An unusual "linitis plastica" like breast cancer bladder metastasis.

Breast cancer (BrC) is the most frequently diagnosed malignancy in woman and most BrC related deaths are due to metastasis. BrC frequently metastasizes to the lymph nodes, liver, lung, bone and brain while the urinary bladder is considered as an unusual site for breast metastasis. We report a case of bladder metastasis identified in a patient with past BrC history, presenting with hematuria, low urinary tract symptoms, and hydronephrosis.

Mucinous appendiceal adenocarcinoma invading the bladder: not always an easy diagnosis. A case report.

Appendiceal neoplasms account for less than 1% of intestinal cancers and their clinical manifestation is typically, nonspecific and ambiguous. Appendiceal tumor infiltrating the urinary tract is extremely rare and few cases are mentioned in literature. A 72-year-old woman presented gross hematuria and right colic pain. No prior urologic disease was reported. Cystoscopic examination showed a large lesion on the right side of posterior bladder wall, with multiple ulcerated areas and microscopical examination of the specimen revealed a mucinous adenocarcinoma infiltrating urinary bladder. Contrast-enhanced computed tomography (CT) scan identified focal thickening of bladder dome 21 × 7 cm with a possible origin from the appendix and with an unclear relationship with the uterus and the right fallopian tube. These findings were discussed with the local gastrointestinal multidisciplinary team, where a decision to perform upfront surgery was made. Explorative laparotomy confirmed a tumor of the appendix invading the urinary bladder. We performed an en-bloc resection including right colon, 40 cm of terminal ileum with a partial cystectomy removing the infiltrated area of the right bladder wall, and an omentectomy. Reconstruction was made first with a full-thickness suture of the bladder, then with an ileo-colon stapled anastomosis. The postoperative course was uneventful and the CT scan at 9 months from surgery did not show any recurrence. Right hemicolectomy is considered the gold standard for all lesions with invasion beyond the mucosa, and, appendicectomy alone seems to be the ideal treatment for in situ and localized cases.

Increased risk of secondary bladder cancer after radiation therapy for endometrial cancer.

To investigate the effect of radiation therapy (RT) after endometrial cancer (EC) diagnosis on the risk of occurring secondary bladder cancer (SBC) as well as on the survival outcome of those patients who suffered with SBC. Data was extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2015. Chi-squared test was utilized to compare clinicopathological characteristics among different groups. The Fine and Gray's competing risk model was utilized to assess cumulative incidence and risk of occurring SBC in EC survivors. The Kaplan-Meier method and the Cox regression model were used for survival analysis. As a result, a total of 108,060 EC patients were included, among which 37,118 (34.3%) patients received RT while others did not. The incidence of SBC was 1.31%, 1.76% and 0.96% among patients who received prior brachytherapy, external-beam radiotherapy (EBRT) and others, respectively. Both of the EBRT (standardized incidence ratio (SIR) = 2.24, 95% CI [1.94-2.58]) and brachytherapy (SIR = 1.76, 95% CI [1.44-2.13]) group had a higher incidence of SBC than the general population in USA. The competing risk analysis demonstrated that receiving EBRT (HR = 1.97, 95% CI [1.64-2.36]) or brachytherapy (HR = 1.46, 95% CI [1.14-1.87]) were all independent risk factors for developing SBC. A survival detriment was only observed in SBC patients who received prior EBRT after EC diagnosis, but not for brachytherapy, when compared with those who did not undergo RT. Additionally, there were no significant survival differences between primary bladder cancer and SBC with or without prior RT history. Patients who underwent RT after EC had an increased risk of developing bladder cancer as secondary primary cancer. The prognosis of these SBC patients varied depending on types of RT that received after EC diagnosis.

The feasibility of reduced field-of-view diffusion-weighted imaging in evaluating bladder invasion of uterine cervical cancer.

