Publications by authors named "Paul Crispen"

Article Synopsis
  • - Paragangliomas (PGL), including urinary bladder paragangliomas (UBPGL), are rare tumors from the autonomic nervous system, with UBPGL making up only 0.7% of PGL and less than 0.05% of bladder tumors.
  • - A case presented a 42-year-old woman with symptoms like menorrhagia and hematuria, who was diagnosed with a UBPGL and a potential myxoma in her heart; a novel mutation linked to the UBPGL was identified as somatic and predicted to impact function.
  • - The report emphasizes the difficulty in diagnosing UBPGLs and shows the importance of a multidisciplinary approach, along with the necessity of
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Purpose: To evaluate the efficacy of intravesical (IVe) Bacillus Calmette-Guerin (BCG) to treat non-muscle invasive bladder cancer (NMIBC) recurrences in patients who have previously undergone nephroureterectomy for upper tract urothelial carcinoma (UTUC).

Methods: We performed a single institution retrospective review of patients who underwent nephroureterectomy for UTUC from 2009 to 2021. Patients who subsequently developed NMIBC treated with transurethral resection followed by IVe BCG were included in the study group.

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Purpose: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.

Materials And Methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50).

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Article Synopsis
  • Hyaluronan (HA) is a key component of the extracellular matrix in tumors, where its synthesis and breakdown are crucial for tumor growth and progression.
  • In cancer, excessive HA production leads to its degradation, resulting in small molecular weight HA fragments that can promote various biological processes, including blood vessel formation and immune suppression.
  • Recent studies focus on the disrupted HA metabolism in urologic cancers like prostate and bladder cancer, suggesting potential new treatment strategies based on these findings.
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EA8212 BRIDGE is a phase 3 randomized trial comparing BCG vs GemDoce for BCG naïve high-risk non-muscle-invasive bladder cancer. This article provides an explanation for the rationale of the clinical trial and details the study design.

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Article Synopsis
  • * In cancer, there tends to be increased production and breakdown of hyaluronan, leading to the buildup of small fragments that promote issues like inflammation, tumor growth, and immune suppression.
  • * The text outlines a method for studying hyaluronan metabolism using precision-cut tissue slice cultures from freshly removed cancer tissue, specifically focusing on human urothelial carcinoma.
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Prostate cancer is the most common solid malignancy in men and requires a biopsy for diagnosis. This manuscript describes a freehand micro-ultrasound guided transperineal technique performed under local anesthesia, which maintains accuracy, keeps patients comfortable, has low adverse events, and minimizes the need for disposables. Prior micro-ultrasound-guided transperineal techniques required general or spinal anesthesia.

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Muscle-invasive bladder cancer is a life-threatening disease best managed with multimodal therapy. Neoadjuvant chemotherapy prior to cystectomy significantly improves survival with the greatest benefit noted in patients with a complete pathologic response noted at cystectomy. While radical cystectomy is currently an important part of the treatment plan, surgical morbidity remains high.

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Article Synopsis
  • PD-L1 expression is often increased in cancer, helping tumors evade the immune system by inhibiting T cells through interaction with the PD1 receptor.
  • *Tumor-associated hyaluronan (HA), produced by tumor cells, plays a key role in promoting the development of immunosuppressive PD-L1 macrophages in the tumor microenvironment.
  • *The study found that clusters of HA-producing fibroblast-like cells and PD-L1 macrophages form in the tumor and its draining lymph nodes, which may contribute to immune escape and decreased effectiveness of immunotherapy.*
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Article Synopsis
  • - RCC patients often have a higher number of immune-suppressing myeloid cells, particularly myeloid-derived suppressor cells (MDSCs), in their blood, which are linked to immune suppression and inflammation.
  • - A study found that untreated RCC patients had increased monocytic MDSCs expressing PD-L1 (linked to immune suppression) and hyaluronidase 2 (Hyal2, linked to inflammation), suggesting they may play a role in both processes.
  • - Analysis of tumor tissue showed the presence of PD-L1 expressing immune cells in the tumor stroma, indicating that the interaction between these myeloid cells and hyaluronan may fuel both inflammation and immune tolerance in kidney cancer. *
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A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders).

