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European Urology May 2024Circulating tumor DNA (ctDNA) can be used for sensitive detection of minimal residual disease (MRD). However, the probability of detecting ctDNA in settings of low tumor...
BACKGROUND AND OBJECTIVE
Circulating tumor DNA (ctDNA) can be used for sensitive detection of minimal residual disease (MRD). However, the probability of detecting ctDNA in settings of low tumor burden is limited by the number of mutations analyzed and the plasma volume available. We used a whole-genome sequencing (WGS) approach for ctDNA detection in patients with urothelial carcinoma.
METHODS
We used a tumor-informed WGS approach for ctDNA-based detection of MRD and evaluation of treatment responses. We analyzed 916 longitudinally collected plasma samples from 112 patients with localized muscle-invasive bladder cancer who received neoadjuvant chemotherapy (NAC) before radical cystectomy. Recurrence-free survival (primary endpoint), overall survival, and ctDNA dynamics during NAC were assessed.
KEY FINDINGS AND LIMITATIONS
We found that WGS-based ctDNA detection is prognostic for patient outcomes with a median lead time of 131 d over radiographic imaging. WGS-based ctDNA assessment after radical cystectomy identified recurrence with sensitivity of 91% and specificity of 92%. In addition, genomic characterization of post-treatment plasma samples with a high ctDNA level revealed acquisition of platinum therapy-associated mutational signatures and copy number variations not present in the primary tumors. The sequencing depth is a limitation for studying tumor evolution.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Our results support the use of WGS for ultrasensitive ctDNA detection and highlight the possibility of plasma-based tracking of tumor evolution. WGS-based ctDNA detection represents a promising option for clinical use owing to the low volume of plasma needed and the ease of performing WGS, eliminating the need for personalized assay design.
PATIENT SUMMARY
Detection of tumor DNA in blood samples from patients with cancer of the urinary tract is associated with poorer outcomes. Disease recurrence after surgery can be identified by the presence of tumor DNA in blood before it can be detected on radiography scans.
PubMed: 38811314
DOI: 10.1016/j.eururo.2024.05.014 -
International Journal of Surgery Case... Jul 2024Primary urachal adenocarcinoma (PUA) is a rare form of cancer that arises from the urachus, a vestigial remnant of the allantois and cloaca during embryonic development....
INTRODUCTION AND IMPORTANCE
Primary urachal adenocarcinoma (PUA) is a rare form of cancer that arises from the urachus, a vestigial remnant of the allantois and cloaca during embryonic development. The exact pathogenesis of PUA is not well understood, but it is believed to arise from glandular epithelium remnants within the urachus. The rarity of this type of cancer makes it difficult to comprehensively study its epidemiology.
CASE PRESENTATION
This case report describes a 47-year-old male patient who presented with intermittent painless hematuria and fatigue for two months. Cystoscopy showed a single growth at the dome of the urinary bladder, and abdominopelvic CT scan with contrast revealed a 3*2 cm enhancing growth at the dome of the bladder suspicious of urachal origin tumor. The patient was diagnosed with urachal adenocarcinoma (PT2) after pathological examination. The patient underwent partial cystectomy and umbilicectomy.
CLINICAL DISCUSSION
Patients with PUA often present with nonspecific symptoms that can delay the diagnosis. The most common symptom is hematuria, which is present in approximately two-thirds of the patients. The diagnosis of PUA is challenging and relies on a combination of clinical presentation, imaging, and histopathological examination.
CONCLUSION
The mainstay of treatment for PUA is surgical resection, which may include partial cystectomy or radical cystectomy with en bloc resection of the urachus and umbilicus. It is esential to report all cases of primary urachal adenocrcinoma.
PubMed: 38810293
DOI: 10.1016/j.ijscr.2024.109791 -
Frontiers in Oncology 2024There is a sparsity of literature on treatment outcomes for patients with non-muscle invasive bladder cancer (NMIBC) who received neoadjuvant chemotherapy (NAC). We aim...
BACKGROUND
There is a sparsity of literature on treatment outcomes for patients with non-muscle invasive bladder cancer (NMIBC) who received neoadjuvant chemotherapy (NAC). We aim to analyze the outcomes associated with the use of NAC prior to radical cystectomy for NMIBC utilizing the National Cancer Database.
MATERIALS/METHODS
The National Cancer Database bladder dataset was evaluated for patients with NMIBC and known pT staging undergoing RC from 2006-2016. The primary outcome was the utilization of NAC. The secondary outcomes were pathologic down staging to pT0, positive surgical margins, 30-day readmission, and overall survival.
