Metastasis-Directed Therapy for Oligometastatic Castration-Sensitive Prostate Cancer: An Alternative to ADT?

PURPOSE OF REVIEW: The standard treatment of patients with metastatic prostate cancer is systemic treatment with androgen-deprivation therapy (ADT). The spectrum-based model of metastatic disease includes the presence of an oligometastatic state, an intermediary between localized and widespread metastatic disease, in which radical local treatment might improve systemic control. Our purpose is to review the literature on metastasis-directed therapy in the treatment of oligometastatic prostate cancer. RECENT FINDINGS: Several prospective clinical trials have reported improvements in ADT-free survival and progression-free survival with metastasis-directed therapy of oligometastatic prostate cancer. Retrospective studies have found improvements in oncologic outcomes for patients with oligometastatic prostate cancer undergoing metastasis-directed therapy, and several recent prospective clinical trials have confirmed these results. Advancements in imaging as well as an understanding of the genomics of oligometastatic prostate cancer may allow for better patient selection for metastasis-directed therapy and the potential for cure in selected patients.

Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery.

Microneedles have recently been adopted for use as a painless and safe method of transdermal therapeutic delivery through physically permeating the stratum corneum. While microneedles create pathways to introduce drugs, they can also act as conduits for biosignal sensing. Here, we explore the development of microneedles as both biosensing and drug delivery platforms. Microneedle sensors are being developed for continuous monitoring of biopotentials and bioanalytes through the use of conductive and electrochemically reactive biomaterials. The range of therapeutics being delivered through microneedle devices has diversified, while novel bioabsorbable microneedles are undergoing first-in-human clinical studies. We foresee that future microneedle platform development will focus on the incorporation of biofunctional materials, designed to deliver therapeutics in a stimulus responsive fashion. Biofunctional microneedle patches will require improved methods of attaching to and conforming to epithelial tissues in dynamic environments for longer periods of time and thus present an assortment of new design challenges. Through the evolution of biomaterial development and microneedle design, biofunctional microneedles are proposed as a next generation of stimulus responsive drug delivery systems.

Smoking is not associated with wound complications in augmented urethroplasty: a NSQIP analysis.

OBJECTIVE: To investigate if predictors of wound complications differed between patients undergoing excision and primary anastomosis urethroplasty (EPA) and augmented urethroplasty. METHODS: The National Surgical Quality Improvement Program database from 2006 to 2018 was queried for male patients undergoing urethroplasty. Thirty-day wound complications were identified and categorized (superficial/deep/organ-space surgical site infections and dehiscence). Multivariable logistic regression was performed to determine risk factors associated with wound complications. Smoking history was defined as current smoker within the past year. RESULTS: Urethroplasty was performed in 2251 males, with 25.46% (n = 573) using a flap or graft. There was no significant difference in wound complications for patients undergoing augmented urethroplasty (n = 17, 2.97%) or EPA (n = 45, 2.68%) (p = 0.9). The augmented group had a higher BMI, longer operative time, and longer length of stay. On multivariable logistic regression, risk factors associated with wound complications for patients undergoing EPA were diabetes (OR 2.56, p = 0.03) and smoking (OR 2.32, p = 0.02). However, these factors were not associated with wound complications in patients undergoing augmented urethroplasty. CONCLUSIONS: Smoking and diabetes were associated with increased wound complications for men undergoing EPA, but not in patients undergoing augmented urethroplasty. Patients with comorbidities associated with worse wound healing may be more likely to have a wound complication when undergoing EPA.

Feasibility and safety of the da Vinci Xi surgical robot for transoral robotic surgery.

The collective experience supporting the safety and efficacy of transoral robotic surgery continues to grow. The surgical robot da Vinci Xi has been used successfully off-label for head and neck surgery, including transoral robotic surgery. We evaluated operative outcomes and efficacy of the da Vinci Xi surgical robot for transoral surgery and compared our experience with the da Vinci Si and published da Vinci Xi experiences in transoral surgery. Nineteen total cases were retrospectively reviewed, six with the Si and thirteen with the Xi. Our experience with the da Vinci Xi showed similar peri- and postoperative outcomes to our Si experience the available da Vinci Xi literature. We advocate for careful patient selection while also considering the surgical team's experience with TORS. Transoral robotic surgery with the da Vinci Xi has specific advantages, and support is accumulating for its use in TORS. However, this indication remains off-label, and we do not anticipate the manufacturer will seek approval for this indication given the ongoing development and regulatory approvals of da Vinci Single Port for similar indications.