OBJECTIVES: Uterine cervical cancer with bladder mucosal invasion is classified as FIGO stage IVA with poor prognosis. MRI can rule out the bladder invasion and skipping cystoscopy may be possible; however, high false-positive rate may be problematic. The purpose of this study is to evaluate the diagnostic performance of reduced field-of-view (FOV) diffusion-weighted imaging (DWI) in evaluating bladder mucosal invasion of cervical cancer. METHODS: 3T MRI including T2WI and reduced FOV DWI in 15 women with histologically proven cervical cancer (two stage IIIB, six stage IVA, seven stage IVB) were retrospectively evaluated compared with cystoscopic findings. RESULTS: Cystoscopy revealed mucosal invasion in 13 of 15 cases. The border between the tumor and the bladder wall was unclear on T2WI and clear on reduced FOV DWI in all 15 cases. The diagnosis of mucosal invasion on reduced FOV DWI had a sensitivity of 100%, specificity of 50%, accuracy of 93%, PPV of 93%, and NPV of 100%. CONCLUSIONS: Addition of reduced FOV DWI may improve the staging accuracy of MRI for cervical cancer in assessing the bladder mucosal invasion. ADVANCES IN KNOWLEDGE: Reduced FOV DWI may improve the staging accuracy of cervical cancer in assessing bladder mucosal invasion with high NPV and PPV, which may be helpful for avoiding unnecessary cystoscopy.

Knockdown of CXCL5 inhibits the invasion, metastasis and stemness of bladder cancer lung metastatic cells by downregulating CD44.

In our previous studies, we found that T24 lung metastatic cancer cells showed high invasion and metastasis abilities and cancer stem cell characteristics compared with T24 primary cancer cells. By screening for the expression of CXC chemokines in both cell lines, we found that CXCL5 is highly expressed in T24-L cells. The aim of this study is to shed light on the relationship of CXCL5 with epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). RNAi technology was used to decrease CXCL5 expression in the T24-L cell line, and the EMT and CSCs of the shCXCL5 group and the control group were compared. The CXCR2 inhibitor SB225002 was used to inhibit the receptor of CXCL5 to determine the effect of the CXCL5/CXCR2 axis. The knockdown of CXCL5 expression in T24-L cells reduced their EMT and CSC characteristics. RT-PCR and Western blot analyses revealed the downregulation of N-cadherin, Vimentin and CD44. In addition, when CD44 expression was knocked down, the EMT ability of the cells was also inhibited. This phenomenon was most pronounced when both CXCL5 and CD44 were knocked down. CXCL5 and CD44 can affect the EMT and stem cell capacity of T24-L cells through some interaction.

An unusual presentation of synchronous bladder metastases from an oesophageal adenocarcinoma.

Adenocarcinoma of the bladder is a rare form of malignancy accounting for fewer than 2% of bladder tumours. It is most commonly a result of direct invasion from prostatic, rectal or gynaecological primaries and less commonly presents from distant haematological or lymphatic metastasis. We report a rare case of oesophageal carcinoma metastasising to the bladder. It involves a 71-year-old man with progressive dysphagia and diagnostic computerised tomography findings of thickening in the oesophagus, bladder and common bile duct. Subsequent endoscopic biopsies of the oesophageal and bladder abnormalities showed immunohistochemical features consistent with upper gastrointestinal malignancy. This report aims to add to current clinical evidence of this route of metastasis and also highlight some of the key markers used by pathologists in interpretation of specimens. It also emphasises the essential role of a multidisciplinary approach for the diagnosis of such rare conditions.

Risk Factors for Intravesical Recurrence after Minimally Invasive Nephroureterectomy for Upper Tract Urothelial Cancer (ROBUUST Collaboration).

