Pathological and Clinical Outcomes in a Large Surveillance and Intervention Cohort of Radiographically Cystic Renal Masses.

PURPOSE: We evaluated oncologic risks in a large cohort of patients with radiographic cystic renal masses who underwent active surveillance or intervention. MATERIALS AND METHODS: A single-institutional database of 4,340 kidney lesions managed with either active surveillance or intervention between 2000-2020 was queried for radiographically cystic renal masses. Association of radiographic tumor characteristics and high-grade pathology was evaluated. RESULTS: We identified 387 radiographically confirmed cystic lesions in 367 patients. Of these, 247 were resected (n=240) or ablated (n=7; n=247, 203 immediate vs 44 delayed intervention). Pathologically, 23% (n=56) demonstrated high-grade pathology. Cystic features were explicitly described by pathology in only 18% (n=33) of all lesions and in 7% (n=4) of high-grade lesions. Of the intervention cohort, African American race, male gender, and Bosniak score were associated with high-grade pathology (P < .05). On active surveillance (n=184), Bosniak IV lesions demonstrated faster growth rates than IIF and III lesions (2.7 vs 0.6 and 0.5 mm/y, P ≤ .001); however, growth rates were not associated with high-grade pathology (P = .5). No difference in cancer-specific survival was identified when comparing intervention vs active surveillance at 5 years (99% vs 100%, P = .2). No difference in recurrence was observed between immediate intervention vs delayed intervention (P > .9). CONCLUSIONS: A disconnect between "cystic" designation on imaging and pathology exists for renal lesions. Over 80% of radiographic Bosniak cystic lesions are not described as "cystic" on pathology reports. More than 1 in 5 resected cystic renal lesions demonstrated high-grade disease. Despite this finding, judiciously managed active surveillance ± delayed intervention is a safe and effective management option for most radiographic cystic renal masses.

Dysgenesis of enteroendocrine cells in Aristaless-Related Homeobox polyalanine expansion mutations.

OBJECTIVES: Severe congenital diarrhea occurs in approximately half of patients with Aristaless-Related Homeobox (ARX) null mutations. The cause of this diarrhea is unknown. In a mouse model of intestinal Arx deficiency, the prevalence of a subset of enteroendocrine cells is altered, leading to diarrhea. Because polyalanine expansions within the ARX protein are the most common mutations found in ARX-related disorders, we sought to characterize the enteroendocrine population in human tissue of an ARX mutation and in a mouse model of the corresponding polyalanine expansion (Arx). METHODS: Immunohistochemistry and quantitative real-time polymerase chain reaction were the primary modalities used to characterize the enteroendocrine populations. Daily weights were determined for the growth curves, and Oil-Red-O staining on stool and tissue identified neutral fats. RESULTS: An expansion of 7 alanines in the first polyalanine tract of both human ARX and mouse Arx altered enteroendocrine differentiation. In human tissue, cholecystokinin, glucagon-like peptide 1, and somatostatin populations were reduced, whereas the chromogranin A population was unchanged. In the mouse model, cholecystokinin and glucagon-like peptide 1 populations were also lost, although the somatostatin-expressing population was increased. The ARX protein was present in human tissue, whereas the Arx protein was degraded in the mouse intestine. CONCLUSIONS: ARX/Arx is required for the specification of a subset of enteroendocrine cells in both humans and mice. Owing to protein degradation, the Arx mouse recapitulates findings of the intestinal Arx null model, but is not able to further the study of the differential effects of the ARX protein on its transcriptional targets in the intestine.

Impaired enteroendocrine development in intestinal-specific Islet1 mouse mutants causes impaired glucose homeostasis.

Enteroendocrine cells secrete over a dozen different hormones responsible for coordinating digestion, absorption, metabolism, and gut motility. Loss of enteroendocrine cells is a known cause of severe congenital diarrhea. Furthermore, enteroendocrine cells regulate glucose metabolism, with the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) playing critical roles in stimulating insulin release by pancreatic ß-cells. Islet1 (Isl1) is a LIM-homeodomain transcription factor expressed specifically in an array of intestinal endocrine cells, including incretin-expressing cells. To examine the impact of intestinal Isl1 on glycemic control, we set out to explore the role of intestinal Isl1 in hormone cell specification and organismal physiology. Mice with intestinal epithelial-specific ablation of Isl1 were obtained by crossing Villin-Cre transgenic animals with mice harboring a Isl1(loxP) allele (Isl1(int) model). Gene ablation of Isl1 in the intestine results in loss of GLP-1, GIP, cholecystokinin (CCK), and somatostatin-expressing cells and an increase in 5-HT (serotonin)-producing cells, while the chromogranin A population was unchanged. This dramatic change in hormonal milieu results in animals with lipid malabsorption and females smaller than their littermate controls. Interestingly, when challenged with oral, not intraperitoneal glucose, the Isl-1 intestinal-deficient animals (Isl1(int)) display impaired glucose tolerance, indicating loss of the incretin effect. Thus the Isl1(int) model confirms that intestinal biology is essential for organism physiology in glycemic control and susceptibility to diabetes.

Transition to Value-based Healthcare: Development, Implementation, and Results of an Optimal Surgical Care Framework at a National Cancer Institute-designated Comprehensive Cancer Center.

