Location of Retroperitoneal Lymph Node Metastases in Upper Tract Urothelial Carcinoma: Results from a Prospective Lymph Node Mapping Study.

Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC). Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND). Design setting and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node-positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates. Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used. Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates. Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited. Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.

Urodrill - a novel MRI-guided endoscopic biopsy technique to sample and molecularly classify muscle-invasive bladder cancer without fractionating the specimen during transurethral resection.

The current diagnostic pathway for patients with muscle-invasive bladder cancer (MIBC), which involves with computed tomography urography, cystoscopy, and transurethral resection of the bladder (TURB) to histologically confirm MIBC, delays definitive treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) has been suggested for MIBC identification using magnetic resonance imaging (MRI), but a recent randomized trial reported misclassification in one-third of patients. We investigated a new endoscopic biopsy device (Urodrill) for histological confirmation of MIBC and assessment of molecular subtype by gene expression in patients with VI-RADS 4 and 5 lesions on MRI. In ten patients, Urodrill biopsies were guided by MR images to the muscle-invasive portion of the tumor via a flexible cystoscope under general anesthesia. During the same session, conventional TURB was subsequently performed. A Urodrill sample was successfully obtained in nine of ten patients. MIBC was verified in six of nine patients, and seven of nine samples contained detrusor muscle. In seven of eight patients for whom a Urodrill biopsy sample was subjected to RNA sequencing, single-sample molecular classification according to the Lund taxonomy was feasible. No complications related to the biopsy device occurred. A randomized trial comparing this new diagnostic pathway for patients with VI-RADS 4 and 5 lesions and the current standard (TURB) is warranted. Patient summary: We report on a novel biopsy device for patients with muscle-invasive bladder cancer that facilitates histology analysis and molecular characterization of tumor samples.

Urosymphyseal fistula after pelvic radiotherapy in a tertial referral centre - a rare entity with significant comorbidity requiring multidisciplinary management.

OBJECTIVE: To report population-based clinical presentation and outcomes in patients with urosymphyseal fistula (USF) after pelvic radiotherapy (RT). PATIENTS AND METHODS: A retrospective chart review was performed in 33 consecutive patients diagnosed with suspicion of USF in a tertial referral center from 2014-2022 to ascertain information about diagnostic delay, clinical presentation, precipitating causes, treatments received and outcomes during the median 22 months follow-up. Out of 33 consecutive patients with suspicion of USF, one female with vesicovaginal fistula, one patient developing RT-associated bladder angiosarcoma, four patients with short follow-up (<3 months), and three patients that during chart review not were considered to have a USF were excluded. RESULTS: In all, 24 males with a median age of 77 years were diagnosed with USF. Local pain was the predominating symptom in 17/24 (71%) patients. Endourologic manipulations preceded the diagnosis of USF in 16 patients. Five patients had a diagnostic delay of more than 3 months. At diagnosis, 20/24 patients had radiological signs of osteomyelitis, and five had a concomitant rectourethral fistula. Due to comorbidity, five patients were not amenable to any other interventions than urinary catheter or suprapubic tube in conjunction with long-term antibiotics, of which three died from infections related to the USF. Out of the remaining 19 patients receiving some form of urinary diversion, five had recurrent osteomyelitis, of which four did not undergo cystectomy in conjunction with surgery for the USF. CONCLUSIONS: Urethral endourologic interventions in patients previously subjected to pelvic RT should be performed cautiously.

Anorectal dysfunction after radical cystectomy for bladder cancer.

Objective: To prospectively assess anorectal dysfunction using patient-reported outcomes using validated questionnaires, manovolumetry and endoanal ultrasound before and 12 months after RC.Patients and methods: From 2014 to 2019, we prospectively included 44 patients scheduled for RC. Preoperatively and 12 months after surgery, 41 patients filled in a low anterior resection syndrome score (LARS-score) to assess fecal incontinence, increased frequency, urgency and emptying difficulties and a St Mark's score to assess fecal incontinence in conjunction with manovolumetry and endoanal ultrasound examinations. Pre- and postoperative patient-reported anorectal dysfunction were assessed by LARS-score and St Marks's score. At the same time-points, anorectal function was evaluated by measuring mean anal resting and maximal squeeze pressures, volumes and pressures at first desire, urgency to defecate and maximum toleration during manovolumetry. Wilcoxon's signed rank test was used to compare pre- and postoperative outcomes by questionnaires.Results: Postoperatively 6/41 (15%) patients reported flatus incontinence assessed by the LARS-questionnaire, and correspondingly the St Mark's score increased postoperatively. The median anal resting pressure decreased from 57 mmHg preoperatively to 46 mmHg after RC, but without any postoperative anatomic defects detected by endoanal ultrasound. Volumes and pressures at first desire, urgency to defecate and maximum toleration during manovolumetry all increased after RC, indicating decreased postoperative rectal sensation, as rectal compliance was unaltered.Conclusions: Postoperative flatus incontinence is reported by one out of seven patients after RC, which corresponds to decreased anal resting pressures. The finding of decreased rectal sensation might also contribute to patient-reported symptoms and anorectal dysfunction after RC.

