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Localized lymphedema of the genital region is a rare medical condition. It is named primary lymphedema if caused by a congenital malformation of the lymphatic system. Secondary lymphedemas might be induced by exogenous damage to lymphatic vessels as a result of surgical interventions, obesity, filariasis, radiotherapy or malignancy. We report a case of localized lymphedema of the genial region for which a previously unknown urothelial carcinoma turned out to be the underlying cause., (© 2024. The Author(s).)

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes., (© 2024. The Author(s).)

Patients with advanced cancer can develop symptomatic hypoglycemia at the end of life which can be associated with significant distress. We report the case of a man with metastatic urothelial carcinoma who developed acute-onset, recurrent, and symptomatic hypoglycemia concerning for non-islet cell tumor hypoglycemia (NICTH). Hypoglycemic episodes were physically and emotionally distressing and refractory to glucose tablets and a low concentration of dextrose infusion. Based on symptom burden and goals of care, treatment was escalated to a concentrated dextrose infusion requiring a central venous line, oral corticosteroids, and subcutaneous somatotropin. He was transferred to the inpatient palliative service, and on this treatment regimen, did not have additional distressing hypoglycemia. For patients with metastatic cancer and symptomatic hypoglycemia, applying a palliative-based framework with discussion of prognosis, values, and goals will lead to goal-concordant care at the end of life that can include aggressive maintenance of euglycemia to relieve suffering.

Metastatic urothelial carcinoma is a rare cause of pleural effusions. We report a case of urothelial carcinoma of the upper urinary tract in an oldest-old male patient, a smoker, with situs inversus totalis, that presented uniquely with malignant pleural effusion at presentation without evidence of a primary tumor on imaging. Cytological smears of the massive left pleural effusion revealed epithelioid neoplastic cells arranged in short cords, small-to-large clusters, and raspberry-like morules, mimicking mesothelioma; cell block preparations highlighted the presence of tubules and nest-like structures. The tumor cells showed a high nuclear-to-cytoplasmic ratio, nuclear grooves, and mitotic figures. Cytomorphologic features coupled with the immunophenotype of neoplastic cells (p63, GATA3, and uroplakin II positive) allowed the diagnosis of metastatic urothelial carcinoma and a possible nested subtype. These findings were supported by a total body computed tomography (CT) showing no evidence of a mass in the bladder or elsewhere in the urinary tract but a concentric parietal thickening of the proximal left ureter, suggesting malignancy. To our knowledge, a malignant effusion as a primary manifestation of urothelial carcinoma with nest-like features originating in the upper urinary tract has never been described previously. Our case focuses on the value of cell block in the working-up of neoplastic effusions by revealing the architectural pattern of an uncommon malignancy and the correlation between cytopathology and imaging gross findings to reach an accurate diagnosis., (© 2024 Wiley Periodicals LLC.)

Background: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC)., Materials and Methods: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm 2 /m 2 in men; PMI < 3.3 cm 2 /m 2 in women) and both hematological toxicity and tumor response., Results: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028-8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3-4 hematological toxicity between patients with sarcopenia and those without sarcopenia., Conclusions: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3-4 hematological toxicity., (© 2024. The Author(s).)

Background: The aim of this work was to evaluate the prognostic potential of preoperative thrombocytosis for recurrence-free survival (RFS) and cancer-specific survival (CSS) among patients subjected to radical nephroureterectomy (RNU) due to UTUC., Patients and Methods: Analytical cohort was composed of a single-center series of 405 patients treated between January 1999 and December 2020. Thrombocytosis was defined as a platelet count exceeding the threshold value of 400 × 10 9 per L. Along with the Kaplan-Meier survival probability, Cox proportional hazard regression models were used., Results: Preoperative thrombocytosis confirmed in 71 patients (17.5%) was significantly associated with the higher pathological tumor stage, lymph node metastasis, prior bladder cancer diagnosis, and preoperative anemia. With a median post-surgical follow-up period of 33.5 months, 125 patients (30.9%) experienced disease recurrence. The recurrence rate among patients with normal platelet levels was 13.6%, compared with 22.2% in those with preoperative thrombocytosis (p < 0.03). The 5-year RFS estimates reached 36.6% in the thrombocytosis-confirmed group. Multivariate analysis implied that preoperative thrombocytosis was a significant independent prognosticator of both poor RFS (HR 2.22, 95% CI 1.14-4.31, p = 0.02) and CSS (HR 2.48, 95% CI 1.14-3.09, p = 0.01)., Conclusions: Patients with a clinically significant elevation of platelet count prior to RNU were more likely to have UTUC with advanced tumor stages and lymph node metastases. Preoperative thrombocytosis was an independent predictor of RFS and CSS in patients who underwent radical nephroureterectomy. Furthermore, preoperative thrombocytosis may complement and refine UTUC clinical prediction algorithms as an independent indicator of adverse survival outcomes., (© 2024. Society of Surgical Oncology.)

Paraneoplastic neurological syndromes (PNS) are rare neurological disorders arising from malignancy-triggered autoimmunity, yet their association with urothelial carcinoma remains unclear. This systematic review intends to explore any connection, alongside patient/clinical features and management. A literature search identified 25 cases of bladder and upper tract carcinoma linked to PNS. Overall, while infrequent, a meaningful association between PNS and urothelial carcinoma was found in that 84% of cases met a 'possible'-or-'higher-likelihood' PNS diagnosis. Most cases presented with high-risk PNS phenotypes, predominantly cerebellar syndromes and encephalomyelitis/sensory neuronopathy, ∼17 months within cancer diagnosis/recurrence. Review findings suggest a female preponderance in suspected PNS despite higher male incidence of urothelial cancer. Main treatments consisted of surgery alongside chemotherapy or immunotherapeutics (IVIG and/or corticosteroids), which improved symptoms for a slight majority (60%). Ultimately, while common PNS-associated neoplasms should always first be excluded in suspected PNS, in the absence of alternative causes, urothelial carcinomas do merit clinical consideration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: Venous thromboembolism (VTE) is a significant predictor of worse postoperative morbidity in cancer surgeries. No data have been available for patients with preoperative VTE and upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Our aim was to assess the impact of a preoperative VTE diagnosis on perioperative outcomes in the RNU context., Methods: Patients aged 18 yr or older with a UTUC diagnosis undergoing RNU were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of VTE prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism [PE] and/or deep venous thrombosis [DVT]) was examined., Key Findings and Limitations: Within the investigated cohort of 6922 patients, history of any VTE preceding RNU was reported in 568 (8.21%) cases, including DVT (n = 290, 51.06%), PE (n = 169, 29.75%), and superficial VTE (n = 109, 19.19%). The history of VTE before RNU was predictive of higher rates of complications, the most prevalent being respiratory complications (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.43-2.22). Preoperative VTE was found to be associated with an increased risk of VTE following RNU (OR: 14.3, 95% CI: 11.48-17.82), higher rehospitalization rates (OR: 1.26, 95% CI 1.01-1.56) other than home discharge status (OR: 1.44, 95% CI: 1.18-1.77), and higher costs (OR 1.42, 95% CI: 1.20-1.68). Limitations include the retrospective nature and the use of an insurance database that relies on accurate coding and does not include information such as pathologic staging., Conclusions and Clinical Implications: The presented findings will contribute to the counseling process for patients. These patients may benefit from enhanced pre/postoperative anticoagulation. More research is needed before the following results can be used in the clinical setting., Patient Summary: Patients aged 18 yr or older with an upper tract urothelial carcinoma (UTUC) diagnosis undergoing radical nephroureterectomy (RNU) were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of venous thromboembolism (VTE) prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism and/or deep venous thrombosis) was examined. The presented findings will contribute to the counseling of patients with UTUC and preoperative VTE., (Published by Elsevier B.V.)

