A Randomized Trial Evaluating the Use of a Smart Water Bottle to Increase Fluid Intake in Stone Formers.

OBJECTIVE: The aim of this study is to evaluate if the use of a smart water bottle improves urine volume in stone forming patients. METHODS: Adults with nephrolithiasis and low urine volume (<1.5 L) documented on a 24-hour urinalysis (24 hr U) were randomized to receive either standard dietary recommendations to increase fluid intake (DR arm), or DR and a smart water bottle (HidrateSpark®; Hydrate Inc., Minneapolis, MN) that recorded fluid intake, synced to the user's smartphone, and provided reminders to drink (SB arm). Participants completed baseline surveys assessing barriers to hydration. They then repeated a 24 hr U and survey at 6 and 12 weeks, respectively. RESULTS: Eighty-five subjects (44 DR, 41 SB) were enrolled. The main baseline factor limiting fluid intake was not remembering to drink (60%). Follow-up 24 hr Us were available for 51 patients. The mean increase in volume was greater in the SB arm (1.37 L, 95% confidence interval -0.51 to 3.25) than the DR arm (0.79 L, 95% confidence interval -1.15 to 2.73) (P = .04). A smaller percentage of subjects in the SB arm reported not remembering to drink as the main factor limiting fluid intake in the follow-up questionnaire compared to baseline (45.4% vs. 68.4%, P < .05). This was not true for the DR arm (40.0% vs. 51.2%, P = .13). CONCLUSIONS: Difficulty remembering to drink is a barrier to achieving sufficient fluid intake in stone formers. The use of a smart bottle was associated with greater increases in 24 hr U volumes and less difficulty remembering to drink.

Neoadjuvant letrozole plus taselisib versus letrozole plus placebo in postmenopausal women with oestrogen receptor-positive, HER2-negative, early-stage breast cancer (LORELEI): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Endocrine therapy-based neoadjuvant treatment for luminal breast cancer allows efficient testing of new combinations before surgery. The activation of the phosphatidylinositol-3-kinase (PI3K) pathway is a known mechanism of resistance to endocrine therapy. Taselisib is an oral, selective PI3K inhibitor with enhanced activity against PIK3CA-mutant cancer cells. The LORELEI trial tested whether taselisib in combination with letrozole would result in an increased proportion of objective responses and pathological complete responses. METHODS: In this multicentre, randomised, double-blind, parallel-cohort, placebo-controlled phase 2, study, we enrolled postmenopausal women (aged ≥18 years) with histologically confirmed, oestrogen receptor (ER)-positive, HER2-negative, stage I-III, operable breast cancer, from 85 hospitals in 22 countries worldwide. To be eligible, patients had have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate organ function, and had to have evaluable tumour tissue for PIK3CA genotyping. Patients were randomly assigned (1:1) by means of a permuted block algorithm (block size of four) via an interactive voice or web-based response system, to receive letrozole (2·5 mg/day orally, continuously) with either 4 mg of oral taselisib or placebo (on a 5 days-on, 2 days-off schedule) for 16 weeks, followed by surgery. Randomisation was stratified by tumour size and nodal status. Site staff, patients, and the sponsor were masked to treatment assignment. Coprimary endpoints were the proportion of patients who achieved an objective response by centrally assessed breast MRI and a locally assessed pathological complete response in the breast and axilla (ypT0/Tis, ypN0) at surgery in all randomly assigned patients and in patients with PIK3CA-mutant tumours. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02273973, and is closed to accrual. FINDINGS: Between Nov 12, 2014, and Aug 12, 2016, 334 participants were enrolled and randomly assigned to receive letrozole and placebo (n=168) or letrozole and taselisib (n=166). Median follow-up was 4·9 months (IQR 4·7-5·1). The study met one of its primary endpoints: the addition of taselisib to letrozole was associated with a higher proportion of patients achieving an objective response in all randomly assigned patients (66 [39%] of 168 patients in the placebo group vs 83 [50%] of 166 in the taselisib group; odds ratio [OR] 1·55, 95% CI 1·00-2·38; p=0·049) and in the PIK3CA-mutant subset (30 [38%] of 79 vs 41 [56%] of 73; OR 2·03, 95% CI 1·06-3·88; p=0·033). No significant differences were observed in pathological complete response between the two groups, either in the overall population (three [2%] of 166 in the taselisib group vs one [1%] of 168 in the placebo group; OR 3·07 [95% CI 0·32-29·85], p=0·37) or in the PIK3CA-mutant cohort (one patient [1%) vs none [0%]; OR not estimable, p=0·48). The most common grade 3-4 adverse events in the taselisib group were gastrointestinal (13 [8%] of 167 patients), infections (eight [5%]), and skin-subcutaneous tissue disorders (eight [5%]). In the placebo group, four (2%) of 167 patients had grade 3 or worse vascular disorders, two (1%) had gastrointestinal disorders, and two (1%) patients had grade 3 or worse infections and infestations. There was no grade 4 hyperglycaemia and grade 3 cases were asymptomatic. Serious adverse events were more common in the taselisib group (eight [5%] patients with infections and seven [4%] with gastrointestinal effects) than in the placebo group (one [1%] patient each with grade 3 postoperative wound and haematoma infection, grade 4 hypertensive encephalopathy, grade 3 acute cardiac failure, and grade 3 breast pain). One death occurred in the taselisib group, which was not considered to be treatment-related. INTERPRETATION: The increase in the proportion of patients who achieved an objective response from the addition of taselisib to endocrine therapy in a neoadjuvant setting is consistent with the clinical benefit observed in hormone receptor-positive, HER2-negative, metastatic breast cancer. FUNDING: Genentech and F Hoffmann-La Roche.