PURPOSE: Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) has an incidence of approximately 20%-50%. Studies to date have been composed of mixed treatment cohorts-open, laparoscopic and robotic. The objective of this study is to assess clinicopathological risk factors for intravesical recurrence after RNU for UTUC in a completely minimally invasive cohort. MATERIALS AND METHODS: We performed a multicenter, retrospective analysis of 485 patients with UTUC without prior or concurrent bladder cancer who underwent robotic or laparoscopic RNU. Patients were selected from an international cohort of 17 institutions across the United States, Europe and Asia. Univariate and multiple Cox regression models were used to identify risk factors for bladder recurrence. RESULTS: A total of 485 (396 robotic, 89 laparoscopic) patients were included in analysis. Overall, 110 (22.7%) of patients developed IVR. The average time to recurrence was 15.2 months (SD 15.5 months). Hypertension was a significant risk factor on multiple regression (HR 1.99, CI 1.06; 3.71, p=0.030). Diagnostic ureteroscopic biopsy incurred a 50% higher chance of developing IVR (HR 1.49, CI 1.00; 2.20, p=0.048). Treatment specific risk factors included positive surgical margins (HR 3.36, CI 1.36; 8.33, p=0.009) and transurethral resection for bladder cuff management (HR 2.73, CI 1.10; 6.76, p=0.031). CONCLUSIONS: IVR after minimally invasive RNU for UTUC is a relatively common event. Risk factors include a ureteroscopic biopsy, transurethral resection of the bladder cuff, and positive surgical margins. When possible, avoidance of transurethral resection of the bladder cuff and alternative strategies for obtaining biopsy tissue sample should be considered.

The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis.

PURPOSE: Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities. MATERIALS AND METHODS: Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis. RESULTS: In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01). CONCLUSIONS: Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences.

Avelumab first-line maintenance in locally advanced or metastatic urothelial carcinoma: Applying clinical trial findings to clinical practice.

Although urothelial carcinoma (UC) is considered a chemotherapy-sensitive tumor, progression-free survival and overall survival (OS) are typically short following standard first-line (1L) platinum-containing chemotherapy in patients with locally advanced or metastatic disease. Immune checkpoint inhibitors (ICIs) have antitumor activity in UC and favorable safety profiles compared with chemotherapy; however, trials of 1L ICI monotherapy or chemotherapy + ICI combinations have not yet shown improved OS vs chemotherapy alone. In addition to direct cytotoxicity, chemotherapy has potential immunogenic effects, providing a rationale for assessing ICIs as switch-maintenance therapy. In the JAVELIN Bladder 100 phase 3 trial, avelumab administered as 1L maintenance with best supportive care (BSC) significantly prolonged OS vs BSC alone in patients with locally advanced or metastatic UC that had not progressed with 1L platinum-containing chemotherapy (median OS, 21.4 vs 14.3 months; hazard ratio, 0.69 [95% CI, 0.56-0.86]; P = 0.001). Efficacy benefits were seen across various subgroups, including recipients of 1L cisplatin- or carboplatin-based chemotherapy, patients with PD-L1+ or PD-L1- tumors, and patients with diverse characteristics. Results from JAVELIN Bladder 100 led to the approval of avelumab as 1L maintenance therapy for patients with locally advanced or metastatic UC that has not progressed with platinum-containing chemotherapy. Avelumab 1L maintenance is also included as a standard of care in treatment guidelines for advanced UC with level 1 evidence. This review summarizes the data that supported these developments and discusses practical considerations for administering avelumab maintenance in clinical practice, including patient selection and treatment management.

Bladder-to-bladder metastasis: gallbladder cancer metastasising to the urinary bladder.

We report a 48-year-old fit and healthy woman who was incidentally diagnosed to have adenocarcinoma of gallbladder after laparoscopic cholecystectomy. Subsequent imaging showed no evidence of regional or distant spread. She was scheduled for elective laparotomy and resection of gallbladder bed, but during laparotomy frozen section analysis of an incidentally discovered peritoneal deposit confirmed metastasis, so the procedure was abandoned. Thereafter, she received cisplatin and gemcitabine chemotherapy. However, surveillance computed tomography incidentally noted a urinary bladder mass which had not been present before. Transurethral resection of the bladder lesion revealed moderately differentiated adenocarcinoma of urinary bladder. The appearance and immunoprofile of the lesion confirmed metastasis from the primary gallbladder cancer, which has not been documented in the literature to the best of our knowledge. Her disease progressed and she is being challenged with gemcitabine and carboplatin as second-line palliative chemotherapy. She is still alive two years after the initial diagnosis.