Background: Bladder diverticula are herniations of bladder urothelium and mucosa through the muscularis propria. The reported incidence of neoplasia arising in bladder diverticula is widely variable. The authors' objective was to study the characteristics and sensitivity of urine cytology in these patients with emphasis on primary intradiverticular bladder cancer (IDBC)., Methods: A 17-year, retrospective review of all resected bladder diverticula associated with bladder carcinoma was performed. Cases that had complete diverticular resections and preresection urine samples were included in this study. The cases were divided into either primary IDBC or primary extradiverticular bladder cancer (EDBC). Demographic data and urine cytology characteristics were recorded, and sensitivity was calculated. For IDBC, a comparison between voided and cystoscopic urines was done for cases that had both collection methods performed., Results: Of 70 patients with IDBC, 47 patients had urine cytology results that were either positive for high grade-urothelial carcinoma (HG-UC) or suspicious for HG-UC. The sensitivity for HG-UC in IDBC samples was 80%, compared with 82% in EDBC samples (p > .05). Also, 28 patients in the IDBC group had both voided and cystoscopic urine samples for comparisons; in seven patients, the voided urine sample yielded a more definitive diagnosis; in 10 patients, the cystoscopic urine sample yielded a more definitive diagnosis; and, in 11 patients, both samples were equally diagnostic (p > .05)., Conclusions: The characteristics and sensitivity of urine cytology in bladder diverticula were investigated in association with neoplasia, with an emphasis on primary intradiverticular bladder cancer. The results indicated that urine cytology remains a reliable screening and diagnostic test for detecting IDBC, with sensitivity similar to that for detecting EDBC, and no significant difference was noted between voided and cystoscopic samples., (© 2023 American Cancer Society.)

Objective: Tislelizumab may induce immune-related adverse events, especially adverse skin events. Early detection and timely intervention of cutaneous adverse events are crucial to improve patients' quality of life and reduce the disruption of therapeutic regimens. This study aimed to determine the clinical characteristics of cutaneous adverse reactions to tislelizumab and offer a reference for its rational clinical use., Methods: Case reports of cutaneous adverse reactions induced by tislelizumab were collected from the relevant databases (up to 31 March 2023). Patient age, sex, primary disease, medication use, occurrence of adverse skin conditions, treatment, and outcomes were recorded and descriptively analysed., Results: A total of 13 patients were enrolled, including six males and seven females, aged 55-79 years, with a median age of 75 years and a mean age of 70.92 ± 8.84 years. The original disease was lung carcinoma in none patients, cervical carcinoma in two, and urothelial carcinoma and squamous cell carcinoma in one each. The time from the initiation of medication use to the occurrence of cutaneous adverse reactions ranged from 7 to 177 days. Among the 13 patients, 10 showed improvement after drug withdrawal or symptomatic treatment. Two patients died (one died of disease progression and multiorgan failure, one died of acute coronary syndrome), and one patient's adverse skin reactions persisted without treatment., Conclusions: Tislelizumab-related cutaneous adverse reactions mostly occur after several days to months of treatment. In clinical practice, evaluation and monitoring should be strengthened. More attention should be paid to erythema and rashes, which may be signs of serious adverse skin reactions. Early detection and intervention can ensure the safe use of drugs and provide greater clinical benefits to patients.

Fungal bezoars (fungal balls) are rarely reported in the upper or lower urinary tract. They can be the cause of severe morbidities such as urinary tract obstruction, renal failure and fungaemia. Hereby, we present a rare case of a male patient who underwent transurethral resection of bladder tumour (TURBT), and during his postoperative period, he was diagnosed with bladder fungal bezoars adherent to his resection area. The fungal bezoars were covering an extended area of the right lateral bladder wall, including the right ureteric orifice and causing right urinary tract obstruction. Those findings were manifested only after a relooked cystoscopy and histological evaluation.We aim to present a rare example of fungal bezoars mimicking other pathologies in the urinary tract and review the current literature for similar documentation. We underline the necessity of follow-up examinations for urologists performing TURBT surgeries, including urinalysis, imaging modalities and cystoscopy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Balkan endemic nephropathy (BEN) is a rare progressive chronic renal disease found in residents living along the Balkan peninsula. We present a 92-year-old female who complained initially of cardio-respiratory symptoms and was found to have an acute hypoxemic respiratory failure with hypervolemia. The patient underwent computed tomography imaging and was found to have bilateral pleural effusions and moderate left-sided renal atrophy with left-sided hydronephrosis. The patient underwent diuresis for fluid overload and was treated with broad-spectrum antibiotics for hospital-acquired pneumonia. Further urological work-up revealed masses in the posterior bladder wall and left ureteropelvic junction. A biopsy of the posterior bladder wall mass confirmed high-grade papillary urothelial carcinoma. A review of the epidemiological history revealed the patient lived in Kosovo/former Yugoslavia for several decades following birth. A review of old records revealed the patient had chronic kidney disease (CKD) that was not fully explained by other causes, such as hypertension or diabetes. Given the epidemiological history, accelerated CKD, and unusual locations of urothelial carcinoma, the patient was diagnosed with BEN. Despite medical management and hemodialysis, the patient's renal function and mental status continued to deteriorate, and the decision was made to proceed with palliative care measures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Primary urothelial carcinoma in the prostate (UCP) is extremely rare and occurs most frequently in the bladder. There are only dozens of primary cases reported in the literature. Here, we describe a rare case of primary UCP and review the literature., Case Presentation: A 67-year-old widowed male, was referred to our hospital due to the frequency, and urgency of dysuria. Magnetic resonance imaging (MRI) examination revealed prostate size was about 57 mm × 50 mm × 54 mm, increased prostatic transitional zone, and surrounding of prostatic duct indicate bar isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 3); posterior of peripheral zone indicate patchy isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 5). Subsequently, the patient underwent a transrectal prostate biopsy. Histopathological and immunohistochemical (IHC) assessments showed prostatic high-grade urothelial carcinoma with benign prostatic hyperplasia. Finally, the patient underwent laparoscopic radical prostatectomy. Four months after surgery, CT plain and enhanced scan revealed thickening of the bladder wall. On further workup, cystoscopy revealed lymphoid follicular changes in the cut edge of the radical prostatectomy, and cystoscopic biopsies showed the malignant tumor., Conclusions: Prostatic urothelial carcinoma should always be considered if the patient with severe lower urinary tract symptoms or hematuria, PSA, and digital rectal examination without abnormalities, without a personal history of urothelial cancer, but contrast-enhanced MRI showed the lesion located in the prostate. As of right now, radical surgical resections remain the most effective treatment. The effectiveness of neoadjuvant or adjuvant chemotherapy is still controversial.