Complete metabolic response with [18 F]fluorodeoxyglucose-positron emission tomography/computed tomography predicts survival following induction chemotherapy and radical cystectomy in clinically lymph node positive bladder cancer.

OBJECTIVE: To determine whether repeated [18 F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET-CT) scans can predict increased cancer-specific survival (CSS) after induction chemotherapy followed by radical cystectomy (RC). PATIENTS AND METHODS: Between 2007 and 2018, 86 patients with clinically lymph node (LN)-positive bladder cancer (T1-T4, N1-N3, M0-M1a) were included and underwent a repeated FDG-PET-CT during cisplatin-based induction chemotherapy. The 71 patients that had a response to chemotherapy underwent RC. Response to chemotherapy was evaluated in LNs through repeated FDG-PET-CT and stratified as partial response or complete response using three different methods: maximum standardised uptake value (SUVmax ), adapted Deauville criteria, and total lesion glycolysis (TLG). Progression-free survival (PFS) and CSS were analysed for all three methods by Cox regression analysis. RESULTS: After a median follow-up of 40 months, 15 of the 71 patients who underwent RC had died from bladder cancer. Using SUVmax and the adapted Deauville criteria, multivariable Cox regression analyses adjusting for age, clinical tumour stage and LN stage showed that complete response was associated with increased PFS (hazard ratio [HR] 3.42, 95% confidence interval [CI] 1.20-9.77) and CSS (HR 3.30, 95% CI 1.02-10.65). Using TLG, a complete response was also associated with increased PFS (HR 5.17, 95% CI 1.90-14.04) and CSS (HR 6.32, 95% CI 2.06-19.41). CONCLUSIONS: Complete metabolic response with FDG-PET-CT predicts survival after induction chemotherapy followed by RC in patients with LN-positive bladder cancer and comprises a novel tool in evaluating response to chemotherapy before surgery. This strategy has the potential to tailor treatment in individual patients by identifying significant response to chemotherapy, which motivates the administration of a full course of induction chemotherapy with a higher threshold for suspending treatment due to toxicity and side-effects.

Preventing Parastomal Hernia After Ileal Conduit by the Use of a Prophylactic Mesh: A Randomised Study.

BACKGROUND: Parastomal hernia (PSH) after urinary diversion with ileal conduit is frequently a clinical problem. OBJECTIVE: To investigate whether a prophylactic lightweight mesh in the sublay position can reduce the cumulative incidence of PSH after open cystectomy with ileal conduit. DESIGN, SETTING, AND PARTICIPANTS: From 2012 to 2017, we randomised 242 patients 1:1 to conventional stoma construction (n = 124) or prophylactic mesh (n = 118) at three Swedish hospitals (ISRCTN 95093825). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was clinical PSH, and secondary endpoints were radiological PSH assessed in prone position with the stoma in the centre of a ring, parastomal bulging, and complications from the mesh. RESULTS AND LIMITATIONS: Within 24 mo, 20/89 (23%) patients in the control arm and 10/92 (11%) in the intervention arm had developed a clinical PSH (p = 0.06) after a median follow-up of 3 yr, corresponding to a hazard ratio of 0.45 (confidence interval 0.24-0.86, p = 0.02) in the intervention arm. The proportions of radiological PSHs within 24 mo were 22/89 (25%) and 17/92 (19%) in the two study arms. During follow-up, five patients in the control arm and two in the intervention arm were operated for PSH. The median operating time was 50 min longer in patients receiving a mesh. No differences were noted in proportions of Clavien-Dindo complications at 90 d postoperatively or in complications related to the mesh during follow-up. CONCLUSIONS: Prophylactic implantation of a lightweight mesh in the sublay position decreases the risk of PSH when constructing an ileal conduit without increasing the risk of complications related to the mesh. The median surgical time is prolonged by mesh implantation. PATIENT SUMMARY: In this randomised report, we looked at the risk of parastomal hernia after cystectomy and urinary diversion with ileal conduit with or without the use of a prophylactic mesh. We conclude that such a prophylactic measure decreased the occurrence of parastomal hernias, with only a slight increase in operating time and no added risk of complications related to the mesh.