Difficult differential diagnosis of bladder pedicled masses about metastasis from non-small cell lung cancer: A case report.

Differential diagnoses of primary bladder tumors from metastasis ones can be difficult, for the symptom and imaging findings are pretty similar. Here, we reported a case of bladder metastasis from lung adenocarcinoma. A 73-year-old female patient who was diagnosed with bladder metastasis from lung adenocarcinoma presented as gross hematuria and multiple pedicled masses in the bladder on MRI scan. Such clinical manifestations were easily misdiagnosed as primary bladder malignancy. Additionally, the tumor samples of this case were further harvested and processed for histopathological analysis and gene detections to confirm this case as a metastasis tumor that was refractory to the subsequent therapy. Diagnosis of bladder metastasis should be paid more consideration in patients with a history of cancer despite the fact that primary bladder malignancy accounts for the majority of bladder masses.

A Case of Ewing Sarcoma of the Bladder Presenting in Early Infancy.

A 6-week-old female presented with gross hematuria and was diagnosed with Ewing sarcoma of the bladder through ultrasound and cystoscopic biopsies, along with a negative metastatic workup. She was treated with transurethral resection, chemotherapy consisting of with vincristine, cycolphosphamide, doxorubicin, ifosfamide and etoposide, and partial cystectomy. After completing chemotherapy, the patient has been doing well with no evidence of disease. There have been 14 other cases, 4 pediatric, of Ewing sarcoma of the bladder reported. To our knowledge, our case is the youngest patient reported with this disease.

Optimal Time Point for 68Ga-PSMA-11 PET/CT Imaging in the Assessment of Suspected Metastatic Prostate Cancer in the Bladder of Postprostatectomy Patient.

ABSTRACT: A 77-year-old man with prostate cancer had prostatectomy and hormonal therapy and underwent pelvic MRI and 68Ga-PSMA-11 PET/CT during clinical follow-up. A pelvic MRI scan showed suspected metastasis along the posterior wall of urinary bladder. The 68Ga-PSMA-11 PET/CT was acquired in a dual-time point fashion, at 60 minutes and 110 minutes postinjection. At 60 minutes postinjection, the known bladder wall lesion showed lower than urine background uptake. On 110 minutes delayed images, the bladder wall lesion showed avid PSMA uptake, much higher than the urine background, increased PSMA uptake by the tumor over time, and improved contrast in the lesion.

Effects of Complete Bladder Cuff Removal on Oncological Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

PURPOSE: This study aimed to evaluate the effects of bladder cuff method on oncological outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. MATERIALS AND METHODS: The records of 1,095 patients treated with RNU performed at our hospital between 1994 and 2018 were retrospectively reviewed; 856 patients with no bladder tumor history were enrolled in the present study. The management of bladder cuff was divided into two categories: extravesical ligation (EL) or transvesical resection (TR). Survival was analyzed using the Kaplan-Meier method and Cox regression analyses were performed to determine which factors were associated with intravesical recurrence (IVR)-free survival (IVRFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The mean patient age was 64.8 years and the median follow-up was 37.7 months. Among the 865 patients, 477 (55.7%) underwent the TR and 379 (44.3%) the EL. Significantly higher IVRFS (p=0.001) and OS (p=0.013) were observed in the TR group. In multivariable analysis, IVR, CSS, and OS were independently associated with the EL. Among 379 patients treated with the EL, eight underwent remnant ureterectomy. Based on radical cystectomy-free survival, significant difference was not observed between the two groups. However, significantly higher IVRFS was observed in the TR group when the tumor was located in the renal pelvis. CONCLUSION: Intramural complete excision of the distal ureter during RNU should be the gold standard approach compared with EL for the management of distal ureter in terms of oncological outcomes.