Background: Advanced bladder squamous cell carcinoma (aBSCC) is an uncommon form of urinary bladder malignancy when compared with the much higher urothelial carcinoma incidence. We studied the genomic alteration (GA) landscape in a series of aBSCC based on the association with human papilloma virus (HPV) to determine if differences in GA would be observed between the positive and negative groups., Methods: Using a hybrid capture-based FDA-approved CGP assay, a series of 171 aBSCC were sequenced to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. Programmed cell death ligand -1 (PD-L1) expression was determined by IHC (Dako 22C3) with negative expression when PD-L1 was 0, lower expression of positivity set at 1 to 49%, and higher expression set at ≥50% expression., Results: Overall, 11 (6.4%) of the aBSCC were found to harbor HPV sequences (10 HPV16 and 1 HPV 11). HPV+ status was identified slightly more often in women (NS) and in younger patients (P = 0.04); 2 female patients with aBSCC had a prior history of SCC including 1 anal SCC and 1 vaginal SCC. HPV+ aBSCC had fewer GA/tumor (P < 0.0001), more inactivating mutations in RB1 (P = 0.032), and fewer inactivating GA in CDKN2A (P < 0.0001), CDKN2B (P = 0.05), TERT promoter (P = 0.0004) and TP53 (P < 0.0001). GA in genes associated with urothelial carcinoma including FGFR2 and FGFR3 were similar in both HPV+ and HPV- aBSCC groups. MTAP loss (homozygous deletion) which has emerged as a biomarker for PRMT5 inhibitor-based clinical trials was not identified in any of the 11 HPV+ aBSCC cases, which was significantly lower than the 28% positive frequency of MTAP loss in the HPV- aBSCC group (P < 0.0001). MTOR and PIK3CA pathway GA were not significantly different in the 2 groups. Putative biomarkers associated with immunotherapy (IO) response, including MSI and TMB status, were also similar in the 2 groups. PD-L1 expression data was available for a subset of both HPV+ and HPV- cases and showed high frequencies of positive staining which was not different in the 2 groups., Conclusions: HPV+ aBSCC tends to occur more often in younger patients. As reported in other HPV-associated squamous cell carcinomas, HPV+ aBSCC demonstrates significantly reduced frequencies of inactivating mutations in cell cycle regulatory genes with similar GA in MTOR and PIK3CA pathways. The implication of HPV in the pathogenesis of bladder cancer remains unknown but warrants further exploration and clinical validation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Timely diagnosis of perioperative stroke is challenging, and therapeutic interventions are infrequently offered. The cortical hand syndrome is a rare stroke presentation that results from infarction of the precentral gyrus leading to variable neurologic deficits mimicking peripheral nerve injuries, with no prior reports in the perioperative setting. To raise awareness of this complication among anesthesiologists, we present a case of cortical hand syndrome in a surgical patient initially suspected to have a peripheral neuropathy., Clinical Features: A 68-yr-old male with multiple stroke risk factors underwent a nephroureterectomy under general anesthesia and thoracic epidural analgesia for urothelial carcinoma. The patient noted right-hand numbness and weakness to digits 3-5 immediately after surgery and notified his bedside nurse the following day. His symptoms were initially presumed to be a peripheral neuropathy secondary to surgical positioning. Computed tomography of the head the following day revealed an acute cortical infarct in the precentral gyrus consistent with cortical hand stroke syndrome. Subsequent neurologic consultation revealed additional subtle right-sided weakness. Further workup revealed moderate (60-80%) stenosis of the left carotid artery and he underwent a successful carotid endarterectomy one week later. His symptoms had mostly resolved six weeks later., Conclusion: Cortical hand stroke syndrome is a rare presentation of perioperative stroke that may be misdiagnosed as a peripheral neuropathy. Our case presentation highlights that perioperative stroke should be considered for patients presenting with neurologic deficits of the hand, particularly those with deficits in multiple peripheral nerve territories and stroke risk factors., (© 2023. Canadian Anesthesiologists' Society.)

Introduction: A 65-year-old female patient could no longer take oral food or medications due to a duodenal occlusion associated with metastatic urothelial carcinoma. Her pre-existing chemotherapy-induced polyneuropathy had been well treated with pregabalin orally., Methods: Since only preparations for oral use of pregabalin are available, pregabalin suppositories were compounded by the hospital pharmacy for rectal use in this patient., Results: With the rectal administration, the treatment was successfully continued; we measured a good increase in serum levels and the symptoms improved significantly., Discussion: Cancer patients often need to be treated with co-analgesics. At the end of life, treatment often cannot be continued due to lack of other than oral administration. Our case adds to the low evidence of pregabalin administered rectally., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Metastasis to the gallbladder is very rare. This case report highlights a rare cause of acute cholecystitis, which should be considered by the surgeon and other treating physicians in the differential diagnosis of patients with urothelial carcinoma., Case: We report the case of a 73 year-old man with follow-up oncology care. He was diagnosed with infiltrating urothelial carcinoma in 2019, received neoadjuvant chemotherapy, and subsequently underwent radical cystectomy with ureteroileostomy in April 2020. Histology confirmed complete regression of bladder cancer, the lymphonodes were also free of tumour infiltration. In July 2021, the patient was examined for intermittent abdominal pain, predominantly of the right upper quadrant. On clinical examination, the gallbladder hydrops was palpable and a positive Murphy's sign was present. Due to the signs of acute cholecystitis, the patient was indicated for acute cholecystectomy. Gallbladder histology revealed metastatic involvement of the gallbladder wall by urothelial carcinoma., Conclusion: If patients with bladder cancer present with intermittent right subcostal pain or signs of acute cholecystitis and diagnostic imaging shows a thickened gallbladder wall, clinicians and radiologists should consider the possibility of metastatic origin of lesion.