Liver X receptor (LXR) partial agonists: biaryl pyrazoles and imidazoles displaying a preference for LXRß.

A series of biaryl pyrazole and imidazole Liver X Receptor (LXR) partial agonists has been synthesized displaying LXRß selectivity. The LXRß selective partial agonist 18 was identified with potent induction of ATP binding transporters ABCA1 and ABCG1 in human whole blood (EC50=1.2µM, 55% efficacy). In mice 18 displayed peripheral induction of ABCA1 at 3 and 10mpk doses with no significant elevation of plasma or hepatic triglycerides at these doses, showing an improved profile compared to a full pan-agonist.

Robotic Partial vs Radical Nephrectomy for Clinical T3a Tumors: A Narrative Review.

Introduction: T3a renal masses include a diverse group of tumors that invade the perirenal and/or sinus fat, pelvicaliceal system, or renal vein. The majority of cT3a renal masses represent renal cell carcinoma (RCC) and have historically been treated with radical nephrectomy (RN) given their aggressive nature. With the adoption of minimally invasive approaches to renal surgery, the combination of improved observation, pneumoperitoneum, and robotic articulation has allowed urologists to consider partial nephrectomy (PN) for more complex tumors. Herein, we review the existing literature regarding robot-assisted PN (RAPN) and robot-assisted RN (RARN) in the management of T3a renal masses. Methods: A literature search was performed using PubMed for articles evaluating the role of RARN and RAPN for T3a renal masses. Search parameters were limited to English language studies. Applicable studies were abstracted and included in this narrative review. Results: T3a RCC caused by renal sinus fat or venous involvement is associated with ∼50% lower cancer-specific survival than those with perinephric fat invasion alone. CT and MRI can both be used to stage cT3a tumors, however, MRI is more accurate when assessing venous involvement. Upstaging to pT3a RCC during RAPN does not confer a worse prognosis than pT3a tumors treated with RARN; however, patients who undergo RAPN for T3a RCC with venous involvement have relatively higher rates of recurrence and metastasis. Intraoperative tools including drop-in ultrasound, near-infrared fluorescence, and 3D virtual models improve the ability to perform RAPN for T3a tumors. In well-selected cases, warm ischemia times remain reasonable. Conclusions: cT3a renal masses represent a diverse group of tumors. Depending on substratification of cT3a, RARN or RAPN can be employed for treatment of such masses.

