Browsing by Author "Tan, Wei Phin"
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Item Open Access Diet and Exercise Are not Associated with Skeletal Muscle Mass and Sarcopenia in Patients with Bladder Cancer.(European urology oncology, 2021-04) Wang, Yingqi; Chang, Andrew; Tan, Wei Phin; Fantony, Joseph J; Gopalakrishna, Ajay; Barton, Gregory J; Wischmeyer, Paul E; Gupta, Rajan T; Inman, Brant ABackground
There is limited understanding about why sarcopenia is happening in bladder cancer, and which modifiable and nonmodifiable patient-level factors affect its occurrence.Objective
The objective is to determine the extent to which nonmodifiable risk factors, modifiable lifestyle risk factors, or cancer-related factors are determining body composition changes and sarcopenia in bladder cancer survivors.Design, setting, and participants
Patients above 18 yr of age with a histologically confirmed diagnosis of bladder cancer and a history of receiving care at Duke University Medical Center between January 1, 1996 and June 30, 2017 were included in this study.Outcome measurements and statistical analysis
Bladder cancer survivors from our institution were assessed for their dietary intake patterns utilizing the Diet History Questionnaire II (DHQ-II) and physical activity utilizing the International Physical Activity Questionnaire long form (IPAQ-L) tools. Healthy Eating Index 2010 (HEI2010) scores were calculated from DHQ-II results. Body composition was evaluated using Slice-O-Matic computed tomography scan image analysis at L3 level and the skeletal muscle index (SMI) calculated by three independent raters.Results and limitations
A total of 285 patients were evaluated in the study, and the intraclass correlation for smooth muscle area was 0.97 (95% confidence interval: 0.94-0.98) between raters. The proportions of patients who met the definition of sarcopenia were 72% for men and 55% of women. Univariate linear regression analysis demonstrated that older age, male gender, and black race were highly significant predictors of SMI, whereas tumor stage and grade, chemotherapy, and surgical procedures were not predictors of SMI. Multivariate linear regression analysis demonstrated that modifiable lifestyle factors, including total physical activity (p=0.830), strenuousness (high, moderate, and low) of physical activity (p=0.874), individual nutritional components (daily calories, p=0.739; fat, p=0.259; carbohydrates, p=0.983; and protein, p=0.341), and HEI2010 diet quality (p=0.822) were not associated with SMI.Conclusions
Lifestyle factors including diet quality and physical activity are not associated with SMI and therefore appear to have limited impact on sarcopenia. Sarcopenia may largely be affected by nonmodifiable risk factors.Patient summary
In this report, we aim to determine whether lifestyle factors such as diet and physical activity were the primary drivers of body composition changes and sarcopenia in bladder cancer survivors. We found that lifestyle factors including dietary habits, individual nutritional components, and physical activity do not demonstrate an association with skeletal muscle mass, and therefore may have limited impact on sarcopenia.Item Open Access Follicle-Stimulating Hormone (FSH) Levels During Androgen Deprivation Therapy Are Not Associated With Survival or Development of Castration-Resistant Prostate Cancer(Soc Int Urol J) Atchia, Kaleem; Joncas, France-Helene; Trasiewicz, Lily Summers; Tan, Wei Phin; Ding, Keyue; Inman, Brant A; Toren, PaulBackground Follicle-stimulating hormone (FSH) dysregulation plays a potential role in prostate cancer progression. The objective of this study was to evaluate whether higher FSH levels during androgen deprivation therapy (ADT) for recurrent prostate cancer could predict the development of castration-resistant prostate cancer (CRPC), prostate cancer-specific survival (CSS), and overall survival (OS). Methods Serum FSH levels were measured in cryopreserved samples of the continuous ADT arm of the PR.7 trial, supplemented with analogous samples from a large contemporaneous biobank. Univariate and multivariate analyses assessed the relationship between FSH tertiles and time to CRPC, as well as CSS, and OS. Results A total of 172 patients were included in our analysis. Of these, 54 patients (31%) developed CRPC during the 9-year follow-up. Median FSH for the tertiles was 4.35, 6.13, and 11.32 mIU/mL. FSH tertiles were not significantly associated with the time to CRPC, or with CSS or OS. FSH levels were not a significant prognostic factor for these oncologic outcomes. Conclusion As previously reported, the use of gonadotropin-releasing hormone (GnRH) antagonists for ADT has significantly more suppression of FSH levels than GnRH agonists. Our results do not suggest that differences in circulating FSH 1 year following ADT initiation influence long-term oncologic outcomes or development of CRPC.Item Open Access Heated Intravesical Chemotherapy: Biology and Clinical Utility.