The diagnostic and clinicopathological value of trefoil factor 3 in patients with gastric cancer: a systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic value of Trefoil factor 3 (TFF3) and the correlation between TFF3 expression and clinicopathological features in patients with gastric cancer (GC). METHODS: PubMed, The Cochrane, EMbase, and Web of Science were retrieved comprehensively to collect relevant literature. The search ended on 31 May 2020. All data were analyzed using PubMed, The Cochrane, EMbase, and Web of Science were retrieved to collect relevant articles. All data from the included studies were subjected to meta-analysis using Stata 12.0 software. RESULTS: Seventeen studies involved 4654 subjects were included. For the diagnostic value of TFF3 for GC, the sensitivity, specificity, and AUC were 0.71, 0.80, and 0.80, respectively. For the clinicopathological value of TFF3, tissue TFF3 expression showed a higher risk of lymph node metastasis (OR 2.20, 95% CI 1.75-2.78, p < 0.001) and muscularis propria invasion (≥T2) (1.51, 1.13-2.03, p = 0.006), as well as worse TNM stage (2.26, 1.63-3.12, p < 0.001) and histological type (1.72, 1.34-2.20, p < 0.001), while no apparent relationship was found for serous membrane invasion (T4), venous invasion, and peritoneal metastasis. CONCLUSION: TFF3 may be a promising biomarker for GC, and the TFF3 expression is likely to be involved in the invasion, metastasis, and differentiation of GC.

Robotic Low Anterior Resection and Partial Bladder Resection for Management of Locoregional Endometrial Cancer Recurrence.

OBJECTIVE: To demonstrate a robotic tumor debulking for management of locoregional endometrial cancer recurrence. DESIGN: Case report. SETTING: Tertiary referral center in New Haven, CT. INTERVENTIONS: A 70-year-old patient with a history of stage IB endometrioid endometrial cancer presented with rectal bleeding 3 years after the completion of treatment. A mass involving the distal sigmoid colon/upper rectum and bilateral distal periureteral masses were visualized on imaging. There was no distant metastatic disease. Colonoscopic biopsies were consistent with endometrial cancer recurrence. Because the patient was symptomatic with rectal bleeding and had no distant metastasis, it was recommended that she undergo surgical resection for management of this locoregional recurrence. The patient was placed in reverse Trendelenburg position with a rightward tilt to mobilize the splenic flexure. Once the cephalad aspect of the descending colon mobilization was completed, the patient was placed in Trendelenburg lithotomy position to expose the pelvis. A robot was docked at this point and the pelvic avascular spaces were delineated. A medial-to-lateral approach was used in mobilization of the sigmoid colon mesentery. The left ureter was identified and the sigmoid branches of inferior mesenteric artery were sealed. The descending/sigmoid colon junction was stapled. After complete mobilization of the sigmoid colon, the tumor-free upper rectum was delineated and stapled. Attention was then turned to the distal peri-ureteral masses. The 2-cm mass on the right, which was densely adherent to the distal right ureter, was completely resected after extensive ureterolysis. The resection of the 4-cm mass on the left which involved both the distal left ureter and the bladder dome required an intentional cystotomy and a partial cystectomy to attain negative margins (Supplemental Figure 1). The procedure was continued with the bowel anastomosis. The anvil was introduced through the vagina and was placed into the proximal limb through an antimesenteric incision. An end-to-end tension-free anastomosis was performed and adequate vascularization was confirmed with intravenous indocyanine green. CONCLUSION: Robotic low anterior resection and partial bladder resection were performed without any complications with negative margins. Robotic tumor debulking should be considered in appropriate patients when managing locoregional recurrence of endometrial cancer [1,2].

The clinicopathological characteristics of muscle-invasive bladder recurrence in upper tract urothelial carcinoma.

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.

From clinical trials to clinical use of checkpoint inhibitors for patients with metastatic urothelial cancer.

Monoclonal antibodies targeting the checkpoint inhibitors (CPIs), programmed cell death protein-1 or programmed cell death ligand-1, are changing the landscape of urothelial carcinoma therapeutics. Overall, clinical studies in metastatic or advanced urothelial cancer showed that CPIs provided a slight improvement in survival and a relevant advantage in safety, compared with chemotherapy. After reviewing published and ongoing trials, the authors discuss expected answers to unmet needs, with a special attention to the research of biological markers for patients with urothelial cancer eligible for treatment with CPIs in this article.