Comparison of robotic-assisted laparoscopic radical prostatectomy: SP versus XI, a single surgeon experience.

Currently, there is a paucity of data regarding Single Port (SP) robotic-assisted laparoscopic prostatectomy (RALP). Our objective was to compare our single-institution single-surgeon SP RALP experience to our XI RALP experience with regard to patient selection, perioperative data, and outcomes. Patients who underwent prostatectomy at our institution between August 2019 and April 2021 were selected for analysis. All patients had biopsy confirmed prostate cancer. All surgeries were performed by one urologist at our institution to limit inter-surgeon variability. Demographic and clinical information were extracted from the medical record in standardized fashion. All documented classifications were graded using the Clavien-Dindo classification system. Patients with previous prostate cancer therapies were excluded. Categorical variables were compared using Chi-square or Fisher's exact test where appropriate. Continuous variables were compared using t tests or Wilcoxon rank sum tests where appropriate. Complete records were available for 208 patients. Of the total patient population 127 (61.1%) underwent SP prostatectomy compared to 81 (38.9%) underwent XI prostatectomy. There was no significant difference between the two cohorts in terms of mean age (65 vs. 66 years; p = 0.60), BMI (29.2 vs. 30.1; p = 0.22), preop ASA score ≥ 3 (68.5% vs. 64.2%; p = 0.52), or preop PSA (7.1 vs. 7.4, p = 0.94). There no difference in procedure time for SP prostatectomy (170 vs. 168 min, p = 0.035), estimated blood loss (100 vs. 100 mL; p = 0.14), or average length of stay (1 vs. 1 days; p = 0.22). There was a significant difference in Gleason grade group between the two cohorts with patients undergoing XI RALRP more likely to have higher stage disease (p = 0.025) and a trend towards higher D'Amico risk scores in the XI group (p = 0.053). There was no difference in rate of positive surgical margins (29.9% vs. 29.6%; p = 0.96). There was no difference in the distribution of complications between the two groups (p = 0.99) with 89% of patients having no complication. There was no difference in the number of lymph nodes removed by modality (p = 0.94). To date, this study represents one of the largest cohorts of patients who underwent SP RALP. Importantly, it is among the first studies comparing perioperative variables between the SP and XI platforms. As surgeons become more facile with the SP system there appear to minimal differences in patient factors, perioperative results, or outcomes between the platforms. These findings provide evidence that surgeons who are competent on the XI platform can confidently perform SP RALPs through a single incision without compromising outcomes.

A numerical investigation of the hydrodynamic dispersion in triply periodic chromatographic stationary phases.

3D printed custom chromatographic stationary phases have recently been demonstrated. Using the Lattice Boltzmann Method, we compared the model-predicted chromatographic performance of random packing of monodisperse spheres, open tubular columns (OTC) and stationary phases based on three triply periodic minimal surfaces (TPMS): Schwarz Diamond (SD), Schoen Gyroid (SG) and Schwarz Primitive (SP). Three performance metrics were employed in this comparison: i) reduced plate height, ii) Darcy number, iii) kinetic performance factor. Each simulated geometry was unconfined with an impermeable stationary phase to remove wall effects and pore diffusion. The performance was studied for macro-porosities in the range 0.2 to 0.8, depending on the geometry. OTCs were found to have superior permeability to both random sphere packing and TPMS structures across the entire porosity range. At porosity greater than 0.366, the Schwarz Diamond medium achieved the lowest levels of band broadening and greatest kinetic performance. The reduced plate height of all stationary phase geometries was shown to increase with bed porosity. The kinetic performance was found to increase with porosity for TPMS structures, decrease with porosity for random packing and be independent of porosity for OTCs. This work illustrates that chromatographic stationary phase geometries based on TPMS structures are theoretically competitive with random packing and open tubular columns and their feasibility for practical chromatography should continue to be explored.

Barriers and facilitators to diabetic retinopathy screening within Australian primary care.