Immediate gemcitabine bladder instillation following bladder closure during robotic-assisted radical nephroureterectomy: a multi-institutional report of feasibility and initial outcomes.

Background: Bladder recurrence after radical nephroureterectomy (RNU) is common and randomized data supports utilization of prophylactic intravesical mitomycin to reduce recurrence. Recently, gemcitabine has been shown to be safe and effective at reducing recurrence following transurethral resection of bladder tumors. We sought to evaluate the safety and efficacy of a single, intraoperative gemcitabine instillation immediately following bladder cuff closure during RNU, and to compare outcomes with non-gemcitabine intravesical chemotherapy agents. Methods: We retrospectively reviewed all patients from two high volume centers who underwent robotic-assisted RNU between 2016-2020 and received either 2 g intravesical gemcitabine immediately following bladder cuff closure or non-gemcitabine intravesical chemotherapies [40 mg mitomycin C (MMC) or 50 mg doxorubicin] at the beginning of the procedure. Clinicopathologic factors were compared between cohorts. Bladder recurrence rates were evaluated using the Kaplan-Meier method and log-rank test. Results: During RNU, 24 patients received gemcitabine and 31 patients received non-gemcitabine chemotherapy. In total, 35% (19/55) of patients experienced a bladder cancer recurrence. There was no significant difference in estimated bladder recurrence-free survival (bRFS) between gemcitabine and non-gemcitabine patient cohorts (P=0.64). By 12 months post-surgery, 25% of patients had experienced bladder recurrence. The estimated 1-year bladder RFS survival was 73% for gemcitabine and 76% for non-gemcitabine chemotherapy. Overall survival and cancer-specific survival did not differ between cohorts. No adverse events potentially attributable to the use of gemcitabine were noted within 30 days postoperatively. Conclusions: Gemcitabine instilled immediately following bladder cuff closure during RNU has similar bRFS rates compared to established chemotherapy agents instilled at the start of surgery.

Multi-institutional feasibility and safety outcomes of retroperitoneal robot-assisted partial nephrectomy in morbidly obese patients.

Background: Robotic-assisted partial nephrectomy (RAPN) is an established treatment modality for small renal masses. While retroperitoneal RAPN (rRAPN) has the benefit of avoiding the peritoneal cavity and provides more direct access to the renal hilum and posterior kidney, there is concern about the feasibility of rRAPN particularly in morbidly obese [body mass index (BMI) ≥40 kg/m2] patients. We present a large scale multi-institutional study on the outcomes of rRAPN in morbidly obese patients. Methods: A retrospective review of a cohort of morbidly obese patients who underwent rRAPN at two academic institutions was performed. Patient characteristics, operative data, and postoperative complication rates were assessed. Results: A total of 22 morbidly obese patients were included for analysis, with a median follow-up duration of 52 months. Median patient age was 61 years and median BMI was 44.9 kg/m2. Based on nephrometry score, 55% of the masses had low complexity and 32% had intermediate complexity. Median operative time was 186.0 minutes and median warm ischemia time was 23.5 minutes. Median postoperative length of stay was 2 days, and only one patient experienced a high-grade complication within 30 days of surgery. Conclusions: rRAPN in select morbidly obese patients appears to have acceptable operative and postoperative outcomes. Further studies and follow-up are needed to better generalization and understand long-term impacts.

Technique and outcomes of robotic-assisted retroperitoneal radical nephrectomy.