RESULTS
The proportion of patients receiving NAC prior to radical cystectomy for NMIBC increased from 8.6% in 2006 to 14.8% in 2016. Those who received NAC had significantly higher tumor stages (cT1 vs cTa/is) with 85.7% of patients receiving NAC presenting with cT1 as opposed to only 82% in those not receiving NAC (p < 0.001). Similarly, there were significantly more patients who were cN+ in the NAC group as compared to those who did not receive NAC (5.5% vs. 1.1%, p < 0.001). For patients who received NAC, the rate of downstaging to pT0 was 12.7% as compared to only 3.3% in patients who did not receive NAC (p < 0.001). There was no significant difference comparing the rates of positive margins or 30-day readmissions between groups. On multivariable logistic regression for pathologic downstaging, NAC was significant (OR 4.1, p < 0.05). There was no significant difference in overall survival between patients treated with or without NAC.
CONCLUSION
NAC prior to RC in patients with NMIBC has increased in recent years and correlates with tumor downstaging. Further research is requisite to identify patients who obtain the greatest benefit of NAC in the NMIBC setting.
PubMed: 38807772
DOI: 10.3389/fonc.2024.1392062 -
Heliyon May 20246-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to...
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to evaluate the prognostic significance of PFKFB3 in bladder cancer (BLCA) patients by analyzing a combination of publicly available databases, clinical patient data, and bladder tumor samples from our hospital. Single-cell and bulk RNA-seq data of bladder cancer, obtained from ENA, GEO, and TCGA databases, were utilized for our analysis. The results indicated that PFKFB3 mRNA expression was markedly elevated in bladder cancer compared to paired normal tissue. Furthermore, BLCA patients with high PFKFB3 expression exhibited a significantly worse prognosis (P < 0.05). To validate these findings, clinical data and immunohistochemistry staining were performed on specimens obtained from 89 BLCA patients who underwent radical cystectomy at either Qingdao University Affiliated Hospital or Peking Union Medical College Hospital. The findings from this verification process confirmed that high expression of PFKFB3 serves as a biomarker for predicting worse prognosis in BLCA patients (OR: 2.462, 95 % CI: 1.202-5.042, P = 0.012). To facilitate clinical application, we developed a nomogram based on four variables, including PFKFB3 expression, to predict the survival of BLCA patients. Importantly, this nomogram demonstrated a low mean prediction error of 0.03. Taken together, our findings suggest that PFKFB3 has the potential to serve as both a prognostic biomarker and a therapeutic target for BLCA patients.
PubMed: 38803949
DOI: 10.1016/j.heliyon.2024.e31347 -
Frontiers in Endocrinology 2024Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being... (Review)
Review
The impact of ovarian endometrioma and endometriotic cystectomy on anti-Müllerian hormone, and antral follicle count: a contemporary critical appraisal of systematic reviews.
Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being discussed. Firstly, the effects of endometriotic cystectomy on short and long-term ovarian reserve. Secondly, the accuracy of serum anti-Müllerian hormone (AMH) and antral follicle count (AFC) in estimating ovarian reserve in these cases. Thirdly, the impact of endometrioma itself on the ovarian reserve over time in such cases. The purpose of the present review is to critically assess available systematic reviews and meta-analyses that have explored these questions. Nine eligible reviews were found following a systematic search on PubMed.com and similarly assessed. These reviews varied considerably regarding the level of evidence, as per an identical comprehensive scoring system. Moderate to high-quality evidence demonstrates that endometriotic cystectomy, by the stripping technique, adversely affects ovarian reserve in the short and long term, up to 9-18 months post-surgery. Damage to ovarian reserve was considerable but more pronounced in bilateral cases than unilateral cases, equivalent to 39.5% and 57.0%, respectively. Repeat endometriotic cystectomy is detrimental to ovarian reserve. The impact of endometrioma diameter on ovarian reserve before or after surgery is still unclear. Moderate to high-quality evidence, relying on simultaneous assessment of both ovarian reserve measures, shows that AMH is sensitive while AFC is not in cases undergoing ovarian cystectomy. AMH should be the biomarker of choice for counseling and managing women with endometrioma in their reproductive age, especially before surgery. While there is some evidence to show that endometrioma per se may harm ovarian reserve, this evidence is not robust, and there is good-quality evidence to challenge this notion. It is necessary to conduct further targeted RCTs, systematic reviews, and meta-analyses based on solid methodological grounds to increase the level of evidence, refine quantitative estimates, investigate open questions, and decrease heterogeneity.