BACKGROUND: Despite recent incentives through Medicare (Australia's universal health insurance scheme) to increase retinal screening rates in primary care, comprehensive diabetic retinopathy (DR) screening has not been reached in Australia. The current study aimed to identify key factors affecting the delivery of diabetic retinopathy (DR) screening in Australian general practices. METHODS: A descriptive qualitative study involving in-depth interviews was carried out from November 2019 to March 2020. Using purposive snowballing sampling, 15 general practitioners (GPs) were recruited from urban and rural general practices in New South Wales and Western Australia. A semi-structured interview guide was used to collect data from participants. All interviews were conducted over the phone by one facilitator, and each interview lasted up to 45 min. The Socio-Ecological Model was used to inform the content of the interview topic guides and subsequent data analysis. Recorded data were transcribed verbatim, and thematic analysis was conducted to identify and classify recurrent themes. RESULTS: Of 15 GPs interviewed, 13 were male doctors, and the mean age was 54.7 ± 15.5 years. Seven participants were practising in urban areas, while eight were practising in regional or remote areas. All participants had access to a direct ophthalmoscope, but none owned retinal cameras. None of the participants reported performing DR screening. Only three participants were aware of the Medicare Benefits Schedule (MBS) items 12,325 and 12,326 that allow GPs to bill for retinal screening. Seven themes, a combination of facilitators and barriers, emerged from interviews with the GPs. Despite the strong belief in their role in managing chronic diseases, barriers such as costs of retinal cameras, time constraints, lack of skills to make DR diagnosis, and unawareness of Medicare incentives for non-mydriatic retinal photography made it difficult to conduct DR screening in general practice. However, several enabling strategies to deliver DR screening within primary care include increasing GPs' access to continuing professional development, subsidising the cost of retinal cameras, and the need for a champion ace to take the responsibility of retinal photography. CONCLUSION: This study identified essential areas at the system level that require addressing to promote the broader implementation of DR screening, in particular, a nationwide awareness campaign to maximise the use of MBS items, improve GPs' competency, and subsidise costs of the retinal cameras for small and rural general practices.

Pure Robotic-assisted Level IV Inferior Vena Cava Thrombectomy for Angiomyolipoma Without Cardiopulmonary Bypass: A First Report.

OBJECTIVE: To report the initial case of robotic-assisted level IV inferior vena cava (IVC) tumor thrombectomy, with the supra- and infradiaphragmatic caval segments managed purely by a robotic-assisted technique. METHODS: A 67-year-old female presented with a 5.3 × 2.4 cm right renal tumor and a level IV IVC tumor thrombus, 16.5 cm in length, extending 1.5 cm into the right atrium. Through a robotic trans-abdominal approach, the infrarenal and retrohepatic IVC, left renal vein and right kidney were secured. Using a robotic transthoracic approach, the thrombus was milked out of the right atrium. The intrapericardial caval segment was secured and the right atrium was excluded. No cardiopulmonary bypass was used. A cavotomy was made at the right renal vein os and the tumor thrombus was extracted en bloc in a retrograde manner under transesophageal echocardiographic visualization. RESULTS: Total operative time was 211 minutes, including robotic docking, with 90 minutes spent on taking down intraabdominal adhesions. Caval clamp time was 13 minutes. Estimated blood loss was 100 mL. Postoperatively, the patient developed atrial fibrillation with rapid ventricular rate (RVR) requiring diltiazem infusion (Clavien Grade II). Hospital stay was 5 days. There were no further complications. Pathology revealed an Angiomyolipoma and negative surgical margins. CONCLUSION: This is the initial report of a purely robotic-assisted level IV IVC tumor thrombectomy. We used this technique for an angiomyolipoma with tumor thrombus extending 1.5cm into the right atrium, managing both the supra- and infradiaphragmatic caval segments robotically. This report further extends the field of robotic surgery.

Decreasing the prospect of upper extremity neuropraxia during robotic assisted laparoscopic prostatectomy: a novel technique.

Risk of intraoperative neuropathic injury in minimally invasive surgery has been established as a leading complication. Continuous intraoperative neuromonitoring (IONM), such as upper extremity somatosensory evoked potentials (ueSSEPs), to decrease peripheral nerve injury due to positional stress has been described. Robotic-assisted laparoscopic prostatectomy (RALP) requires steep Trendelenberg, which may predispose patients to upper extremity neuropraxia. Subdermal stimulating electrodes were placed on the patients' bilateral wrists over the ulnar nerve and the nerve was stimulated. Realtime waveforms were compared to baseline data to prevent and detect injury to the ulnar nerve. Established intervention criteria, indicating risk for neuropathic damage necessitating intraoperative patient repositioning, was a 50% loss in amplitude or a 10% increase in latency. One hundred and forty three patients received RALP with IONM. 17 of 143 patients (11.8%) met ueSSEP intervention criteria. Only weight was significantly different between the two groups (p = 0.04). Mean reduction in amplitude was 79.9% (SE 4.1). Average amplitude loss duration was 22 min (SE 4.0). Weight and BMI were correlated to the degree of amplitude reduction (p = 0.03 and < 0.01), while operative time and DM approached significance (p = 0.09 and p = 0.14). This is the first study to use IONM to reduce the risk of nerve injury during genitourinary surgery. Realtime nerve monitoring using ueSSEP allowed for upper extremity intraoperative monitoring and repositioning. This may decrease the risk of upper extremity neuropraxia due to malpositioning during RALP. Weight and BMI were identified as risk factors for possible nerve injury. Further data collection and analysis to preoperatively stratify patients for application of IONM during RALP is currently ongoing.