The Effectiveness of a Journal Club for Improving Evidence-Based Medicine Skills and Confidence in Pre-clerkship Medical Students.

Introduction: Evidence-based medicine (EBM) refers to medical practice that uses current best evidence to inform decision-making. This requires several skills including (1) creating an answerable question, (2) searching literature, (3) critically appraising evidence, and (4) applying results. Journal clubs are known to be effective in improving searching and critical appraisal skills in graduate medical education. In pre-clerkship medical education, journal clubs are used less often, and students often do not have the opportunity to engage in all of the steps above. Methods: We developed a journal club for pre-clerkship students and measured its effectiveness using a pre-test, post-test design. Students attended 5 journal club sessions run by rotating student leaders and facilitated by faculty. Student groups developed searchable questions from clinical cases, searched the literature, located and critically appraised an article, and applied results to the case. We measured EBM skills and confidence using two validated questionnaires. Results: Twenty-nine students (MS-1 and MS-2) completed the study. EBM confidence significantly improved at post-test with greatest improvements in the MS-1 student cohort. Confidence in developing a searchable question from a patient case significantly improved in both cohorts. There were no changes measured on the Test of EBM Knowledge and Skills. Discussion: Participation in a faculty-mentored, student-led journal club improved confidence across all domains of EBM, primarily in MS-1 students. Journal clubs are positively received by pre-clerkship medical students and provide effective mechanisms to teach and promote all steps of EBM in pre-clerkship curricula. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01779-y.

Assessing Radiology Practice Patterns for Obtaining MRI in Pediatric Patients with MR-Conditional Tracheostomy Tubes.

OBJECTIVES: Silicone tracheostomy tubes are a popular choice for pediatric patients with chronic tracheostomies due to their pliability and increased comfort. However, the presence of wire reinforcement causes them to be labeled "MR-conditional." The objective of this study was to understand practice patterns across radiology departments for obtaining MRI in children with MR-conditional tracheostomy tubes. METHODS: A survey consisting of 7 questions aimed at determining a facility's protocol for obtaining MRI in children with tracheostomy tubes was developed and administered via telephone to MRI technologists at US children's hospitals. RESULTS: 182 children's hospitals were identified and 59 responses were obtained across 30 states (32.4%). 19 sites (32%) were excluded as they were unable to perform MRI. All 40 facilities reported that they have a standard questionnaire for medical implants, however only 20 reported that tracheostomy tubes are included on that questionnaire (50%). 6 (15%) reported all MR-conditional tubes are changed to MR-safe ones. Of the remaining 34, protocols were as follows: 1 (2.9%) scans patients with conditional tubes for a maximum of 15 minutes, 5 (14.7%) only use a 1.5T magnet, and 28 (82.3%) reported following the manufacturer conditions. In terms of artifact, 3 sites change MR-conditional tubes to MR-safe if scanning the head, neck, chest, or abdomen (8.8%), 6 (17.6%) change the tube if scanning the head or neck, 15 (44.1%) change the tube only if scanning the neck, and 10 (29.4%) were not aware of issues with artifact. CONCLUSION: Based on this survey of MRI technologists at US children's hospitals, there is no unified protocol for obtaining MRI in pediatric patients with MR-conditional tracheostomy tubes. A lack of standardized protocols may be contributing to unnecessary tracheostomy changes. Future research includes clearly defining the anatomical regions affected by wire-related artifact and developing a standardized MRI protocol for these patients.

The use of blue-light cystoscopy in the detection and surveillance of nonmuscle invasive bladder cancer.

Nonmuscle invasive bladder cancer is associated with a high risk of recurrence as well as progression to muscle-invasive disease. Therefore, adequate visualization and identification of malignant lesions as well as complete resection are critical. Traditional white-light cystoscopy is limited in its ability to detect bladder cancer, specifically carcinoma in situ. Blue-light cystoscopy makes use of the intravesical instillation of a heme precursor to differentiate areas of malignancy from normal tissue. A narrative review of the literature on the use of blue-light cystoscopy in bladder cancer was conducted. Blue-light cystoscopy has been shown in several randomized clinical trials to increase detection of Ta, T1, and carcinoma in situ, as well as reduce risk of recurrence at 12 months as compared with traditional white-light cystoscopy. Research into the effects of blue-light cystoscopy on risk of disease progression has produced mixed results, in part due to changing definitions of progression. However, more recent research suggests a correlation with decreased risk of progression. Whereas the use of blue-light was initially limited to rigid cystoscopy in the operating room, results from a recent randomized clinical trial showing enhanced detection of recurrent disease using blue-light in-office surveillance flexible cystoscopy have led to expanded Food and Drug Administration approval. Overall, blue-light cystoscopy offers promise as an enhancement to white-light cystoscopy for the detection of nonmuscle invasive bladder cancer and may yield additional benefits in reducing disease recurrence and progression. Further prospective research is needed to evaluate the true benefit of blue-light cystoscopy in terms of disease progression as well as the cost-effectiveness of this technique.

