treated with SWL from September 2011 to December 2019 at our institution. Patient-related variables were retrospectively collected from the hospital records. Stone-related data including all measurements were retrieved from computed tomography prior to SWL. We estimated discrimination using area under the curve (AUC), calibration, and clinical net benefit based on decision curve analysis (DCA). A total of 384 patients with proximal ureter stones treated with SWL were included in the analysis. Median age was 55.5 years, and 282 (73%) of the sample were men. Median stone length was 8.0 mm. All models significantly predicted the SWL outcomes after one session. S3HoCKwave score, Niwa, and Kim nomograms had the highest accuracy in predicting outcomes, with AUC 0.716, 0.714 and 0.701, respectively. These three models outperformed both the Ng (AUC: 0.670) and Triple D (AUC: 0.667) scoring systems, approaching statistical significance (P = 0.05). Of all the models, the Niwa nomogram showed the strongest calibration and highest net benefit in DCA. To conclude, the models showed small differences in predictive power. The Niwa nomogram, however, demonstrated acceptable discrimination, the most accurate calibration, and the highest net benefit whilst having relatively simple design. Therefore, it could be useful for counselling patients with a solitary stone in the upper ureter.

PURPOSE: To assess the long-term risks of infectious and thromboembolic events following inguinal (ILND) and pelvic (PLND) lymph node dissection in men with penile cancer.

MATERIAL AND METHODS: A total of 364 men subjected to ILND with or without PLND for penile cancer between 2000 and 2012 were identified in the Swedish National Penile Cancer Register. Each patient was matched based on age and county of residence with six penile cancer-free men. The Swedish Cancer Register and other population-based registers were used to retrieve information on treatment and hospitalisation for selected infectious and thromboembolic events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models with multiple imputation.

RESULTS: The risk of infectious events remained increased for more than five years postoperatively in men with penile cancer compared with matched controls. The palpable nodal disease was the only predictor of these events, with risk increasing with the cN stage. The HR at one, three and five years and six months postoperatively was 8.60 (95% CI 5.16-14.34), 4.02 (95% CI 2.65-6.09) and 1.93 (95% CI 1.11-3.38), respectively. An increased risk of thromboembolic events persisted for three years postoperatively. The HR at one and three years postoperatively was 13.51 (95% CI 6.53-27.93) and 2.12 (95% CI 1.07-4.20). The results correspond well with the over-prescription of anticoagulants observed during this period. An association with bulky disease (cN3) was observed.

CONCLUSIONS: Lymph node dissection for penile cancer is associated with an increased risk of infectious and thromboembolic events. The findings of this population-based study show that the risks of these events remain increased more than five years for infectious and three years for thromboembolic events. Improved awareness of long-term complications following ILND is of importance both among patients and care givers to ensure early detection and treatment.

Objective:  Patients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort.

Materials and methods: A total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models.

Results: Age, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69-5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44-0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71-0.95, p < 0.001) than patients treated with radical nephrectomy.

Conclusions: Age, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.

OBJECTIVE: Nationwide register data provide unique opportunities for real-world assessment of complications from different surgical methods. This study aimed to assess incidence of, and predictors for, post-operative complications and to evaluate 90-day mortality  following different surgical procedures and thermal ablation for renal cell carcinoma (RCC).

MATERIAL AND METHODS: All patients undergoing surgical treatment and thermal ablation for RCC in Sweden during 2015-2019 were identified from the National Swedish Kidney Cancer Register. Frequencies and types of post-operative complications were analysed. Logistic regression models were used to identify predictors for 90-day major (Clavien-Dindo grades III-V) complications, including death.

RESULTS: The overall complication rate was 24% (1295/5505), of which 495 (8.7%) were major complications. Most complications occurred following open surgery, of which bleeding and infection were the most common. Twice as many complications were observed in patients undergoing open surgery compared to minimally invasive surgery (20% vs. 10%, P < 0.001). Statistically significant predictors for major complications irrespective of surgical category and technique were American society of anesthiologists (ASA) score, tumour diameter and serum creatinine. Separating radical and partial nephrectomy, surgical technique remained a significant risk factor for major complications. Most complications occurred within the first 20 days. The overall 90-day readmission rate was 6.2%, and 30- and 90-day mortality rates were 0.47% and 1.5%, respectively.

CONCLUSIONS: In conclusion, bleeding and infection were the most common major complications after RCC surgery. Twice as many patients undergoing open surgery suffer a major post-operative complication as compared to patients subjected to minimally invasive surgery. General predictors for major complications were ASA score, tumour size, kidney function and surgical technique.

