Triple synchronous malignancies of the stomach, bladder and thyroid in a previously treated prostate cancer patient: A Case Report.

Cancers that develop within six months of the first primary cancer are referred to as synchronous malignancies. These malignancies are difficult to diagnose and treat, with treatment primarily based on case reports.

Endocrine immune-related adverse events in patients with metastatic renal and urothelial cancer treated with immune checkpoint-inhibitors.

PURPOSE: To evaluate the incidence, diagnosis and treatment of immune-related adverse events (e-irAE) of checkpoint inhibition (ICI) in metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC). METHODS: A retrospective, single-center study was conducted to identify a cohort that received ICI for mUC or mRCC. e-irAE were classified according to the CTCAE V.5.0. Patients received ICI for mUC or mCC between 01/2017 and 03/2021. A retrospective chart review was performed. T-Test, the chi-squared test, and Fisher's exact test were performed. RESULTS: 102 Patients received ICI [mUC: 40 (39%), mRCC: 62 (61%)]. 64 (63%) received an ICI monotherapy, 27 (27%) a dual ICI therapy, 11 (11%) a combination with VEGFi. e-irAE occurred in 19 (19%) patients [grade 1-2: 17 (84%), grade 3: 3 (16%)]. The median time until e-irAE was 42 days (range 11-211 days). 14 Patients developed thyroidism (14%), 4 (4%) a hypophysitis, 1 (1%) an adrenal insufficiency (AI). 7 patients (7%) had to discontinue ICI therapy [hypophysitis (100%), AI (100%), thyroidism (14%)]. 6 (86%) received cortisone. After a median range of 34 days 5 patients (71%) restarted ICI therapy. All patients (n = 4) with hypophysitis continued ICI [4 (100%) prednisone, 3 (75%) levothyroxine]. 11 (79%) presented with hyperthyroidism. 4 (37%) needed therapy (1 (7%) prednisone, 3 (21%) thiamazole, 2 (14%) beta blocker). The 9 (64%) patients with hypothyroidism received levothyroxine. Hypophysitis appears only on dual ICI (CTLA-4/PD-1) inhibition (p 0.007). CONCLUSION: This study shows the importance of adequate diagnosis and therapy of e-irAEs.

Cardiopulmonary effects of prolonged surgical abdominal retractors application during general anesthesia: a prospective observational comparative study

Abstract Introduction: Increasing abdominal pressures could affect pulmonary compliance and cardiac performance, a fact based on which the aim of the present study to detect the cardiopulmonary burden of multiple retractors application during supine versus lateral abdominal surgeries. We hypothesized that surgical ring multiple retractors application would affect the pulmonary and cardiac functions during both lateral and supine abdominal surgeries. Methods: Prospective observational comparative study on forty surgical patients subdivided into two groups twenty each, comparing pulmonary compliance and cardiac performance before, during and after retractors application, group (S) supine position cystectomy surgery, and group (L) lateral position nephrectomy surgery under general anesthesia, Composite 1ry outcome; dynamic compliance C-dyn and cardiac index CI and Other outcome variables ICON cardio-meter were also recorded. Results: C-dyn and C-stat were significantly decreased late during retractor application in lateral compared to supine surgery with significant decrease compared to basal values all over the surgical time. CI was significantly increased after retractor removal in both of the study groups compared to basal values. PAW P was significantly increased in -lateral compared to supine surgery -with significant increase compared to basal value all over the surgical time in both of the study groups. significant increase in DO2I compared to basal value during both supine and lateral positions. Conclusion: Surgical retraction results in a short-lived significant decreases in lung compliance and cardiac output particularly during the lateral-kidney position than the supine position compliance.

Intravesical oncolytic virotherapy and immunotherapy for non-muscle-invasive bladder cancer mouse model.