Background: Robotic retroperitoneal partial nephrectomy (rRPN) has numerous advantages over transperitoneal surgery, including direct access to the renal hilum and posterior tumors, and avoidance of the peritoneal cavity in patients with a hostile abdomen. Although the use of the retroperitoneal approach has increased over the last decade, there is little literature on robotic retroperitoneal radical nephrectomy (rRRN), which has similar benefits over the transperitoneal approach. The aim of this study was to describe our technique for robotic retroperitoneal nephrectomy (rRN) and assess its feasibility and outcomes at a high-volume center. Methods: A retrospective review of patients who underwent some form of rRN [rRRN, robotic retroperitoneal simple nephrectomy (rRSN), or robotic retroperitoneal nephroureterectomy (rRNU)] at a single institution between 2013 and 2023. Patient characteristics, operative data, and postoperative complication rates were assessed. The technique for rRN was detailed. Results: A total of 13 renal units in 12 patients were included for analysis (7 rRRN, 5 rRSN, 1 rRNU). Median patient age was 64.0 years, and median body mass index (BMI) was 36.0 kg/m2. Indications for retroperitoneal surgery were prior abdominal surgery in all patients, including three with bowel diversions, super morbid central obesity in two patients, and a large ventral hernia in one patient. Median operative time was 213 minutes and median estimated blood loss (EBL) was 85 cc. Median postoperative length of stay (LOS) was 3 days, and only one patient experienced a Clavien-Dindo grade ≥3 complication within 90 days of surgery. Conclusions: The retroperitoneal approach for robotic-assisted nephrectomy is feasible and associated with similar outcomes as the transperitoneal approach. This approach may prove beneficial in select patients with significant prior abdominal surgery including those who are morbidly obese.

Multiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2-, PIK3CA-mutated breast cancers.

BACKGROUND: Mutations in the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), encoded by the PIK3CA gene, cause dysregulation of the PI3K pathway in 35-40% of patients with HR+/HER2- breast cancer. Preclinically, cancer cells harboring double or multiple PIK3CA mutations (mut) elicit hyperactivation of the PI3K pathway leading to enhanced sensitivity to p110α inhibitors. METHODS: To understand the role of multiple PIK3CAmut in predicting response to p110α inhibition, we estimated the clonality of multiple PIK3CAmut in circulating tumor DNA (ctDNA) from patients with HR+/HER2- metastatic breast cancer enrolled to a prospectively registered clinical trial of fulvestrant ± taselisib, and analyzed the subgroups against co-altered genes, pathways, and outcomes. RESULTS: ctDNA samples with clonal multiple PIK3CAmut had fewer co-alterations in receptor tyrosine kinase (RTK) or non-PIK3CA PI3K pathway genes compared to samples with subclonal multiple PIK3CAmut indicating a strong reliance on the PI3K pathway. This was validated in an independent cohort of breast cancer tumor specimens that underwent comprehensive genomic profiling. Furthermore, patients whose ctDNA harbored clonal multiple PIK3CAmut exhibited a significantly higher response rate and longer progression-free survival vs subclonal multiple PIK3CAmut. CONCLUSIONS: Our study establishes clonal multiple PIK3CAmut as an important molecular determinant of response to p110α inhibition and provides rationale for further clinical investigation of p110α inhibitors alone or with rationally-selected therapies in breast cancer and potentially other solid tumor types.

ER+, HER2- advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes.

Taselisib is a potent ß-sparing phosphatidylinositol 3-kinase (PI3K) inhibitor that, with endocrine therapy, improves outcomes in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated (PIK3CAmut) advanced breast cancer. To understand alterations associated with response to PI3K inhibition, we analysed circulating tumour DNA (ctDNA) from participants enrolled in the SANDPIPER trial. Participants were designated as either PIK3CAmut or PIK3CA no mutation was detected (NMD) per baseline ctDNA. The top mutated genes and tumour fraction estimates identified were analysed for their association with outcomes. In participants with PIK3CAmut ctDNA treated with taselisib + fulvestrant, tumour protein p53 (TP53; encoding p53) and fibroblast growth factor receptor 1 (FGFR1) alterations were associated with shorter progression-free survival (PFS) compared to participants with NMD in these genes. Conversely, participants with PIK3CAmut ctDNA harbouring a neurofibromin 1 (NF1) alteration or high baseline tumour fraction estimate experienced improved PFS upon treatment with taselisib + fulvestrant compared to placebo + fulvestrant. Broadly, alterations in oestrogen receptor (ER), PI3K and p53 pathway genes were associated with resistance to taselisib + fulvestrant in participants with PIK3CAmut ctDNA. Altogether, we demonstrated the impact of genomic (co-)alterations on outcomes with one of the largest clinico-genomic datasets of ER+, HER2-, PIK3CAmut breast cancer patients treated with a PI3K inhibitor.