Background: T1a renal cell carcinoma (RCC) is typically considered a curable disease, irrespective of the choice of local treatment modality.

Objective: To identify factors associated with the risk of local and distant recurrence, and overall survival (OS) in patients with primary nonmetastatic clinical T1a RCC.

Design setting and participants: A population-based nationwide register study of all 1935 patients with cT1a RCC, diagnosed during 2005-2012, identified through The National Swedish Kidney Cancer Register, was conducted.

Outcome measurements and statistical analysis: Outcome variables were recurrence (local or distant) and OS. Possible explanatory variables included tumor size, RCC type, T stage, surgical technique, age, and gender. Associations with disease recurrence and OS were evaluated by multivariable regression and Cox multivariate analyses, respectively.

Results and limitations: Among 1935 patients, 938 were treated with radical nephrectomy, 738 with partial nephrectomy, and 169 with ablative treatments, while 90 patients had no surgery. Seventy-eight (4%) patients were upstaged to pT3. Local or metastatic recurrences occurred in 145 (7.5%) patients, significantly more often after ablation (17.8%). The risk of recurrence was associated with tumor size, upstaging, and ablation. Larger tumor size, disease recurrence, and older age adversely affected OS, whereas partial nephrectomy and chromophobe RCC (chRCC) were associated with improved survival. Limitations include register design and a lack of comorbidity or performance status data.

Conclusions: Upstaging and recurrence occurred, respectively, in 4.0% and 7.5% of patients with nonmetastatic RCCs ≤4 cm. Tumor size upstaging and ablation were associated with the risk for recurrence, while tumor size and recurrence were associated with decreased OS. Patients with chRCC and partial nephrectomy had prolonged OS in a real-world setting.

Patient summary: We studied factors that may influence the risk of disease recurrence and overall survival, in a large nationwide patient cohort having nonmetastatic renal cell carcinoma ≤4 cm. Tumor size, tumor type, and treatment were associated with the risk of recurrence and overall death. Partial nephrectomy prolonged overall survival.

CD163+ M2 macrophages have been suggested to counteract tumor immunity by increasing immunosuppressive mechanisms including PD-L1 and IL-10 expression. Soluble levels of PD-L1, IL-10, and CD163 have been reported as potential biomarkers in various cancers, although the prognostic value in renal cell carcinoma (RCC) has to be further elucidated. In the present study, we measured the levels of sPD-L1, sIL-10, and sCD163 in 144 blood samples from patients with RCC. The levels were determined by using enzyme linked immunosorbent assays. Soluble PD-L1 and CD163 were detectable in 100% of the serum samples, and sCD163 in 22% of the urine samples, while only a minority of the samples had detectable sIL-10. Significantly higher serum levels of sPD-L1 and sCD163 were observed in patients with metastatic disease (p < 0.05). The results also showed that patients with high levels of sPD-L1 in serum had shorter cancer-specific survival compared with patients with low levels (p = 0.002). The results indicate that sPD-L1 most significantly reflects tumor progression in RCC.

OBJECTIVE: To examine the association between surgical waiting times (SWTs) and all-cause mortality (ACM) in non-metastatic patients with RCC, in relation to tumour stage.

PATIENTS AND METHODS: This nation-wide population-based cohort study included 9,918 M0 RCC patients registered in the National Swedish Kidney Cancer Register, between 2009 and 2021, followed-up for ACM until 9 December 2021, and having measured SWTs. The associations between primarily SWTs from date of radiological diagnosis to date of surgery (WRS) and secondarily SWTs from date of radiological diagnosis to date of treatment decision (WRT) and date of treatment decision to date of surgery (WTS), in relation to ACM, were analysed using Cox regression analysis, adjusted for clinical and demographic characteristics, stratified and unstratified according to T-stage.

RESULTS: During a mean follow-up time of 5 years (49,873 person-years), 23% (n = 2291) of the patients died. The adjusted hazard ratio (AHR) for WRS (months) for all patients was 1.03 (95% confidence interval [CI] = 1.02-1.04; p < 0.001). When subdividing WRS on T-stage, the AHRs were 1.03 (95% CI = 1.01-1.04; p < 0.001) and 1.05 (95% CI = 1.02-1.08; p = 0.003) for stages T1 and T3, respectively, while non-significant for T2 (p = 0.079) and T4 (p = 0.807). Similar results were obtained for WRT and WTS.

CONCLUSIONS: Prolonged SWTs significantly increased the risk of early overall death among patients with RCC. The increased risk of early death from any cause show the importance of shortening SWTs in clinical work of patients with this malignant disease.