OBJECTIVES: To test if intravesical instillation of both an anti-programmed cell death protein 1 (PD-1) inhibitor and an oncolytic reovirus would demonstrate a greater effect than either treatment alone, as non-muscle-invasive bladder cancer that is refractory to intravesical bacillus Calmette-Guérin can be treated by systemic anti-PD-1 immunotherapy and we previously demonstrated improved overall survival (OS) with six once-weekly instillations of intravesical anti-PD-1 in a murine model. MATERIALS AND METHODS: Using an orthotopic syngeneic C3H murine model of MBT2 urothelial bladder cancer, groups of 10 mice were compared between no treatment, intravesical anti-PD-1, intravesical oncolytic reovirus, or intravesical reovirus + anti-PD-1. A single intravesical treatment session was given. The primary outcome was OS, and the secondary outcomes included long-term immunity and tumour-immune profile. RESULTS: With a median follow-up of 9 months, all mice that received no treatment died with a median survival of 41 days, while the comparison median OS was not reached for reovirus (hazard ratio [HR] 14.4, 95% confidence interval [CI] 3.9-32.6; P < 0.001), anti-PD-1 (HR 28.4, 95% CI 7.0-115.9; P < 0.001), and reovirus + anti-PD-1 (HR 28.4, 95% CI 7.0-115.9; P < 0.001). Monotherapy with anti-PD-1 or reovirus demonstrated no significant differences in survival (P = 0.067). Mass cytometry showed that reovirus + anti-PD-1 treatment enriched monocytes and decreased myeloid-derived suppressor cells, generating an immuno-responsive tumour microenvironment. Depletion of CD8+ T cells eliminated the survival advantage provided by the intravesical treatment. CONCLUSIONS: Treatment of murine orthotopic bladder tumours with a single instillation of intravesical reovirus, anti-PD-1 antibody, or the combination confers superior survival compared to controls. Tumour-immune microenvironment differences indicated myeloid-derived suppressor cells and CD8+ T cells mediate the treatment response.

Cardiopulmonary effects of prolonged surgical abdominal retractors application during general anesthesia: a prospective observational comparative study.

INTRODUCTION: Increasing abdominal pressures could affect pulmonary compliance and cardiac performance, a fact based on which the aim of the present study to detect the cardiopulmonary burden of multiple retractors application during supine versus lateral abdominal surgeries. We hypothesized that surgical ring multiple retractors application would affect the pulmonary and cardiac functions during both lateral and supine abdominal surgeries. METHODS: Prospective observational comparative study on forty surgical patients subdivided into two groups twenty each, comparing pulmonary compliance and cardiac performance before, during and after retractors application, group (S) supine position cystectomy surgery, and group (L) lateral position nephrectomy surgery under general anesthesia, Composite 1ry outcome; dynamic compliance C-dyn and cardiac index CI and Other outcome variables ICON cardio-meter were also recorded. RESULTS: C-dyn and C-stat were significantly decreased late during retractor application in lateral compared to supine surgery with significant decrease compared to basal values all over the surgical time. CI was significantly increased after retractor removal in both of the study groups compared to basal values. PAWP was significantly increased in -lateral compared to supine surgery -with significant increase compared to basal value all over the surgical time in both of the study groups. significant increase in DO2I compared to basal value during both supine and lateral positions. CONCLUSION: Surgical retraction results in a short-lived significant decreases in lung compliance and cardiac output particularly during the lateral-kidney position than the supine position compliance.

The impact of preoperative immune checkpoint inhibitors on kidney and bladder cancer surgeries: a systematic review☆.