Who should record surgical complications? Results from a third-party assessment of complications after radical cystectomy.

Objective: In Sweden complications after radical cystectomy have been reported to the nationwide population-based Swedish Cystectomy Registry since 2011. Here, validation of the reporting was assessed in two healthcare regions.Materials and methods: Complications were ascertained from patient records by a third party not involved in the care delivered to 429 randomly selected patients from 949 who had undergone radical cystectomy since 2011 in four hospitals. Without knowledge of the outcome in the primary registration, post-operative complications within 90 days post-operatively were assessed by an independent review of patient charts, and the results were compared with the primary reports in the Swedish Cystectomy Registry.Results: The third-party assessment identified post-operative complications in 310 patients (72%). Low-grade complications (Clavien-Dindo I-II) were noted in 110 (26%) of the patients in the primary registration, but increased to 182 (42%) in the validation (p < 0.00001). High-grade complications (Clavien-Dindo III-V) were reported in 113 (26%) patients in the primary registration, but in 128 (30%) of the patients in the validation (p = 0.02). According to the third-party assessment, 18 patients (4%) had Clavien-Dindo grade IV complications and 12 (3%) died within 90 days of surgery (Clavien-Dindo grade V); corresponding values in the primary registration were 15 (3%) and 9 (2%), respectively. The readmission rate within 90 days increased from 27 to 32% in the validation (p < 0.00001).Conclusions: Compared with registry data, third-party assessment revealed more complications and readmissions after radical cystectomy. Hence such evaluation may improve the validity of reported complication data.

Reducing recurrence in non-muscle-invasive bladder cancer by systematically implementing guideline-based recommendations: effect of a prospective intervention in primary bladder cancer patients.

Objective: In non-muscle-invasive bladder cancer (NMIBC), local recurrence after transurethral resection of the bladder (TURB) is common. Outcomes vary between urological centres, partly due to the sub-optimal surgical technique and insufficient application of measures recommended in the guidelines. This study evaluated early recurrence rates after primary TURB for NMIBC before and after introducing a standardized treatment protocol. Methods: Medical records of all patients undergoing primary TURB for NMIBC in 2010 at Skåne University Hospital, Malmö, Sweden, were reviewed. A new treatment protocol for NMIBC was defined and introduced in 2013, and results documented during the first year thereafter were compared with those recorded in 2010 prior to the intervention. The primary endpoint was early recurrence at first control cystoscopy. Comparisons were made by Chi-square analysis and Fisher's exact test. Recurrence-free survival (RFS) in the two cohorts was also investigated. Results: TURB was performed on 116 and 159 patients before and after the intervention, respectively. The early recurrence rate decreased from 22% to 9.6% (p = 0.005) at the first control cystoscopy after treatment. Residual/Recurrent tumour at the first control cystoscopy after the primary TURB (i.e. at second-look resection or first control cystoscopy) decreased from 31% to 20% (p = 0.038). The proportion of specimens containing muscle in T1 tumours increased from 55% to 94% (p < 0.001). RFS was improved in the intervention group (HR = 0.65, CI = 0.43-1.0; p = 0.05). Conclusions: Introduction of a standardized protocol and reducing the number of surgeons for primary treatment of NMIBC decreased the early recurrence rate from 22% to 9.6% and lowered the recurrence incidence by 35%.

Vitamin D, PTH, and calcium in relation to survival following prostate cancer.