Purpose: About one-third of patients who undergo radical nephroureterectomy (RNUx) for upper tract urothelial carcinoma (UTUC) experience intravesical recurrence (IVR). This study investigated whether pyuria is a feasible predictor of IVR after RNUx in patients with UTUC., Materials and Methods: Seven hundred forty-three patients with UTUC who underwent RNUx at a single institute were analyzed in this study. The participants were divided into two groups: those without pyuria (non-pyuria) and those with pyuria. Kaplan-Meier survival analysis was performed, and p-values were assessed using the log-rank test. Cox regression analyses were performed to identify the independent predictors of survival., Results: The pyuria group had a shorter IVR-free survival period (p=0.009). The five-year IVR-free survival rate was 60.0% in the non-pyuria group vs. 49.7% in the pyuria group according to the Kaplan-Meier survival analysis. After the multivariate Cox regression analysis, pyuria (hazard ratio [HR]=1.368; p=0.041), a concurrent bladder tumor (HR=1.757; p=0.005), preoperative ureteroscopy (HR=1.476; p=0.013), laparoscopic surgery (HR=0.682; p=0.048), tumor multiplicity (HR=1.855; p=0.007), and a larger tumor (HR=1.041; p=0.050) were predictors of risk for IVR. There was no association between pyuria and recurrence-free survival (p=0.057) or cancer-specific survival (p=0.519) in the Kaplan-Meier survival analysis., Conclusions: This study concluded that pyuria was an independent predictor of IVR in patients with UTUC after RNUx., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Implanted ports have provided clinicians with long term venous accessibility, while maintaining comfort and convenience for their patients. One of the most commonly used implanted ports for oncological access is a Mediport (Norfork Medical, Skokie, IL). Guidelines (INS2021) strongly recommend placing central catheter tips at the cavo-atrial junction. In fact, too deep atrium position may be associated with micro-traumatism, possibly leading to a catheter associated right atrial thrombosis (CRAT). No significant literature discusses the possibility of such port masses being seeded by a bacteria, as in the case for endocarditis, which was seen in our patient. In the following case report, we will explore the case of a 41-year-old female with metastatic urothelial carcinoma who developed multiple right atrial masses possibly associated with a deeply seated totally implanted vascular access device (TIVAD) tip within the right atrial wall. These right atrial masses were of unknown origin, and in the setting of MRSA bacteremia, multiple possible etiologies would be discussed. We will also explore ways in which similar complications can be easily prevented in the future., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Perpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF., Objectives: In the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology., Methods: Patients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma-associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR., Results: The expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR., Conclusions: LncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint., Competing Interests: Funding Support and Author Disclosures This research was funded by the Atrial-Fibrillation-Innovation-Platform (AFIPonline.org), Dutch Heart Foundation (2020-2020B003, DnAFix), NWO (NWA.1389.20.157 CIRCULAR), CVON-STW2016-14728 AFFIP, NWO-Vidi (2016-91717339 to Dr de Groot), and Medical Delta. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Urothelial carcinomas (UC) account for 6 and 2% of all cancers in men and women, respectively. Human papillomavirus (HPV) is one of the causative agents in cancers of the uterine cervix and head and neck. The role of HPV is also being studied in cancers of the urinary bladder, penis, and prostate. As p16-INK4a is a surrogate marker for high-risk HPVE7 oncoprotein, this study aims to highlight the utility of p16 immunohistochemistry (IHC) in the evaluation of HPV-associated UC., Materials and Methods: A retrospective study was conducted on UC of the bladder received in the Pathology department between January 2013 and December 2018. Bladder biopsies from non-neoplastic lesions served as controls. IHC was done for the detection of the p16 antigen. The p16 staining was recorded as positive, when there was strong staining in >50% of tumor nuclei. The p16 positive and negative tumors were compared based on age, gender, tumor size, grade, and muscle invasion. P value <0.05 was considered statistically significant., Results: The expression of p16 was analyzed in 72 UC and compared with 20 non-neoplastic cases, of which 26.4% of the cases showed p16 expression. The p16 expression was absent in the non-neoplastic lesions. While the majority (87.5%) of the low-grade tumors were negative for p16 expression, 43.8% high-grade tumors were positive. Similarly, a larger proportion of invasive carcinomas (38.8%) expressed p16 as compared to non-invasive carcinomas (13.8%). Thus, p16 expression showed a significant association with grade and stage in these malignancies (P < 0.05)., Conclusion: The p16 expression was associated with high-grade and muscle-invasive UC. The p16 was absent in all non-neoplastic and precursor lesions. Thus, it can provide essential information not only about HPV association but also on the prognostic implications for the patients.

Ureteric carcinoma is the rarest of all urothelial malignancies, and little attention has been given to it. Palliation in these groups of patients is a dilemma in the clinics. Use of chemotherapeutic agents in ureteric carcinoma is a double edged sword, as these patients had already impaired renal function due to post-renal failure and nephrotoxic nature of most of the chemotherapeutic agents can further deteriorate the renal function, making the management approach, a relatively visionary task. Here, we present a case of a 77-year-old female with metastatic ureteric carcinoma locally complicated with hydroureteronephrosis, coming to us with gross haematuria, lower abdominal pain along with cough. Apart from age factor of the lady, presence of hydroureteronephrosis and pulmonary metastases was another challenge for us. Paclitaxel remains the mainstay of our treatment., Keywords: carcinoma; case reports; metastasis; paclitaxel.

Competing Interests: Competing interests: None declared.