Therapies based on the use of immune checkpoint inhibitors (ICIs), such as nivolumab, pembrolizumab, ipilimumab, atezolizumab, avelumab, and durvalumab, have proven effective in the treatment of metastatic urological neoplasms. Recently, it has been hypothesized that the use of this type of treatment prior to surgery could lead to an increased difficulty in renal and bladder surgeries. The literature concerning this topic, however, is still scarce and non-consensual. In our systematic review, we used the PRISMA guidelines methodology to search the pertinent literature available up to June 18, 2020 in PubMed. Additionally, we searched the related grey literature in the abstracts of the meetings of the American Society of Clinical Oncology (ASCO), American Society of Clinical Oncology Genitourinary (ASCO-GU), European Society of Medical Oncology (ESMO), and American Urological Association (AUA) from 2015 to 2020. We were able to find only 16 publications that addressed the use of ICIs prior to surgery in kidney and bladder neoplasms. The results were conflicting, and usually the issue of surgical difficulties after the use of ICIs was not directly approached. We hope that our publication may raise the awareness towards the need to further investigate the effects of neoadjuvant ICIs on surgical outcomes in urologic cancers.

Outcome of orthotopic sigmoid versus ileal neobladder reconstruction.

INTRODUCTION: Radical cystectomy with orthotopic urinary diversion is considered the gold standard for treatment of muscular invasive bladder cancer or high-risk nonmuscular invasive bladder cancer. The choice of orthotopic neobladder reconstruction depends on the clinical outcomes of it and should be planned with the patients, especially the risk of incontinence. METHODS: this study included 52 Egyptian patients underwent radical cystectomy and orthotopic neobladder reconstruction with sigmoid (25 patients) and ileal (27 patients) segments. Postoperative clinical outcomes between the sigmoid and ileal neobladder groups were compared. RESULTS: In the present study, 12 intraoperative complications (6 in each group) and 19 postoperative complications (17 in sigmoid and 15 in ileal group) occurred; however, there was no significant difference in the incidence of intraoperative and postoperative complications between both groups. There were no significant differences in the continence status and spontaneous voiding between both groups. There were no significant differences in maximal flow rate and voided volume between both groups. Night voiding frequency in the ileal neobladder patients was significantly smaller than sigmoid neobladder patients. Free flowery showed a significant difference of voiding time and volume in favor of sigmoid neobladder group. Maximum urethral pressure and urethral closing pressure were significantly higher in ileal neobladder group. CONCLUSIONS: Both types of neobladder reconstruction resulted in comparatively satisfactory outcomes; however, the voiding function in sigmoid neobladder group appeared to be more favorable than that in ileal neobladder group.

Is there a role for second transurethral resection in pTa high-grade urothelial bladder cancer?

INTRODUCTION: Evidence for second transurethral resection of bladder tumour (TURBT) for pTa high-grade lesions is limited. This study aims to examine the role of a second TURBT in the pTa high-grade group and to generate recurrence and progression data for this group. MATERIAL AND METHODS: We retrospectively studied the clinical profiles and outcomes of all patients diagnosed with high-grade pTa lesions at first TURBT, between the years 2006-2015. Firstly, in patients who underwent a complete first TURBT, we calculated the proportion of patients with positive findings on second TURBT. Secondly, we assessed whether those who underwent a second TURBT had a longer recurrence-free survival compared to those who underwent a single TURBT. RESULTS: One hundred and twelve patients had a pTa high-grade urothelial bladder tumor (WHO 2004 classification) at first TURBT, out of whom 43 (38.3%) had a second TURBT. Indications for second TURBT were high-grade lesions (n = 36), absence of detrusor muscle (n = 2), and incomplete resection (n = 5). Out of the 36 patients who had a complete first TURBT and underwent a second look TURBT, 7 patients had positive findings (3 carcinoma in situ, 2 pTa low-grade lesions and 2 pTa high-grade lesions) and there was no upstaging. Of the 5 patients with an incomplete first TURBT, one upstaged to pT1 on second TURBT. Of the 81 patients who followed up with us, 25.9% had a recurrence and 8.6% progressed. The estimated median recurrence free survival was 60 months (95% CI 29.2-90.7) for the whole group and 76 months vs. 45 months for the second and single TURBT group respectively - a difference that was clinically, though not statistically, significant. Multiple (≥2) tumours had a lower recurrence free survival (HR of 4.60, CI 1.67-12.63, p = 0.003). CONCLUSIONS: Of the patients with pTa high-grade tumours who had a second TURBT after a complete first TURBT, 19.4% had a positive finding. Multiple tumours are four times as likely to recur as solitary tumours. The role of a second TURBT in this group needs to be studied in larger patient cohorts before a recommendation regarding its lack of clinical utility can be made conclusively.