(The Urologic clinics of North America, 2020-02) Tan, Wei Phin; Longo, Thomas A; Inman, Brant ANon-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment of bladder cancer.Item Open Access Hyperthermia Improves Solubility of Intravesical Chemotherapeutic Agents(Bladder Cancer, 2020-12-14) Grimberg, Dominic; Shah, Ankeet; Tan, Wei Phin; Etienne, Wiguins; Spasojevic, Ivan; Inman, BrantBACKGROUND: Nearly 70% of all new cases of bladder cancer are non-muscle invasive disease, the treatment for which includes transurethral resection followed by intravesical therapy. Unfortunately, recurrence rates approach 50% in part due to poor intravesical drug delivery. Hyperthermia is frequently used as an adjunct to intravesical chemotherapy to improve drug delivery and response to treatment. OBJECTIVE: To assess the solubility profile of intravesical chemotherapies under varying conditions of pH and temperature. METHODS: Using microplate laser nephelometry we measured the solubility of three intravesical chemotherapy agents (mitomycin C, gemcitabine, and cisplatin) at varying physical conditions. Drugs were assessed at room temperature (23°C), body temperature (37°C), and 43°C, the temperature used for hyperthermic intravesical treatments. To account for variations in urine pH, solubility was also investigated at pH 4.00, 6.00, and 8.00. RESULTS: Heat incrementally increased the solubility of all three drugs studied. Conversely, pH largely did not impact solubility aside for gemcitabine which showed slightly reduced solubility at pH 8.00 versus 6.00 or 4.00. Mitomycin C at the commonly used 2.0 mg/mL was insoluble at room temperature, but soluble at both 37 and 43°C. CONCLUSIONS: Hyperthermia as an adjunct to intravesical treatment would improve drug solubility, and likely drug delivery as some current regimens are insoluble without heat. Improvements in solubility also allow for testing of alternative administration regimens to improve drug delivery or tolerability. Further studies are needed to confirm that improvements in solubility result in increased drug delivery.Item Open Access National Quality Improvement Program in Transurethral Resection of Bladder Tumor: A Model for the Rest of Us, Even if We Cannot Share All Results.(European urology, 2020-08-09) Shah, Ankeet; Tan, Wei Phin; Inman, Brant AItem Open Access PD-L1/PD-1 Biomarker for Metastatic Urothelial Cancer that Progress Post-platinum Therapy: A Systematic Review and Meta-analysis.(Bladder cancer (Amsterdam, Netherlands), 2019-11-22) Tan, Wei Phin; Tan, Wei Shen; Inman, Brant ABackground
Immune checkpoint inhibitors (ICI) are extremely expensive and most patients with metastatic urothelial carcinoma (mUC) do not benefit significantly from their use.Objective
We performed a systematic review and meta-analysis to determine response rates and survival outcomes on patients with mUC progressing despite prior platinum-based chemotherapy receiving ICI stratified by biomarker status.Methods
We performed a comprehensive literature search for all articles in PubMed and Embase up to 06/15/2019 to identify all studies pertaining to programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) receptor targeted therapies for mUC that reported biomarkers. Given that biomarkers are reported on different scales and with different metrics, we defined each biomarker as either positive or negative using the definitions implemented in each individual trial. We meta-analyzed the data, reconstructed overall (OS) and progression-free survival (PFS) curves, and analyzed response rates by biomarker status. OS and PFS were analyzed in a pooled Kaplan-Meier analysis and pseudo-individualized patient data (IPD) extracted.Results
We identified 1429 manuscripts of which 8 met inclusion criteria, with a total of 1837 treated patients with outcomes data. On proportional hazards survival analysis, patients in the biomarker negative group were associated with a lower PFS (HR 1.48, 95% CI: 1.18 - 1.85, p < 0.001) and lower OS (HR 1.54, 95% CI: 1.32 - 1.80, p < 0.001) when compared to the biomarker positive group. Response data was available for 1641 patients and random effects proportion show complete response in 8% and 3% in biomarker positive and negative patients, respectively.Conclusions
ICI therapy for metastatic UC post platinum therapy has a higher overall response rate, OS and PFS in patients who are biomarker positive compared to those who are negative. However, some patients who are biomarker negative do achieve complete responses. A better biomarker for patient selection is essential before biomarkers can be used to stratify candidates for ICI therapy.Item Open Access Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.(International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2020-01) Tan, Wei Phin; Chang, Andrew; Brousell, Steven C; Grimberg, Dominic C; Fantony, Joseph J; Longo, Thomas A; Etienne, Wiguins; Spasojevic, Ivan; Maccarini, Paolo; Inman, Brant ABackground
Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity.Objective
To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS).Methods
Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry.Results
The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose.Conclusions
Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.Item Open Access The nephroureterectomy: a review of technique and current controversies.(Translational andrology and urology, 2020-12) Barton, Gregory J; Tan, Wei Phin; Inman, Brant AThe nephroureterectomy (NU) is the standard of care for invasive upper tract urothelial carcinoma (UTUC) and has been around for well over one hundred years. Since then new operative techniques have emerged, new technologies have developed, and the surgery continues to evolve and grow. In this article, we review the various surgical techniques, as well as present the literature surrounding current areas of debate surrounding the NU, including the lymphatic drainage of the upper urinary tract, management of UTUC involvement with the adrenals and caval thrombi, surgical management of the distal ureter, the use of intravesical chemotherapy as well as perioperative systemic chemotherapy, as well as various outcome measures. Although much has been studied about the NU, there still is a dearth of level 1 evidence and the field would benefit from further studies.