Robotic level II inferior vena cava thrombectomy for metastatic melanoma.

We report on a case of a 38-year-old female who presented with metastatic malignant melanoma of her right kidney with Level II tumor thrombus. This is the first ever presented case of a renal melanoma IVC tumor thrombus. Furthermore, in an effort to expand the surgical scope of minimally invasive and robotic surgery, we report management of this lesion as the first case of non-renal cell carcinoma IVC tumor thrombus treated with a robotic thrombectomy.

"Balancing" balancing selection? Assortative mating at the major histocompatibility complex despite molecular signatures of balancing selection.

In vertebrate animals, genes of the major histocompatibility complex (MHC) determine the set of pathogens to which an individual's adaptive immune system can respond. MHC genes are extraordinarily polymorphic, often showing elevated nonsynonymous relative to synonymous sequence variation and sharing presumably ancient polymorphisms between lineages. These patterns likely reflect pathogen-mediated balancing selection, for example, rare-allele or heterozygote advantage. Such selection is often reinforced by disassortative mating at MHC. We characterized exon 2 of MHC class II, corresponding to the hypervariable peptide-binding region, in song sparrows (Melospiza melodia). We compared nonsynonymous to synonymous sequence variation in order to identify positively selected sites; assessed evidence for trans-species polymorphisms indicating ancient balancing selection; and compared MHC similarity of socially mated pairs to expectations under random mating. Six codons showed elevated ratios of nonsynonymous to synonymous variation, consistent with balancing selection, and we characterized several alleles similar to those occurring in at least four other avian families. Despite this evidence for historical balancing selection, mated pairs were significantly more similar at MHC than were randomly generated pairings. Nonrandom mating at MHC thus appears to partially counteract, not reinforce, pathogen-mediated balancing selection in this system. We suggest that in systems where individual fitness does not increase monotonically with MHC diversity, assortative mating may help to avoid excessive offspring heterozygosity that could otherwise arise from long-standing balancing selection.

Fusion prostate biopsy outperforms 12-core systematic prostate biopsy in patients with prior negative systematic biopsy: A multi-institutional analysis.

INTRODUCTION AND OBJECTIVES: Patients with persistently elevated prostate specific antigen (PSA) and prior negative 12-core TRUS prostate biopsy (or biopsies) (systematic biopsy-SBx) are a diagnostic challenge. Repeat SBx or saturation biopsy in this cohort has been shown to have an even lower yield. The aim of our study is to compare the prostate cancer yield of magnetic resonance imaging (MRI) fusion biopsy (FBx) to SBx in a multi-institutional cohort comprised of patients with prior negative biopsies. METHODS: A multi-institutional review was performed on patients with a history of one or more prior negative SBx who underwent multiparametric MRI (mpMRI), followed by FBx and SBx in the same session. Imaging protocol was standardized across institutions and institutional genitourinary radiologists and pathologists reviewed mpMRI and pathology, respectively. Gleason score (GS) distribution and risk classifications were recorded. Prostate cancer with GS ≥3 + 4 was defined as clinically significant (CS). Univariate and multivariable logistic regression was done to identify predictors of cancer detection on SBx and FBx. RESULTS: Seven-hundred seventy-nine patients from four institutions were included in the study. Median age and prostate specific antigen (IQR) were 63.1 (58.5-68.0) years and 8.5 (5.9-13.1)ng/dl, respectively. Median number of prior negative biopsies (range) was 2.0 (1-16). The cancer detection rate (CDR) in the cohort was 346/779 patients (44.4%). Total CS CDR was 30.7% (239/779 patients), with FBx detecting 26.3% (205/779) of patients with CS disease and SBx diagnosing an additional 4.4% (34/779) of patients (P<0.001). Furthermore, of all cancers detected by each modality, FBx detected a higher proportion of CS cancer compared to SBx (one negative biopsy: 75 vs. 50%, P<0.001, 2-3 negative biopsy: 76 vs. 61%, P = 0.006, 4 or more negative biopsies: 84 vs. 52%, P = 0.006). As such, SBx added a relatively small diagnostic value to FBx for detecting CS disease (one negative biopsy 3.5%, 2-3 negative biopsies 5%, 4 or more negative biopsies: 1%). FBx also outperformed SBx for upgrading patients to an intermediate or high-risk cancer category (GS>6) (one negative biopsy 11.5% vs. 3.6%, 2-3 negative biopsy 10.3% vs. 5.3%, 4 or more negative biopsies 19.1% vs. 1.1%). On multivariable analysis, the number of prior negative biopsies was a significant negative predictor of CS CDR on SBx (P = 0.006), but not on FBx (P = 0.151). CONCLUSIONS: Using a large multi-institutional cohort, we were able to demonstrate that FBx outperformed SBx in patients with prior negative systematic biopsy. This was due, in part, to the decreasing CS CDR by SBx with increased number of prior biopsies. The yield of FBx stayed constant and did not decrease with increased number of prior negative biopsies. Therefore, repeat SBx alone in patients with multiple prior negative biopsies will be hindered by lower yield and FBx should be utilized concurrently in these patients.

Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling, in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small-molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with Hsp40. Pull-down studies using biotinylated-C86 found Hsp40 present in a multiprotein complex with full-length (FL-) AR, ARv7, and Hsp70 in CRPC cells. Treatment of CRPC cells with C86 or the allosteric Hsp70 inhibitor JG98 resulted in rapid protein destabilization of both FL-AR and ARv, including ARv7, concomitant with reduced FL-AR- and ARv7-mediated transcriptional activity. The glucocorticoid receptor, whose elevated expression in a subset of CRPC also leads to androgen-independent AR target gene transcription, was also destabilized by inhibition of Hsp40 or Hsp70. In vivo, Hsp40 or Hsp70 inhibition demonstrated single-agent and combinatorial activity in a 22Rv1 CRPC xenograft model. These data reveal that, in addition to recognized roles of Hsp40 and Hsp70 in FL-AR LBD remodeling, ARv lacking the LBD remain dependent on molecular chaperones for stability and function. Our findings highlight the feasibility and potential benefit of targeting the Hsp40/Hsp70 chaperone axis to treat prostate cancer that has become resistant to standard antiandrogen therapy.Significance: These findings highlight the feasibility of targeting the Hsp40/Hsp70 chaperone axis to treat CRPC that has become resistant to standard antiandrogen therapy. Cancer Res; 78(14); 4022-35. ©2018 AACR.

Using Imaging to Predict Treatment Response in Genitourinary Malignancies.

CONTEXT: Over the previous2 decades, there have been numerous advancements in the diagnostic evaluation, therapeutic management, and postoperative assessment of genitourinary malignancies. OBJECTIVE: To present a review of current and novel imaging modalities and their utility in the assessment of therapeutic response in the systemic management of renal, testicular, and prostate cancers. EVIDENCE ACQUISITION: A PubMed/Medline search of the current published literature inclusive of prospective and retrospective original research, systematic reviews, and meta-analyses was conducted evaluating imaging modalities for renal cell carcinoma, prostate cancer, and testicular cancer. All relevant literature was individually reviewed and summarized to provide a concise description of the currently available imaging modalities and their efficacy in assessing treatment response of the genitourinary malignancies targeted in this review. EVIDENCE SYNTHESIS: Conventional imaging techniques play a pivotal role in predicting the treatment response of genitourinary malignancies and have, therefore, been incorporated into clinical guidelines. Advancements in imaging technology have led to increased utilization for prognostication of a genitourinary cancer's response to therapy. CONCLUSIONS: A good understanding of current recommended imaging techniques to evaluate treatment response in genitourinary malignancies is of paramount importance for today's clinician, who faces increasing treatment modalities. PATIENT SUMMARY: In this review, we summarize available imaging modalities in the evaluation of treatment response in kidney, prostate, or testicular tumors. We believe that a good understanding of current imaging modalities is of paramount importance for healthcare providers treating these cancers.