ß-catenin and SKP2 proteins as predictors of grade and stage of non-muscle invasive urothelial bladder carcinoma.

BACKGROUND: To evaluate the expression of beta-catenin (ß-catenin) and SKP2 proteins in superficial bladder cancer cases and their correlation with tumor grade and stage. METHODS: After institutional review board approval, we retrospectively evaluated the expression of ß-catenin and SKP2 proteins in tissue specimens from patients with non-muscle invasive bladder cancer (NMIBC) and compared their results with a cohort of chronic nonspecific cystitis's. Then we and explored these markers association with tumor grade and stage. RESULTS: A total of 40 patients were retrospectively identified, 50% was NMIBC and the rest were chronic nonspecific cystitis. ß-catenin was expressed in 18 (90%) patients of the NMIBC group in comparison to 14 (70%) of the control group with (P=0.1), while SKP2 protein was only expressed in NMIBC groups (P=0.03). A statistically significant correlation was identified between nucleocytoplasmic localization of ß-catenin and SKP2 with tumor grade, stage. CONCLUSIONS: ß-catenin and SKP2 expression are providing promising results for differentiating higher grade and stage non muscle invasive bladder cancers.

Orthotopic genital sparing radical cystectomy in pre-menopausal women with muscle-invasive bladder carcinoma: A prospective study.

INTRODUCTION: Invasive cancer bladder is a life-threatening disease that is best treated with radical cystectomy and a suitable urinary diversion. The aim of this study was to evaluate the oncological outcome, voiding and sexual functions after genital sparing radical cystectomy with orthotopic bladder reconstruction in pre-menopausal women with bladder cancer. MATERIALS AND METHODS: 18 pre-menopausal women who underwent radical cystectomy and orthotopic urinary diversion with preservation of genital organs were included for this study. The patients were followed-up clinically and radiologically to assess their oncological outcome in addition to their voiding and sexual function. RESULTS: Mean age of the patients was 37.8 years, and the median follow-up after surgery was 70 months. One patient was lost to follow-up at 12 months post-operatively. The surgery was completed as planned in all patients, with a mean operative time of 290 min and an average blood loss of 750 mL. 14 patients were able to void satisfactorily, being continent day and night, while four patients needed clean intermittent catheterization. Sexual life remained unchanged in 15 cases, while three patients reported dysparunea. Till the last follow-up, there was no local recurrence while distant metastases were detected in three cases, two of whom died. CONCLUSIONS: Genital sparing cystectomy is a valid option for managing carefully selected women with muscle-invasive bladder cancer with good functional and sexual outcomes.

Primary urachal mucinous adenocarcinoma of the urinary bladder.

Urinary bladder cancer is the second most frequent tumour of the genitourinary tract with bladder adenocarcinoma comprising for about 0.5-2% of all malignant bladder tumours. Other primary sites for such tumours include rectum, stomach, endometrium, breast, prostate, seminal vesicles and ovaries. Such non-urothelial bladder tumours with intramural bladder tumour growth may delay the onset of symptoms which may lead to a delay in the diagnosis and thereby adversely affecting the prognosis as compared to urothelial bladder tumours. Traditionally bladder adenocarcinomas were believed to be resistant to both chemotherapy and radiotherapy, but recent advancements have shown encouraging responses with adjuvant chemotherapy and radiotherapy. We present here a case of primary urachal mucinous adenocarcinoma of the urinary bladder highlighting their relative rarity of occurrence and the difficulties encountered in diagnosing primary bladder mucinous adenocarcinoma.