Introduction: Preoperative hydronephrosis is closely associated with the prognosis of patients with bladder cancer. This study assesses the effect of preoperative hydronephrosis on the prognosis after radical cystectomy (RC) among patients with different pathological stages of bladder urothelial carcinoma., Methods: We retrospectively analyzed the clinical data of 231 patients who underwent RC because of bladder urothelial carcinoma at our institution from January 2013 to December 2017. The overall survival (OS) in patients with or without preoperative hydronephrosis was followed up and compared, and the prognostic role that preoperative hydronephrosis played in patients with different pathological stages of bladder cancer was analyzed. Multivariate analysis was performed with the help of Cox proportional hazards regression models, the postoperative survival was analyzed with the help of Kaplan-Meier plots and log-rank test, and the p values of multiple testing were corrected using the Bonferroni correction., Results: Of 231 patients, 96 were patients with preoperative hydronephrosis and 115 patients had died by the end of the follow-up. Survival analysis found the 3- and 5-year survival rates after radical surgery of patients with preoperative hydronephrosis were significantly lower than those of patients without preoperative hydronephrosis (p &lt; 0.001). Multivariate analysis found preoperative hydronephrosis, T stage of tumor, and lymphatic metastasis were independent influencing factors of postoperative OS (p &lt; 0.05). Survival analysis of subgroups according to pathological stages found in pT3-4N0M0 patients had a significant difference in postoperative survival between the group with preoperative hydronephrosis and the group without preoperative hydronephrosis (p &lt; 0.0001)., Conclusion: The results indicate that preoperative hydronephrosis mainly affects postoperative OS in the patients whose pathological stage of bladder cancer is pT3-4N0M0., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: To elucidate the association between adolescent microscopic hematuria and early onset urothelial carcinoma and renal cell carcinoma., Methods: Nationwide, population-based, retrospective cohort study using medical data of 970,366 adolescents aged 16 through 19 years (58.6% male) examined for fitness for military service between 1980 and 1997. Diagnoses of persistent isolated microscopic hematuria were given after thorough work up process excluding any other renal abnormalities. Incident cases of urothelial carcinoma and renal cell carcinoma diagnosed during the years of 1982-2012 were retrieved from the Israeli National Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio (HR) separately for urothelial carcinoma and renal cell carcinoma., Results: During a cumulative follow-up of 22,115,629 person-years (median follow-up, 22.8), persistent isolated microscopic hematuria was diagnosed among 5509 (0.6%) adolescents. Urothelial carcinoma and renal cell carcinoma developed in 332 (3 among those with persistent isolated microscopic hematuria) and 292 (2) individuals, respectively. The adjusted HR for incident urothelial carcinoma among adolescents with isolated microscopic hematuria was 1.17 (95% CI, 0.38-3.66) and the adjusted HR for renal cell carcinoma was 1.02 (95% CI, 0.25-4.12)., Conclusion: Persistent asymptomatic isolated microscopic hematuria at adolescence was not associated with increased risk for urothelial carcinoma nor renal cell carcinoma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: To better understand the characteristics, and survival outcomes of synchronous renal cell carcinoma (RCC) and urothelial carcinoma (UC), we described and analyzed the clinical features, factors, and prognosis of patients with synchronous RCC and UC using a large population-based database., Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified patient with concurrent RCC and UC at initial diagnosis. Their clinicopathological features and prognosis were evaluated. A logistic regression model was used to examine risk factors for the occurrence of concomitant RCC and UC, and Kaplan-Meier survival curves were used to estimate overall survival., Results: A total of 61,454 RCC patients were identified from the SEER database, 704 (1.1%) patients presented with synchronous RCC and UC. Among these patients, concurrent bladder tumors (566/704) are more common. Subsequently, subgroup analysis based on the location of UC indicated that patients with concurrent RCC and upper tract urothelial carcinoma (UTUC) had unfavorable UC characteristics (higher tumor stage and grade), compared with patients with concomitant bladder cancer. An increased risk of concurrent UC was observed among older age, male sex, and white race. Meanwhile, papillary RCC histology [odds ratio (OR) 3.23; 95% confidence interval (CI) 2.13-4.90], and smaller tumor (OR 6.63; 95% CI 4.46-9.87) were independent risk factors for concomitant UTUC. In addition, we found that synchronous RCC and UTUC was associated with worse survival by using Kaplan-Meier and multivariable analysis [hazard ratio (HR) 2.36, 95% CI 1.89-2.95]. However, concomitant bladder cancer did not affect survival outcomes of patients with RCC (HR 1.00, 95% CI 0.86-1.17)., Conclusion: We found that synchronous concurrent RCC and UC is relatively uncommon and mostly located in the bladder. Older age, male sex, and white race increase the risk of synchronous RCC and UC. Meanwhile, patients with papillary RCC histology, and smaller tumors are more likely to have concomitant RCC and UTUC. Furthermore, our findings suggest that synchronous RCC and UTUC has a worse prognosis, while, concomitant bladder tumor did not affect the oncological outcomes of RCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Liu, Wang, Wang and Li.)

Purpose of Review: To provide an overview of the recent literature on RNA-based molecular urine assays for the diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC)., Recent Findings: Articles were eligible for inclusion if performance metrics sensitivity, specificity, and negative-predictive value (NPV) were reported or could be calculated. Only prospective studies published between 2020-2022 were included. Five out of fourteen studies addressed the primary diagnostic setting; the proportion of gross hematuria patients in all study populations was >50%. Only one study reported performance metrics within a microscopic hematuria subgroup. This study evaluated Xpert Bladder and reported a sensitivity: 73%, specificity: 84%, NPV: 99%, and PPV: 12%. Ten studies assessed test performance during surveillance for NMIBC. For the detection of high-grade (HG) and high-risk (HR) NMIBC, sensitivity, specificity, NPV, and PPV varied between 78-100%, 64-89%, 97.0-99.7%, and 9.2-39%., Summary: Multiple RNA-based urine assays have been investigated for the detection of urothelial cancer in the primary or surveillance setting. However, studies included within this review have important limitations, hampering the interpretation of study results. As such, performance metrics should be interpreted with caution and further research is required to evaluate the clinical impact of RNA-based urine assays in daily practice., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the comprehensive complication index(CCI) and Clavien-Dindo classification(CDC) for short-term postoperative complications in radical cystectomy and assess cumulative surgical morbidity to compare sufficient surgical skill., Methods: From September 30, 2010, to October 1, 2020, clinical data of patients with urothelial carcinoma who underwent radical cystectomy with urinary diversion were gathered, patients who had only a urinary diversion, bladder sparing surgery, additional abdominal surgeries at the same time were all excluded. The CDC and CCI were utilized to evaluate 30-d complications after radical cystectomy and the relevance of hospital stay was compared between CCI and CDC. The cumulative sum control models (CUSUM) were used to evaluate the overall surgical morbidity of radical cystectomy in our facility and for comparisons between surgeons., Results: This study enrolled a total of 635 individuals, 548 (86.3%) of whom had 1124 problems. The incidence of severe complications (CDC≥ Grade III) was 10.2%. The average CCI was 20.2 ± 14.7. Gender, urinary diversion subtype, procedure method, and surgeon were significantly correlated with the increase of CCI (p < 0.05). The CCI demonstrated a better relationship with hospital stay (R 2  = 0.429) than the CDC (R 2  = 0.361). The CUSUM-CCI model demonstrated a difference and growth distribution in dynamic time between individual surgeons., Conclusions: CCI can better reflect the incidence of complications for radical cystectomy than CDC, and CCI is more strongly correlated with postoperative hospital stay. The CUSUM-CCI model can reflect the quality of surgical skill for each surgeon instantaneously., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a good alternative and diagnostic tool for gastrointestinal wall thickening with prior negative endoscopic biopsies., Case Presentation: Here we reported a case of a 60-years-old woman admitted with atrophic right kidney and hydronephrosis and intermittent postprandial bloating. Esophagogastroduodenoscopy and small bowel endoscopy revealed wall thickening and stenosis at the junction of the descending and inferior duodenum. Biopsies from endoscopy showed no specific findings. EUS-FNA of the thickened duodenal wall was performed and histopathological examinations revealed poorly differentiated carcinoma. Immunohistochemically staining was positive for pan-cytokeratin, CK7, CK20, and weakly positive for GATA-3 and P63. These results were highly suggestive of metastatic urothelial cancer., Conclusions: EUS-FNA played an important role in the diagnosis of unexplained gastrointestinal wall thickening and rare metastases to the gastrointestinal wall., (© 2022. The Author(s).)