Renal Cell Carcinoma with Cardiac Metastases: A Case Report and Review of the Literature.

Cardiac metastases from renal cell carcinoma (RCC) are very rare. We describe the case of a woman with RCC with cardiac metastases involving the entire right atrium, penetrating through the myocardium, with extension into the tricuspid valve and right ventricle. This report highlights the unique challenge of the diagnosis and treatment of cardiac metastases in RCC.

Assessment of Resident Knowledge in Pediatric Rheumatology.

Pediatric Rheumatic illnesses are complex, chronic, and often multi-systemic. Our goal was to assess the efficacy of 2 standardized pediatric rheumatology lectures, administered to pediatric residents, in improving the pediatric residents' knowledge and confidence in pediatric rheumatology. Two lectures, 1 hour each, were delivered by 2 residents and given 1 week apart to 28 pediatric residents. Pre- and post-tests assessed knowledge and residents' self-rated competence. Change in knowledge was assessed using paired t-tests. Twenty-eight residents participated in the study. Sixty-three percent (17/27) had an improvement in score from pre-test to post-test. Thirty-seven percent (10/27) reported increased competence from pre-test to post-test. Ninety-six percent (22/23) of the residents found the lectures to be beneficial. Residents in the third post-graduate year (PGY3) cohort had the most significant improvement in scores. The lectures given to the pediatric residents increased pediatric knowledge and the pediatric residents found these lectures to be beneficial.

Metallic microneedles with interconnected porosity: A scalable platform for biosensing and drug delivery.

Metallic-based microneedles (MNs) offer a robust platform for minimally invasive drug delivery and biosensing applications due to their mechanical strength and proven tissue and drug compatibility. However, current designs suffer from limited functional surface area or challenges in manufacturing scalability. Here, porous 316L stainless steel MN patches are proposed. Fabricated through a scalable manufacturing process, they are suitable for storage and delivery of drugs and rapid absorption of fluids for biosensing. Fabrication of these MNs involves hot embossing a patch of stainless steel-based feedstock, sintering at 1100 °C and subsequent electropolishing. Optimisation of this manufacturing process yields devices that maintain mechanical integrity yet possess high surface area and associated porosity (36%) to maximise loading capacity. Similarly, a small pore size has been targeted (average diameter 2.22 µm, with 90% between 1.56 µm and 2.93 µm) to maximise capillarity and loading efficiency. This porous network has a theoretical wicking rate of 4.7 µl/s and can wick-up 27 ±â€¯5 µl of fluid through capillary action which allows for absorption of pharmaceuticals for delivery. When inserted into a metabolite-loaded skin model, the MNs absorbed and recovered 17 ±â€¯3 µl of the metabolite solution. The drug delivery performance of the porous metallic MNs (22.4 ±â€¯4.9 µg/cm2) was found to be threefold higher than that of topical administration (7.1 ±â€¯4.3 µg/cm2). The porous metallic MN patches have been shown to insert into porcine skin under a 19 N load. These results indicate the potential of design-for-manufacturing porous stainless steel MNs in biosensing and drug delivery applications. STATEMENT OF SIGNIFICANCE: Microneedles are micro-scale sharp protrusions used to bypass the stratum corneum, the skin's outer protective layer, and painlessly access dermal layers suitable for drug delivery and biosensing. Despite a depth of research in the area we have not yet seen large-scale clinical adoption of microneedle devices. Here we describe a device designed to address the potential barriers to adoption seen by other microneedles devices. We have developed a scalable, cost effective process to produce medical grade stainless steel microneedle patches which passively absorb and store drugs or interstitial fluid though a porous network and capillary action. This device, with low manufacturing and regulatory burdens may help the large-scale adoption of microneedles.