Repeat Robotic Partial Nephrectomy: Characteristics, Complications, and Renal Functional Outcomes.

INTRODUCTION: Multifocal and hereditary kidney cancers often require repeated ipsilateral nephron sparing procedures with higher blood loss and complication rates compared to first time renal surgery. Consequently, many surgeons avoid minimally invasive techniques in the setting. We present the characteristics, complications, and short-term renal functional outcomes of patients who underwent a repeat robotic partial nephrectomy (rRPNx). MATERIALS AND METHODS: A database was retrospectively reviewed to identify patients who underwent robotic partial nephrectomies between January 2007 and December 2013. Selection criteria for the rRPNx cohort included patients who had undergone at least two ipsilateral renal surgeries, with the second procedure being an rRPNx. All other patients comprised the initial robotic partial nephrectomy (iRPNx) group. RESULTS: One hundred twenty-four patients who underwent robotic partial nephrectomy during the study period were identified. rRPNx constituted 26 (21%) of the total cases. Age of the rRPNx cohort was similar (p = 0.56), but number of tumors resected was two-fold greater in the rRPNx group (p = 0.44). Neither surgery time nor renal clamp time was significantly longer in either group (p = 0.18 and p = 0.65, respectively). Importantly, estimated blood loss (EBL) was significantly larger than in the iRPNx group (p = 0.01). Both groups had similar intravenous pain medication administration durations (p = 0.32), but postsurgical length of stay was greater for the rRPNx patients (p = 0.011). There were no significant differences in clavian complication rates (p = 0.17-0.39), with the exception of urine leak which occurred more frequently in the rRPNx group (p = 0.01). There was no difference in percent change in serum creatinine or estimated glomerular filtration rate (p = 0.89 and p = 0.67, respectively). CONCLUSIONS: rRPNx is safe and feasible in select patients. EBL, postoperative lengths of stay, and urine leak were the only factors significantly associated with rRPNx compared to iRPNx. Patient 3-month follow-up revealed excellent and comparable outcomes between the two groups.

Risk stratification of prostate cancer: integrating multiparametric MRI, nomograms and biomarkers.

Accurate risk stratification of prostate cancer is achieved with a number of existing tools to ensure the identification of at-risk patients, characterization of disease aggressiveness, prediction of cancer burden and extrapolation of treatment outcomes for appropriate management of the disease. Statistical tables and nomograms using classic clinicopathological variables have long been the standard of care. However, the introduction of multiparametric MRI, along with fusion-guided targeted prostate biopsy and novel biomarkers, are being assimilated into clinical practice. The majority of studies to date present the outcomes of each in isolation. The current review offers a critical and objective assessment regarding the integration of multiparametric MRI and fusion-guided prostate biopsy with novel biomarkers and predictive nomograms in contemporary clinical practice.

Intracompartmental pressure as a predictor of intratesticular blood flow: a rat model.

PURPOSE: We identified an intratesticular pressure at which vascular flow would cease in a testicular compartment syndrome model, defining a critical vascular stop flow pressure. MATERIALS AND METHODS: A total of 52 male Sprague Dawley® rats were used for the study. The testicle of each rat was delivered from the scrotum and size measurements were taken. An intracompartment pressure monitor needle was inserted into the testis to record basal intratesticular pressure. The monitor needle remained in the testicle for the duration of the procedure. Vascular flow within the testis was measured using a variable frequency linear ultrasound transducer with color flow and pulse wave Doppler modalities. Saline was infused through the compartment monitor in 5 mm Hg increments via a pressure infusion pump. Following each 5 mm Hg increase intratesticular vascular blood flow and velocities were recorded using color flow and pulse wave, respectively. Data collection proceeded until color flow images indicated a complete absence of flow within the testis. RESULTS: Using a paired t-test (p <0.0001), mean color flow stop flow pressure was 52.17 mm Hg (95% CI 49.57-54.77) and pulse wave stop flow pressure was 36.34 mm Hg (95% CI 33.90-38.77). Regression analysis of pulse wave vs color flow showed a slope of 0.6960 ± 0.09112, a y-intercept of 0.02427 ± 4.824 and an x-intercept of -0.03486. CONCLUSIONS: This is the first known study to characterize a stop flow pressure within the testicular parenchyma resulting from an increased intracompartmental pressure. Due to probe sensitivity limitations, color flow appears to provide the most precise mean pressure of occlusion of 52.17 mm Hg.