PURPOSE: Epidemiological studies suggest that low levels of vitamin D constitute a risk factor for prostate cancer. However, the results are conflicting, perhaps because prostate cancer is a very heterogeneous disease. More recent studies have focused on cancer progression and mortality. Vitamin D is closely related to both calcium metabolism and parathyroid hormone (PTH) levels, and all three factors have been implicated in prostate cancer. METHODS: We examined the associations between pre-diagnostic serum levels of vitamin D (25OHD), PTH, and calcium and mortality among 943 participants within the Malmö Diet and Cancer Study, who were diagnosed with prostate cancer. The mean time from diagnosis until the end of followup was 9.1 years (SD 4.5), and the mean time from inclusion until end of follow-up was 16.6 years (SD 4.9). The analytes were divided into quartiles, and the risk of death from prostate cancer was analyzed using Cox proportional hazard analysis, yielding hazards ratios (HR) with 95 % confidence intervals. The models were adjusted for season and year of inclusion, age at baseline, age at diagnosis, body mass index (BMI), and tumor characteristics (TNM and Gleason score). RESULTS: We observed a trend toward a lower prostate-specific mortality with 25OHD >85 nmol/L in the unadjusted analysis. This became statistically significantly in the third quartile of 25OHD (85-102 nmol/L) compared to the first (<68 nmol/L), HR 0.54 (0.34-0.85) when adjusting for age, time of inclusion, and BMI. The association was further strengthened when adjusted for age at diagnosis, Gleason score, and TNM classification with a HR in Q3 0.36 (0.22-0.60). p for trend was 0.03. Regarding calcium, there was a significantly lower HR for the second quartile (2.35-2.39 mmol/L) compared to the first (≤2.34 mmol/L) with a HR of 0.54 (0.32-0.86) in the unadjusted analysis. However, this association disappeared when adjusting for tumor characteristics. There were no associations between levels of PTH and prostate cancer mortality. CONCLUSION: This study shows that levels of pre-diagnostic vitamin D above 85 nmol/L may improve survival in men with prostate cancer.

Vitamin D, PTH, and calcium and tumor aggressiveness in prostate cancer: a prospective nested case-control study.

PURPOSE: Epidemiological studies suggest that low levels of vitamin D (25OHD) constitute a risk factor for more aggressive prostate cancer. We examined the relationship between pre-diagnostic serum levels of vitamin D, parathyroid hormone (PTH), and calcium and risk of prostate cancer according to tumor aggressiveness. METHODS: We performed a nested case-control study within the Malmö Diet and Cancer Study on 943 incident prostate cancer cases. Tumor aggressiveness was defined by Gleason score, TNM stage, and serum levels of total prostate-specific antigen. Odds ratios (OR) were calculated for different quartiles of serum levels of 25OHD, PTH, and calcium, and for interactions between them. RESULTS: We found no significant association when comparing aggressive to non-aggressive disease regarding vitamin D, PTH, or calcium. There was a trend toward an increased risk in low-grade tumors, i.e., Gleason score ≤6, and a significant association regarding Gleason score 7 tumors with OR 1.70 (1.09-2.65) in the highest quartile of vitamin D. Stratifying the analysis yielded several significant findings demonstrating a nonspecific interaction between the metabolites. In men with PTH above median, the risk of aggressive prostate cancer was double in the highest vitamin D quartile, OR 2.01 (1.24-3.25), and for non-aggressive cancer 1.82 (1.25-2.66). There was an inverse effect on risk of prostate cancer in men with PTH above median and vitamin D ≤50 nmol/L, OR 0.25 (0.09-0.71) and calcium ≤2.37 mmol/L, OR 0.53 (0.34-0.82) for aggressive cancer. CONCLUSIONS: This study showed no significant association when comparing aggressive to non-aggressive disease. There was a possible relationship between vitamin D and low-risk tumors. There were both positive and negative interactions between PTH, calcium, and vitamin D and risk of prostate cancer. These results were similar for low-risk and aggressive cases.

Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case-control study.

OBJECTIVE: To examine the risk of prostate cancer in relation to pre-diagnostic serum levels of vitamin D (25OHD(2) and 25OHD(3)), PTH, and calcium. METHODS: Nine hundred forty-three incident prostate cancer cases were identified in the Malmö Diet and Cancer Study cohort, and each was matched with one control using incidence density matching with age as the underlying timescale. We also matched for calendar time and age at inclusion. Logistic regression analysis yielded odds ratios with 95 % confidence intervals for different quartiles and deciles. All analyses were repeated stratified for age and body mass index (BMI). RESULTS: We found a weak trend toward increasing prostate cancer risk with rising vitamin D levels (p-trend across quartiles, 0.048). Dividing the cohort into deciles showed a nonlinear association. Compared to decile one, the prostate cancer risk was highest in deciles seven and eight, which corresponded to vitamin D levels of 91-97 nmol/L (1.68; 1.06-2.68), and 98-106 nmol/L (1.80; 1.13-2.85). In the other deciles, there was no association between prostate cancer risk and vitamin D levels. Albumin-adjusted calcium was positively associated with an increased risk for prostate cancer among men aged 55-65 with a BMI <25 (2.07; 1.08-3.97). No association was observed between pre-diagnostic PTH and subsequent prostate cancer incidence, and the stratified analyses revealed no other convincing relationships. CONCLUSIONS: This study suggests a possible weak positive nonlinear association between vitamin D and the risk of prostate cancer.