Topics: Humans; Female; Endometriosis; Anti-Mullerian Hormone; Ovarian Reserve; Ovarian Follicle; Ovarian Diseases; Systematic Reviews as Topic
PubMed: 38800489
DOI: 10.3389/fendo.2024.1397279 -
Scientific Reports May 2024We aimed to determine if continuous perioperative heart rate variability (HRV) monitoring could improve risk stratification compared to a short preoperative measurement...
We aimed to determine if continuous perioperative heart rate variability (HRV) monitoring could improve risk stratification compared to a short preoperative measurement in radical cystectomy patients. Electrocardiography (ECG) recordings were collected continuously preoperatively to discharge in 83 patients. Two, 5-min ECG signal segments (preoperative and at 24-h post ECG placement) were analyzed offline to extract HRV metrics. HRV metric discriminatory ability to identify patients with 30-day postoperative complications were analyzed using receiver operating characteristics curves. Sixty participants were included for analysis of which 27 (45%) developed a complication within 30 days postoperative. HRV was reduced in patients with complications. Postoperative standard deviation NN intervals and root mean square of successive differences had area under the curves (AUC) of 0.67 (95% CI 0.54 to 0.81) and 0.68 (95% CI 0.54 to 0.82), respectively. Significant discriminatory abilities were also reported for postoperative frequency metrics of absolute low frequency (LF) [AUC = 0.65 (95% CI 0.51 to 0.79)] and high frequency (HF) powers [AUC = 0.69 (95% CI 0.55 to 0.83)] and total power [AUC = 0.66 (95% CI 0.53 to 0.80)]. Postoperative acquired HRV metrics demonstrated improved discriminatory ability. Our findings suggest that longer-term perioperative HRV monitoring presents with superior ability to stratify complication risk.
Topics: Humans; Heart Rate; Postoperative Complications; Male; Female; Aged; Prospective Studies; Middle Aged; Electrocardiography; Urologic Surgical Procedures; Perioperative Period; ROC Curve; Risk Assessment
PubMed: 38796614
DOI: 10.1038/s41598-024-62930-2 -
Current Oncology (Toronto, Ont.) May 2024Muscle-invasive bladder cancer (MIBC) is a potentially fatal disease, especially in the setting of locally advanced or node-positive disease. Adverse outcomes have also...
Muscle-invasive bladder cancer (MIBC) is a potentially fatal disease, especially in the setting of locally advanced or node-positive disease. Adverse outcomes have also primarily been associated with low-income status, as has been reported in other cancers. While the adoption of neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) and pelvic lymph node dissection (PLND) has improved outcomes, these standard-of-care treatments may be underutilized in lower-income patients. We sought to investigate the economic disparities in NAC and PLND receipt and survival outcomes in MIBC. Utilizing the National Cancer Database, a retrospective cohort analysis of cT2-4N0-3M0 BCa patients with urothelial histology who underwent RC was conducted. The impact of income level on overall survival (OS) and the likelihood of receiving NAC and PLND was evaluated. A total of 25,823 patients were included. This study found that lower-income patients were less likely to receive NAC and adequate PLND (≥15 LNs). Moreover, lower-income patients exhibited worse OS (Median OS 55.9 months vs. 68.2 months, < 0.001). Our findings also demonstrated that higher income, treatment at academic facilities, and recent years of diagnosis were associated with an increased likelihood of receiving standard-of-care modalities and improved survival. Even after controlling for clinicodemographic variables, income independently influenced the receipt of standard MIBC treatments and survival. Our findings identify an opportunity to improve the quality of care for lower-income MIBC patients through concerted efforts to regionalize multi-modal urologic oncology care.
Topics: Humans; Urinary Bladder Neoplasms; Lymph Node Excision; Female; Male; Neoadjuvant Therapy; Aged; Middle Aged; Retrospective Studies; Income; Healthcare Disparities; Pelvis; Cystectomy; Neoplasm Invasiveness
PubMed: 38785473
DOI: 10.3390/curroncol31050192 -
Journal of Cancer Immunology 2024Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration-neoadjuvant or...
Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration-neoadjuvant or adjuvant-remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. In addition, a novel murine model of spontaneous metastatic bladder cancer was used to compare the efficacy of neoadjuvant versus adjuvant anti-PD-L1 (αPD-L1) treatment. The clinical trial was closed prematurely due to the industry's withdrawal of drug provision. Adverse events were observed in all patients; however, serious adverse events were not observed in any patient. A complete pathologic response was observed in 50% of the 4 patients enrolled. Response to treatment was significantly associated with elevated urinary T cells including CD8 and IFNγ CD4 T cells, suggesting potential reinforcement of immune responses by neoadjuvant αPD-1 and αCTLA-4 against bladder tumor cells. These findings suggest that combining chemotherapy and immunotherapy in the neoadjuvant setting could be safe. However, the complete response rate of this four-drug regimen was modest and emphasizes the need for randomized controlled trials to properly assess immunotherapy efficacy in the neoadjuvant setting. In corresponding murine studies, the MB49-met model consistently displayed widespread metastasis, including tumor growth in the lungs, liver, and bowel mesentery, within 20 days of subcutaneous transplantation. Mice receiving surgery plus neoadjuvant αPD-L1 or adjuvant αPD-L1 exhibited improved survival compared to those receiving only αPD-L1. However, no significant difference in survival was observed between the neoadjuvant and adjuvant αPD-L1 cohorts. Furthermore, the timing of neoadjuvant therapy administration (early vs. late) did not significantly impact survival. This study highlights the potential of perioperative immunotherapy in the treatment of locally advanced and metastatic bladder cancer.
PubMed: 38784962
DOI: 10.33696/cancerimmunol.6.081 -
Therapeutic Advances in Urology 2024Bladder paraganglioma is a rare neuroendocrine neoplasm, either functional or non-functional, arising from the urinary bladder. Functional variants present with...
Bladder paraganglioma is a rare neuroendocrine neoplasm, either functional or non-functional, arising from the urinary bladder. Functional variants present with catecholamine-related symptoms, while non-functional variants pose diagnostic challenges, mimicking urothelial carcinoma. Misdiagnosis risks underscore the importance of accurate identification for appropriate patient management. In this case, a 52-year-old man, diagnosed incidentally with hypertension and reported occasional post-micturition tachycardia, underwent abdominal ultrasound for known hepatic cyst follow-up, revealing an oval hypoechoic bladder mass. Initial consideration of bladder urothelial carcinoma prompted further investigation with contrast-enhanced CT scan and cystoscopy that confirmed extrinsic mass nature, and subsequent robotic-assisted partial cystectomy was performed. Histologically, the removed mass exhibited characteristic features of bladder paraganglioma. Postoperative recovery was uneventful, with resolution of post-micturition tachycardia at 1 month. Follow-up includes endocrinological evaluation and a 6-month CT scan. In conclusion, bladder paraganglioma should be considered in para-vesical mass differentials. This case highlights the importance of meticulous history collection, even in asymptomatic patients, the need for a multidisciplinary approach for accurate diagnosis and management of this rare condition, and the robotic approach as a viable option.
PubMed: 38779495
DOI: 10.1177/17562872241249603 -
Heliyon May 2024This study aimed to assess the surgical outcomes and identify the conversion risk factors of Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) in...
OBJECTIVE
This study aimed to assess the surgical outcomes and identify the conversion risk factors of Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) in treating ovarian cyst.
METHODS
This was a retrospective study of 505 patients who underwent vNO TES for treating ovarian cyst from March 2019 to February 2022 wherein the patients were classified into "converted" or "nonconverted" groups. T-tests, χ tests, and logistic regression were used for statistical analyses.
RESULTS
There were 16 (3.17 %) surgical conversions and 12 (2.38 %) other surgical complications in our study cohort. Teratomas accounted for 56.8 % of complications in nonconverted cases and 18.8 % in converted cases. Adenocystomas were found in 12.3 % of nonconverted cases and 18.8 % of converted cases. Other types included paraovarian cysts (3.3 % and 0 %), fibroma, granulosa cell tumor, Brenner tumor (1.2 % and 0 %), corpus luteum cysts, follicular cysts (7.6 % and 6.3 %), old abscess (0.2 % and 0 %), and simple cysts (17.6 % and 12.5 %) in the nonconverted and converted groups, respectively. The converted group included more cases of endometriotic cysts (43.8 % vs 12.3 %, p = 0.023), bilateral cysts (37.5 % vs 8.2 %, p < 0.001), severe pelvic adhesion (68.8 % vs 3.3 %, p < 0.001), deep endometriosis (12.5 % vs 0.4 %, p < 0.001), and at least two cysts (37.5 % vs 8.81 %; p < 0.001). Severe pelvic adhesion (adjusted odds ratio [OR], 86.96; range, 18.33-431.77; p < 0.001), bilateral cysts (adjusted OR, 4.75; range, 1.05-21.57, p = 0.043) and endometriotic cysts (adjusted OR, 7.69; range, 3.11-17.08; p < 0.001) were also predictors of surgical conversion.
CONCLUSION
vNOTES demonstrates low complication and conversion rates in treating ovarian cyst compared with TU-LESS. Surgical conversion is associated with severe pelvic adhesions, bilateral cysts, and endometriotic cysts.
PubMed: 38774314
DOI: 10.1016/j.heliyon.2024.e31014