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Succinate dehydrogenase (SDH) deficient renal cell carcinoma (RCC) are uncommon renal tumors that typically present in relatively younger patients. SDH mutations are known to cause cancer, but often presents with hereditary paragangliomas, pheochromocytomas, and gastrointestinal stromal tumors. This report details a case of SDH deficient RCC in a patient with no know contributing family history.

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Objective: Acute postoperative pain intensity is associated with persistent postsurgical pain (PPP) risk. However, it remains unclear whether acute postoperative pain intensity mediates the relationship between clinical factors and persistent pain.

Materials And Methods: Participants from a mixed surgical population completed the Brief Pain Inventory and Pain Catastrophizing Scale before surgery, and the Brief Pain Inventory daily after surgery for 7 days and at 30 and 90 days after surgery.

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Introduction And Background: Several features noted on renal mass biopsy (RMB) can influence treatment selection including tumor histology and nuclear grade. However, there is poor concordance between renal cell carcinoma (RCC) nuclear grade on RMB compared to nephrectomy specimens. Here, we evaluate the association of nuclear grade with aorta-lesion-attenuation-difference (ALAD) values determined on preoperative CT scan.

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Objectives: We previously noted that the aorta-lesion-attenuation difference (ALAD) determined on CT scan discriminated well between chromophobe RCC and oncocytoma. The current evaluation seeks to validate these initial findings in a second cohort of nephrectomy patients.

Methods: A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for small, solid renal masses.

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Background: Evidence suggests that increased early postoperative pain (POP) intensities are associated with increased pain in the weeks following surgery. However, it remains unclear which temporal aspects of this early POP relate to later pain experience. In this prospective cohort study, we used wavelet analysis of clinically captured POP intensity data on postoperative days 1 and 2 to characterize slow/fast dynamics of POP intensities and predict pain outcomes on postoperative day 30.

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Background: The primary goal of this study was to evaluate patterns in acute postoperative pain in a mixed surgical patient cohort with the hypothesis that there would be heterogeneity in these patterns.

Methods: This study included 360 patients from a mixed surgical cohort whose pain was measured across postoperative days 1 through 7. Pain was characterized using the Brief Pain Inventory.

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Background: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer.

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The increased presence of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in tumor tissue has been extensively reported. However, their role in the regulation of hyaluronan (HA) metabolism in the tumor microenvironment has not been established. Here we describe a novel function of tumor-associated myeloid cells related to the enhanced breakdown of extracellular HA in human bladder cancer tissue, leading to the accumulation of small HA fragments with molecular weight (MW) <20 kDa.

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Background: Increased acute postoperative pain intensity has been associated with the development of persistent postsurgical pain (PPP) in mechanistic and clinical investigations, but it remains unclear which aspects of acute pain explain this linkage.

Methods: We analysed clinical postoperative pain intensity assessments using symbolic aggregate approximations (SAX), a graphical way of representing changes between pain states from one patient evaluation to the next, to visualize and understand how pain intensity changes across sequential assessments are associated with the intensity of postoperative pain at 1 (M1) and 6 (M6) months after surgery. SAX-based acute pain transition patterns were compared using cosine similarity, which indicates the degree to which patterns mirror each other.

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With the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway).

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Objective: To evaluate the ability of Aorta-Lesion-Attenuation Difference (ALAD) to differentiate malignant renal tumors from renal oncocytomas.

Methods: A retrospective review of preoperative computed tomography (CT) scans and surgical pathology was performed on patients undergoing partial nephrectomy for small, solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan.

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Background: Results of randomized trials support a single dose of intravesical chemotherapy following radical nephroureterectomy (RNU) for urothelial carcinoma.

Objective: To evaluate the impact of the timing of intravesical mitomycin C (MMC) administration on the rate of bladder tumor recurrence (BTR) following RNU.

Methods: We performed a retrospective review of patients who underwent RNU for upper tract urothelial carcinoma (UTUC) and received intravesical MMC between 2008 and 2016.

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Although surgical excision is the standard of therapy for small renal masses (SRMs), there is a growing recognition of active surveillance as an option in select patients who are poor surgical candidates or who have shorter life expectancy. A number of patients on expectant management, however, subsequently advance to definitive therapy. In this study, we systematically reviewed the literature and performed a pooled analysis of active surveillance series to evaluate the rate and indications for definitive treatment after initiating a period of active surveillance.

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