Background: Autoimmune autonomic ganglionopathy is a rare, immune-mediated disorder associated with anti-ganglionic α3-subunit nicotinic acetylcholine receptor (anti-α3gAChR) antibodies, which bind to acetylcholine receptor in autonomic ganglia (parasympathetic and sympathetic) leading to autonomic failure. This disorder is mostly associated with viral infections, but it can also be associated with systemic malignancies. Here, we report the case of a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer., Method: Case report., Results: A 47-year-old man, without medical history of interest, stated to the emergency department for progressive blurry vision with eye and mouth dryness, constipation, and dizziness upon standing for the last 2 weeks. Orthostatic hypotension was demonstrated by a drop in 13.3 mmHg mean blood pressure (BP) from supine (100/60 mmHg) to 45° reclining sitting position (80/50 mmHg). Blood tests, chest X-ray, brain MRI, and electroneuronography were unremarkable. Electrochemical skin conductance was reduced. Serological examination was positive for anti-α3gAChR antibodies. A full-body CT scan revealed a bladder tumor, which was treated by transurethral bladder resection. The pathologic study demonstrated a low-grade non-muscle-invasive bladder urothelial carcinoma. After tumor resection, and treatment with intravenous immunoglobulins and corticoids, a gradually improvement was observed. Today, the patient remains asymptomatic., Conclusion: Subacute panautonomic failure can be the first symptom for systemic malignancies. This case reports a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer. This case highlights the importance of a systemic study to rule out the presence of cancer when autoimmune autonomic ganglionopathy is present., (© 2022. Fondazione Società Italiana di Neurologia.)

Aim: We aimed to explore the association between cancer cachexia phenotypes in the early phase of treatment induction and the prognosis of advanced urothelial cancer (aUC) patients receiving pembrolizumab., Methods: This retrospective study included 31 aUC patients treated with pembrolizumab as a second- or later-line therapy. Patients were categorized into three early cancer cachexia phenotypes by changes in skeletal muscle and total adipose indices calculated using computed tomography images taken immediately before and within 3 months after the initiation of pembrolizumab: No Wasting (NW, 11 patients), Fat-Only Wasting (FW, 13), and Muscle and Fat Wasting (MFW, seven). Its association with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated., Results: The median follow-up period was 5.7 months. The median number of cycles of pembrolizumab was five. The ORR in NW/FW/MFW was 86%/38%/0%, respectively (p = 0.001). The PFS and OS rates were the best in NW, followed in order by FW and MFW (PFS, 69%/45%/0% at 12 months, p = 0.008; OS, 100%/65%/0% at 12 months, p < 0.001). In multivariate analysis including posttherapeutic cachexia-associated parameters, cancer cachexia phenotype (MFW vs. FW/NW) was an independent predictor of poor OS (hazard ratio 8.59, p < 0.001) along with an increase in neutrophil-lymphocyte ratio (p = 0.028)., Conclusion: Early cancer cachexia phenotypes were significantly associated with the survival of aUC patients treated with pembrolizumab. In contrast to the very early progression and poor prognosis in the MFW group, long-term survival can be expected in the NW/FW groups., (© 2021 John Wiley & Sons Australia, Ltd.)

Context: The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria., Objective: To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR)., Evidence Acquisition: Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review., Evidence Synthesis: A total of 44 studies were included. The total number of participants was 229701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14-20%) for visible haematuria (VH) and 3.3% (95% CI 2.45-4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1-2%) for VH and 0.58% (95% CI 0.42-0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4-1.2%) for VH and 0.17% (95% CI 0.081-0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10-1.17 for VH; 1.54, 95% CI 1.34-1.78 for NVH; p < 0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24-1.61 for VH; 1.53, 95% CI 1.36-1.72 for NVH; p < 0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups., Conclusions: Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations., Patient Summary: Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

p16 (CDKN2A) is a member of the INK4 class of cell cycle inhibitors, which is often dysregulated in cancer. However, the prevalence of p16 expression in different cancer types is controversial. 15,783 samples from 124 different tumor types and 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. p16 was detectable in 5,292 (45.0%) of 11,759 interpretable tumors. Except from adenohypophysis in islets of Langerhans, p16 staining was largely absent in normal tissues. In cancer, highest positivity rates were observed in uterine cervix squamous cell carcinomas (94.4%), non-invasive papillary urothelial carcinoma, pTaG2 (100%), Merkel cell carcinoma (97.7%), and small cell carcinomas of various sites of origin (54.5%-100%). All 124 tumor categories showed at least occasional p16 immunostaining. Comparison with clinico-pathological data in 128 vulvar, 149 endometrial, 295 serous ovarian, 396 pancreatic, 1365 colorectal, 284 gastric, and 1245 urinary bladder cancers, 910 breast carcinomas, 620 clear cell renal cell carcinomas, and 414 testicular germ cell tumors revealed only few statistically significant associations. Comparison of human papilloma virus (HPV) status and p16 in 497 squamous cell carcinomas of different organs revealed HPV in 80.4% of p16 positive and in 20.6% of p16 negative cancers (p<0.0001). It is concluded, that a positive and especially strong p16 immunostaining is a feature for malignancy which may be diagnostically useful in lipomatous, urothelial and possibly other tumors. The imperfect association between p16 immunostaining and HPV infection with high variability between different sites of origin challenges the use of p16 immunohistochemistry as a surrogate for HPV positivity, except in tumors of cervix uteri and the penis., Competing Interests: The p16 antibody mouse monoclonal, clone MSVA-016R was provided by MS Validated Antibodies GmbH, Hamburg, Germany. MS Validated Antibodies GmbH is owned by a family member of GS. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Brachytherapy for prostate cancer treatment may induce secondary bladder cancer during long-term follow-ups. This study reviews the risk and tumor characteristics of secondary bladder cancer after brachytherapy., Methods: This single-institution retrospective study included 1162 patients treated with low-dose-rate permanent seed implantation brachytherapy with iodine-125, with or without external beam radiation therapy, for localized prostate cancer. We calculated and compared the rates of secondary bladder cancer among patients treated with brachytherapy and radical prostatectomy (n = 218) before and after a propensity score-matching analysis. Possible risk factors for secondary bladder cancer, such as patient age and external beam radiation therapy administration, were analyzed., Results: Of 1162 patients with a median follow-up period of 11.4 (range: 0.7-15.5) years, 26 presented with urothelial carcinomas and 1 with adenocarcinoma at a median of 8.9 (range: 2.9-14.0) years after brachytherapy, although the incidence rates of secondary bladder cancer after brachytherapy were not significantly different from those after radical prostatectomy. No significant risk factors for secondary bladder cancer were identified. The initial symptoms of secondary bladder cancer were gross hematuria (74%) and microscopic hematuria with positive urine cytology (15%). Among 26 cases of secondary urothelial carcinoma, 54% were high-grade and 46% were invasive. After brachytherapy, invasive urothelial carcinoma occurred later than noninvasive urothelial carcinoma (p = 0.01)., Conclusions: Considering the aggressive malignancy of secondary bladder cancer, cystoscopy and urine cytology should be performed for further investigation of the causes of gross or microscopic hematuria and rule out secondary bladder cancer in cases followed longer than 3 years after brachytherapy., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To report our experience of bladder urothelial cell carcinoma (UCC) in children and review contemporary management and follow-up of paediatric UCC., Patients and Methods: Between 2004 and 2020, five patients (4 boys and 1 girl) were managed at our centre for urothelial cell carcinoma of the bladder. Data was collected by note review for age at presentation, symptoms, clinical findings, investigations, treatment and follow-up., Results: All five patients presented with visible haematuria, two had dysuria and one had suprapubic pain. Bladder ultrasound scan (USS) showed exophytic bladder lesions in only 4 patients. Definitive diagnosis and treatment were achieved by cystoscopic excision. Four patients had PUNLMP while one had Grade 3 pTa UCC of the bladder which required further cystoscopic excision and intravesical Mitomycin C (MMC) instillation. All patients were followed up clinically, with renal USS and cystoscopy. We have observed recurrence of the carcinoma in two patients requiring further cystoscopic excision and intravesical MMC., Conclusion: Bladder urothelial cell carcinoma in children should be suspected in children presenting with haematuria. If renal USS is normal, cystoscopy should be considered for diagnosis and treatment. Compared to adults, children with bladder UCC often have favourable histopathology and prognosis. Close follow-up is necessary with renal USS and cystoscopy to detect recurrence even in PUNLMP., Competing Interests: Declarations of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