The design, synthesis, and biological evaluation of PIM kinase inhibitors.

A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure.

The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors.

Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models.

Discovery of XL413, a potent and selective CDC7 inhibitor.

CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model.

SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors.

We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives as potent and selective JAK2 inhibitors. High throughput screening of our in-house compound library led to the identification of hit 1, from which optimization resulted in the discovery of highly potent and selective JAK2 inhibitors. Advanced lead 10d demonstrated a significant dose-dependent pharmacodynamic and antitumor effect in a mouse xenograft model. Based upon the desirable profile of 10d (XL019) it was advanced into clinical trials.

Growth-rate model predicts in vivo tumor response from in vitro data.

A major challenge in oncology drug development is to elucidate why drugs that show promising results in cancer cell lines in vitro fail in mouse studies or human trials. One of the fundamental steps toward solving this problem is to better predict how in vitro potency translates into in vivo efficacy. A common approach to infer whether a model will respond in vivo is based on in vitro half-maximal inhibitory concentration values (IC50 ), but yields limited quantitative comparison between cell lines and drugs, potentially because cell division and death rates differ between cell lines and in vivo models. Other methods based either on mechanistic modeling or machine learning require molecular insights or extensive training data, limiting their use for early drug development. To address these challenges, we propose a mathematical model integrating in vitro growth rate inhibition values with pharmacokinetic parameters to estimate in vivo drug response. Upon calibration with a drug-specific factor, our model yields precise estimates of tumor growth rate inhibition for in vivo studies based on in vitro data. We then demonstrate how our model can be used to study dosing schedules and perform sensitivity analyses. In addition, it provides meaningful metrics to assess association with genotypes and guide clinical trial design. By relying on commonly collected data, our approach shows great promise for optimizing drug development, better characterizing the efficacy of novel molecules targeting proliferation, and identifying more robust biomarkers of sensitivity while limiting the number of in vivo experiments.

Clinical Utility of Rigid Blue Light Cystoscopy: Results from a Post Procedure User Survey in a Prospective Multicenter Registry.

INTRODUCTION: Despite the effectiveness of blue light cystoscopy (BLC) in the management of bladder cancer, the adoption of BLC since its approval has been limited. We evaluated the perceived clinical utility of BLC and assessed factors associated with higher perceived utility of BLC. METHODS: This study used a prospective multi-institutional registry of patients with known or suspected noninvasive bladder cancer. Following BLC, urologists assessed their perceived clinical utility of BLC on a 4-point Likert scale. The primary outcome was the perceived clinical utility of BLC as assessed by participating urologists. RESULTS: A total of 1,702 rigid cystoscopies performed between 2014 and 2019 were evaluated. Of all lesions biopsied 2,285 were identified with both white light and blue light (60.6%), followed by 867 with blue light only (23.0%) and 423 with white light only (11.2%). Among all post-cystoscopy surveys, urologists perceived BLC to be of some utility (38.1%, 648), moderate assistance (25.4%, 432), essential (19%, 324) and no real utility (17.5%, 298). More urologists perceived BLC to be essential in 2019 (28.3%, 30/106) compared to in 2014 (11.5%, 9/78; p=0.006). On multivariable analysis higher perceived utility was associated with more lesions seen only with blue light (LR 4.88, CI 2.27-8.78), malignant pathology on biopsy (LR 3.31, CI 2.10-5.23), and total number of lesions seen with blue light (LR 1.36, CI 1.19-1.55). CONCLUSIONS: The perceived clinical utility of BLC has been increasing over time, particularly among high-volume urologists. Urologists who identify more lesions with BLC than white light cystoscopy perceive BLC to be most clinically useful.

Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations.

PURPOSE: Understanding the differences in biomarker prevalence that may exist among diverse populations is invaluable to accurately forecast biomarker-driven clinical trial enrollment metrics and to advance inclusive research and health equity. This study evaluated the frequency and types of PIK3CA mutations (PIK3CAmut) detected in predicted genetic ancestry subgroups across breast cancer (BC) subtypes. METHODS: Analyses were conducted using real-world genomic data from adult patients with BC treated in an academic or community setting in the United States and whose tumor tissue was submitted for comprehensive genomic profiling. RESULTS: Of 36,151 patients with BC (median age, 58 years; 99% female), the breakdown by predicted genetic ancestry was 75% European, 14% African, 6% Central/South American, 3% East Asian, and 1% South Asian. We demonstrated that patients of African ancestry are less likely to have tumors that harbor PIK3CAmut compared with patients of European ancestry with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) BC (37% [949/2,593] v 44% [7,706/17,637]; q = 4.39E-11) and triple-negative breast cancer (8% [179/2,199] v 14% [991/7,072]; q = 6.07E-13). Moreover, we found that PIK3CAmut were predominantly composed of hotspot mutations, of which mutations at H1047 were the most prevalent across BC subtypes (35%-41% ER+/HER2- BC; 43%-61% HER2+ BC; 40%-59% triple-negative breast cancer). CONCLUSION: This analysis established that tumor PIK3CAmut prevalence can differ among predicted genetic ancestries across BC subtypes on the basis of the largest comprehensive genomic profiling data set of patients with cancer treated in the United States. This study highlights the need for equitable representation in research studies, which is imperative to ensuring better health outcomes for all.

A Visual Scale for Improving Communication When Describing Gross Hematuria.

OBJECTIVE: To create and validate a grading scale that facilitates communication between providers managing gross hematuria (GH). METHODS: A blood simulant was used to create a spectrum of GH in 5 foley catheter tubes which were shown to a group of experienced urologists. The urologists were asked how they would adjust the continuous bladder irrigation rate if the samples represented the urine of hypothetical patients, and a 5-point scale was created by group consensus with pictures of the representative tubes printed onto a visual aid. Another cohort were then shown the 5 tubes at random and asked to describe the GH. Raters were then shown the visual aid and asked to assign a grade to the same samples. Fleiss' kappa analysis was used to measure inter-rater agreement, and therefore fidelity of the scale. RESULTS: Fourteen urologists were surveyed to determine the samples used to create the 5-point scale. After the scale was created, 43 raters (22 nurses, 16 urologists, and 5 advanced practice providers) attempted match the tubes to their corresponding images on the printout. When asked to describe the degree of GH for the samples as they would in clinical practice, 28 different descriptors were used (mean 8.6 per sample). When using the 5-point GH scale, however, raters exhibited near perfect agreement in matching each sample to its corresponding severity on the scale (κ = 0.93, P < .001). CONCLUSION: We created a clinically useful GH scale that improves communication and reduces ambiguous language among providers of varying levels of experience.

A Laparoscopic Approach to Parastomal Hernia Repair With Re-Siting of Urinary Stoma.