Objective: To assess the impact of trainee involvement in surgery on perioperative and oncological outcomes of patients undergoing radical cystectomy (RC)., Materials and Methods: We reviewed the records of patients undergoing RC for urothelial carcinoma between 2000 and 2015 at our institution. Trainee level was categorized as fellow, chief, senior and junior residents. Demographic, perioperative and oncological outcomes were recorded and compared between the groups. Specifically, operative time, 30-day complications, severe complications (Clavien III-V) and oncological outcomes (overall, cancer-specific and recurrence-free survival) were assessed., Results: A total of 895 patients were included for study. On multivariable analysis, operative times were 30-40 minutes longer in procedures assisted by junior residents as compared to more senior trainees. Notably, trainee level was not associated with overall or severe complications on multivariable analyses. Similarly, trainee level was not associated with oncologic outcomes., Conclusion: While cases assisted by junior residents had longer operative times, complication rates and oncological outcomes were comparable across trainee groups. Trainee level does not appear to have an impact on perioperative and oncological outcomes of RC for urothelial carcinoma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Bladder cancer (BC) is highly heterogeneous with regard to clinical course, etiology, histology, and geographic distribution. Recent clinical observations suggest changes in the pattern of BC in the Sudan perhaps due to lifestyle change following the massive displacement from rural to urban areas. The present study aimed to characterize the clinical profile of the BC among Sudanese patients and compare it with what has been previous reported., Material and Methods: Demographic, habitual, clinical, and histopathology information of 1610 patients with BC were obtained from the hospital record of Ibn Sina specialized hospital, Soba University hospital, Khartoum North hospital and Khartoum teaching hospital during the period 2007-2019. The data was analyzed using SPSS program version 23., Results: Of the 1610 cases of BC, 1480 cases (91.9%) were males and 130 cases (8.1%) were females. The most affected patients (39.3%) were those with age group ranging between 61-75 year-old. The vast majority of the patients (73%) were from urban and/or metropolitan areas of the capital Khartoum, whereas the remaining (27%) were farmers coming from rural areas. Although, smoking habits information were missed in 410 patients, 44% of the patients were smokers. History of hematuria was present in almost all cases (99.4%), whereas history of urinary bilharziasis was mentioned in 40.9% of the patients' records. The TCC histology type was seen in 77.4% of the cases, SCC in 21.1%, and adenocarcinoma in only 1.5% of all cases. The vast majority of the tumors were poorly differentiated tumors (700/52.6%), followed by moderately differentiated tumors (430/32.3%) and well differentiated ones (200/15.1%). Of the total tumors, 346/26% were Ta-T1, 456/34% were T2, and 528/40% were T3-T4a,b. Most of tumors were solid ones, accounting for 74% compared with the papillary ones (26%) with most (54.9%) of the tumor located in the lateral wall of the bladder. Although in 620 (38.5%) patients, the follow up information were missing from the records, still the recurrence of the tumors were recorded in 890 (55.3%) of the patients 6 month after the initial therapy., Discussion: The results showed that poorly differentiated, muscle invasive, and high recurrent TCCs tumors dominate BC profile of Sudanese patients. It revealed also that the most affected population are those between 61-75 yearold. These findings are in clear contrast with BC profile, previously, reported in which solitary muscle invasive Bilharzia-associated SCCs tumors affecting younger population was the dominated patterns as reported by Daoud el al (1968), Malik et al., (1975) and later by Sharfi et al., (1992). Thus clear change in BC profile in Sudan is evident, perhaps due to increased urbanization and style of life that led to change in the causative etiology, and eventually the histology type., Key Words: Bladder cancer, Squamous cell carcinoma, Transitional Cell Carcinoma, Post-bilharzial carcinoma.

Upper tract urothelial cancers account for 5% of all urothelial cancers. Among these, more than 90% of tumours are located in the renal pelvis, while ureteric tumours are extremely rare. The distal ureter is the most common location, although multifocal implants may also occur. Megaureter is a common cause of obstructive uropathy in neonates and children. Nevertheless, it may be unnoticed, if asymptomatic. Megaureter may be obstructing or refluxing. Long-standing urinary stasis and recurrent urinary tract infection in megaureter may cause chronic irritation of the ureteric mucosa leading to dysplasia and malignancy. We report a 55-year-old man diagnosed with bilateral obstructive megaureter with right lower ureteric urothelial cancer and review the current literature.