BACKGROUND: Parastomal and ventral hernias are common complications in patients with continent catheterizable channels or incontinent urinary diversions. Patients with neurogenic bladder are at particularly high risk due to weak abdominal wall musculature, and hernia repair often requires resiting of their stoma. While parastomal hernia repair with urinary stoma resiting has acceptable long-term success rates, it often necessitates a laparotomy which is associated with significant morbidity. OBJECTIVE: To describe a novel approach to combined laparoscopic parastomal hernia repair with resiting of the urinary stoma in patients with neurogenic bladder. The video will outline the surgical steps and pitfalls. MATERIALS AND METHODS: The case begins laparoscopically or robotically with adhesiolysis to dissect out the subfascial portion of the channel and the parastomal hernia. The subfascial portion of the channel is dissected out to the anterior abdominal wall, ensuring to preserve its mesentery. The abdomen is then desufflated and the suprafascial portion of the channel is dissected and the channel dropped into the abdomen. The hernia is then repaired laparoscopically using mesh and the channel is brought out through one of the laparoscopic port sites and matured to the skin. RESULTS: In our series of 4 patients, this technique was performed for 2 continent catheterizable channels and 2 incontinent diversions. One patient developed a hernia recurrence 7 months later which was repaired laparoscopically. In another, the stoma was successfully resited but the hernia was unable to be repaired laparoscopically due to dense adhesions. Continent and patency outcomes of the urinary stomas were 100% at a mean follow-up of 2 years. CONCLUSION: Laparoscopic parastomal hernia repair with resiting of the urinary stoma has similar long-term success rates compared to that of an open repair and avoids the morbidity of a laparotomy. This repair can be performed for catheterizable channels or incontinent diversions.

MRI/PET Imaging in elevated PSA and localized prostate cancer: a narrative review.

OBJECTIVE: To review the recent milestones in MRI and PET based imaging and evaluate their evolving role in the setting of elevated PSA as well as localized prostate cancer. BACKGROUND: The importance of multiparametric MRI (mpMRI) and PET based imaging for the diagnosis and staging of prostate cancer cannot be understated. Accurate staging has become another significant milestone with the use of PET scans, particularly with prostate specific radiotracers like 68-Gallium Prostate Specific Membrane Antigen (68Ga-PSMA). Integrated PET/MRI systems are commercially available and can be modulated to evaluate the unique needs of localized as well as recurrent prostate cancer. METHODS: A literature search was performed using PubMed and Google Scholar using the MeSH compliant and other keywords that included prostate cancer, PSA, mpMRI, PET CT, PET/MRI. CONCLUSIONS: mpMRI has now established itself as the gold-standard of local prostate imaging and has been incorporated into international guidelines as part of the diagnostic work-up of prostate cancer. PSMA PET/CT has shown superiority over conventional imaging even in staging of localized prostate cancer based on recent randomized control data. Imaging parameters from PET/MRI have been shown to be associated with malignancy, Gleason score and tumour volume. As mpMRI and PSMA PET/CT become more ubiquitous and established; we can anticipate more high-quality data, cost optimization and increasing availability of PET/MRI to be ready for primetime in localized prostate cancer.

Evaluating the Perceived Importance of Male Ejaculatory Function.

OBJECTIVE: To assess the perceived importance of male ejaculatory function (EjF) from the perspective of adult men and their sexual partners. METHODS: In a large survey study, men were asked about the importance of their own EjF. Sexual partners of men were asked about the general importance their partner's EjF, and whether they would support a partner's decision to pursue BPH treatment despite ejaculatory dysfunction. RESULTS: One hundred and two men completed the survey section regarding their own EjF, and 100 participants completed the survey section assessing the importance of their male partner's EjF. While 55% of men agreed or strongly agreed that "ejaculation is an important part of an enjoyable sexual experience," only 30% of partners similarly agreed or strongly agreed (P = .005). A greater percentage of men (12%) agreed or strongly agreed that they "preferred large semen volume" compared to sexual partners of men (3%), however this was not significant. Sixty eight percent of sexual partners would agree or strongly agree to support their male partner's decision to pursue BPH treatment despite potential ejaculatory dysfunction. CONCLUSION: The perceived importance of EjF differs between men and their sexual partners, as men believe ejaculation to be a more important component of an enjoyable sexual experience than their partners.