Objective: Epileptic seizures are a common and potentially devastating complication of metastatic brain tumors. Although tumor-related seizures have been described in previous case series, most studies have focused on primary brain tumors and have not differentiated between different types of cerebral metastases. The authors analyzed a large surgical cohort of patients with brain metastases to examine risk factors associated with preoperative and postoperative seizures and to better understand the seizure risk factors of metastatic brain tumors., Methods: Patients who underwent resection of a brain metastasis at the University of California, San Francisco (UCSF), were retrospectively reviewed. Patients included in the study were ≥ 18 years of age, required resection of a brain metastasis, and were treated at UCSF. Primary cancers included melanoma, non-small cell lung adenocarcinoma, breast adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, renal cell carcinoma, urothelial carcinoma, ovarian carcinoma, cervical squamous cell carcinoma, and endometrial adenocarcinoma. Patients were evaluated for primary cancer type and seizure occurrence, as well as need for use of antiepileptic drugs preoperatively, at time of discharge, and at 6 months postoperatively. Additionally, Engel classification scores were assigned to those patients who initially presented with seizures preoperatively. Univariate and multivariate regression analyses were used to assess the association of tumor type with preoperative seizures., Results: Data were retrospectively analyzed for 348 consecutive patients who underwent surgical treatment of brain metastases between 1998 and 2019. The cohort had a mean age of 60 years at the time of surgery and was 59% female. The mean and median follow-up durations after the date of surgery for the cohort were 22 months and 10.8 months, respectively. In univariate analysis, frontal lobe location (p = 0.05), melanoma (p = 0.02), KRAS mutation in lung carcinoma (p = 0.04), intratumoral hemorrhage (p = 0.04), and prior radiotherapy (p = 0.04) were associated with seizure presentation. Postoperative checkpoint inhibitor use (p = 0.002), prior radiotherapy (p = 0.05), older age (p = 0.002), distant CNS progression (p = 0.004), and parietal lobe tumor location (p = 0.002) were associated with seizures at 6 months postoperatively. The final multivariate model confirmed the independent effects of tumor location in the frontal lobe and presence of intratumoral hemorrhage as predictors of preoperative seizures, and checkpoint inhibitor use and parietal lobe location were identified as significant predictors of seizures at 6 months postoperatively., Conclusions: Within this surgical cohort of patients with brain metastases, seizures were seen in almost a quarter of patients preoperatively. Frontal lobe metastases and hemorrhagic tumors were associated with higher risk of preoperative seizures, whereas checkpoint inhibitor use and parietal lobe tumors appeared to be associated with seizures at 6 months postoperatively. Future research should focus on the effect of metastatic lesion-targeting therapeutic interventions on seizure control in these patients.

Introduction: To clarify the safety and efficacy of en bloc simultaneous robot-assisted radical cystectomy (RARC) and laparoscopic nephroureterectomy (LNU) for synchronous muscle-invasive bladder carcinoma and upper tract urothelial carcinoma (UTUC) or UTUC of a solitary kidney, we evaluated the perioperative and short-term outcomes of this surgical procedure compared with those of simultaneous open radical cystectomy and nephroureterectomy., Methods: We prospectively enrolled consecutive patients receiving en bloc simultaneous RARC and LNU between December 2018 and March 2020 at two institutes. Patients' characteristics, surgical, perioperative, and pathological outcomes and recurrence rate within 6 months were compared with a historical control receiving simultaneous open radical cystectomy and nephroureterectomy., Results: Ten patients receiving simultaneous RARC and LNU and 17 receiving simultaneous open radical cystectomy and nephroureterectomy were included in the study. Simultaneous RARC and LNU significantly reduced bleeding volume and blood transfusion (P < .0001, P < .0001, respectively) and significantly prolonged operating time (P = .035). RARC and LNU significantly shortened hospitalization after operation (P = .003) and showed reduced tendency of postoperative complications within 30 days but not significantly (P = .25). Pathological characteristics and recurrence within 6 months were not significantly different between the two groups., Conclusion: Our results suggested that en bloc simultaneous RARC and LNU were safer surgical procedures with equivalent short-term oncological outcomes compared to conventional open procedures. It can be a standard minimally invasive surgical method in countries where robot-assisted radical nephroureterectomy is inaccessible., (© 2021 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Recent molecular characterization of primary urothelial carcinoma (UC) may guide future clinical decision-making. For metastatic UC (mUC), a comprehensive molecular characterization is still lacking. We analyzed whole-genome DNA and RNA sequencing data for fresh-frozen metastatic tumor biopsies from 116 mUC patients who were scheduled for palliative systemic treatment within the context of a clinical trial (NCT01855477 and NCT02925234). Hierarchical clustering for mutational signatures revealed two major genomic subtypes: GenS1 (67%), which was APOBEC-driven; and GenS2 (24%), which had a high fraction of de novo mutational signatures related to reactive oxygen species and is putatively clock-like. Significantly mutated genes (SMGs) did not differ between the genomic subtypes. Transcriptomic analysis revealed five mUC subtypes: luminal-a and luminal-b (40%), stroma-rich (24%), basal/squamous (23%), and a nonspecified subtype (12%). These subtypes differed regarding expression of key genes, SMGs, oncogenic pathway activity, and immune cell infiltration. We integrated the genomic and transcriptomic data to propose potential therapeutic options by transcriptomic subtype and for individual patients. This in-depth analysis of a large cohort of patients with mUC may serve as a reference for subtype-oriented and patient-specific research on the etiology of mUC and for novel drug development. PATIENT SUMMARY: We carried out an in-depth analysis of the molecular and genetic features of metastatic cancer involving the cells that line the urinary tract. We showed that this is a heterogeneous disease with different molecular subtypes and we identified possible targets for therapy for each subtype., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Although cisplatin-based chemotherapy is a standard treatment for urothelial carcinoma, it often causes acute kidney injury (AKI). AKI and dysfunction are observed in 25-35% of cisplatin-based chemotherapy patients, who may require treatment down-titration or withdrawal. In this study, we evaluated whether urinary L-FABP is a marker for early diagnosis of cisplatin-caused AKI., Methods: We included 42 adult patients who underwent cisplatin-based chemotherapy for bladder cancer or upper tract urothelial carcinoma from January 2018 to March 2019. Urinary L-FABP and serum creatinine were measured at 2 and 6 h, and 1, 2, 3, 7 and 28 days after taking cisplatin., Results: In the first week after receiving cisplatin, 10 patients (23.8%) were diagnosed with AKI (AKI + group). Pre-treatment (baseline) measurements did not significantly differ between the AKI + and AKI - groups. However, urinary L-FABP concentrations rapidly increased in the AKI + group and were significantly greater than in the AKI - group at Hour 2, Hour 6, Day 1 and Day 2. Serum creatinine also significantly differed between the AKI + group and the AKI - group on Days 3 and 7. ROC analysis was performed to evaluate the superiority of urinary L-FABP magnification which had the highest at the hour 6. The urinary L-FABP magnification and levels of aria under curve was 0.977. Based on ROC analysis, the best cut-off value of urinary L-FABP magnification was 10.28 times urinary L-FABP levels at the hour 0 (base line urinary L-FABP)., Conclusions: Acute renal function deterioration was predicted by increased urinary L-FABP excretion within 6 h after receiving CIS-CT and, in those with AKI, the increase in urinary L-FABP excretion preceded the rise in sCr by over 2 days. In contrast, no appreciable changes in urinary L-FABP levels were observed in patients with stable renal function throughout the whole observation period. So early increase in urinary L-FABP may identify patients at risk of cisplatin-induced AKI, who might benefit from treatment to prevent nephrotoxicity., Trial Registration: This study was retrospectively registered., (© 2022. The Author(s).)