BACKGROUND: The continued rise in healthcare expenditures has not produced commensurate improvements in patient outcomes, leading US healthcare stakeholders to emphasize value-based care. Transition to such a model requires all team members to adopt a new strategic and organizational framework. OBJECTIVE: To describe and report a strategy for the implementation of a novel patient-centered value-based "optimal surgical care" (OSC) framework, with validation and cost analysis in kidney surgery. DESIGN, SETTING, AND PARTICIPANTS: An observational study of care episodes at a single institution from 2014 to 2019 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multidisciplinary teams defined OSC by core and procedure-specific metrics using a combination of provider-based ("bottom-up") and "clinical leadership"-based ("top-down") strategies. Baseline OSC rates across were established, while identifying proportions of OSC achieved by coefficient of variation (CV) in total direct costs. Multivariable linear regression comparing cost between OSC and non-OSC encounters was performed, adjusting for patient characteristics. RESULTS AND LIMITATIONS: An analysis of 30 261 perioperative care episodes was performed. Following the implementation of an OSC framework, there was an increase in OSC rates across all procedure buckets using core (25%) and procedure-specific (26%) metrics. Among the tumors tested, kidney cancer surgical episodes held the highest OSC rate improvement (67%) with lowest variability in cost (CV 0.5). OSC was associated with significant total cost savings across all tumor types after adjusting for inflation (p < 0.05). Compared with non-OSC episodes, a significant reduction in the cost ratio of OSC was noted for renal surgery (p < 0.01), with estimated costs savings of $2445.87 per OSC encounter. CONCLUSIONS: Institutional change directing efforts toward optimizing surgical care and emphasizing value rather than focusing solely on expense reduction is associated with improved outcomes, while potentially reducing costs. The strategy for implementation requires serial performance analyses, engaging and educating providers, and continuous ongoing adjustments to achieve durable results. PATIENT SUMMARY: In this study, we report our strategy and outcomes for transitioning to a value-based healthcare model using a novel "optimal surgical care" framework at a National Cancer Institute-designated comprehensive cancer center. We observed an increase in optimal surgical care episodes across all specialties after 5 yr, with a potential associated reduction in cost expenditure. We conclude that the key to a successful and sustained transition is the implementation strategy, focusing on continual review and provider engagement.

Robot-Assisted Laparoscopic Distal Ureteroureterostomy for Distal Benign Ureteral Strictures with Long-Term Follow-Up.

Objectives: To demonstrate feasibility of robot-assisted laparoscopic (RAL) ureteroureterostomy (UU) for benign distal ureteral strictures (DUS) in our robotic reconstruction series with long-term follow-up. Patients and Methods: In a retrospective review of our prospectively maintained RAL ureteral reconstruction database, we followed patients between June 2012 and February 2019 who underwent a UU for DUS. In addition to patient demographics, we recorded the etiology, stricture length, and recurrence rates. Recurrence was defined as findings of recurrent or persistent obstruction by postoperative mercaptoacetyltriglycine diuretic renal scan or the need for additional intervention with ureteral drainage or revisional surgery. Results: We identified 22 patients who underwent a RAL-UU for DUS of benign etiologies. Median age was 42 years (interquartile range [IQR] 39-57) and 20 of 22 patients (90.1%) were women. Median stricture length was 1.5 cm (IQR 1-2). Iatrogenic surgical injury was noted in 16 patients (73%). All ureteral reconstruction was performed using RAL. Postoperative imaging consisted of renal ultrasonography, diuretic renal scan, or cross-sectional radiology within 3 months of the index operation. Further imaging was dependent on clinical judgment. Twenty patients (90.1%) had success with median follow-up time of 54.6 months with two recurrences necessitating RAL ureteroneocystostomy (UNC). Conclusion: RAL-UU for DUS is technically viable and shows promising efficacy in properly selected patients. This technique may serve a niche for preserving the natural anatomical drainage of the bladder and ureter in addition to obviating the sequela of vesicoureteral reflux as seen in UNC.

Perioperative and Functional Outcomes of Robot-assisted Ureteroenteric Reimplantation: A Multicenter Study of Seven Referral Institutions.

BACKGROUND: Open revision of ureteroenteric strictures (UESs) is associated with considerable morbidity. There is a lack of data evaluating the feasibility of robotic revisions. OBJECTIVE: To analyze the perioperative and functional outcomes of robot-assisted ureteroenteric reimplantation (RUER) for the management of UESs after radical cystectomy (RC). DESIGN SETTING AND PARTICIPANTS: A retrospective multicenter study of 61 patients, who underwent 63 RUERs at seven high-volume institutions between 2009 and 2020 for benign UESs after RC, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were reviewed for demographics, stricture characteristics, and perioperative outcomes. Variables associated with being stricture free after an RUER were evaluated using a multivariate Cox regression analysis. RESULTS AND LIMITATIONS: Among 63 RUERs, 22 were right sided (35%), 34 left sided (54%), and seven bilateral (11%). Twenty-seven (44%) had prior abdominal/pelvic surgery and five (8%) radiotherapy (RT). Thirty-two patients had American Society of Anesthesiologists (ASA) scores I-II (52%) and 29 ASA III (48%). Forty-two (68%) RUERs were in ileal conduits, 18 (29%) in neobladders, and two (3%) in Indiana pouch. The median time to diagnosis of a UES from cystectomy was 5 (3-11) mo. Of the UESs, 28 (44%) failed an endourological attempt (balloon dilatation/endoureterotomy). The median RUER operative time was 195 (175-269) min. No intraoperative complications or conversions to open approach were reported. Twenty-three (37%) patients had postoperative complications (20 [32%] were minor and three [5%] major). The median length of hospital stay was 3 (1-6) d and readmissions were 5%. After a median follow-up of 19 (8-43) mo, 84% of cases were stricture free. Lack of prior RT was the only variable associated with better stricture-free survival after RUER (hazard ratio 6.8, 95% confidence interval 1.10-42.00, p = 0.037). The study limitations include its retrospective nature and the small number of patients. CONCLUSIONS: RUER is a feasible procedure for the management of UESs. Prospective and larger studies are warranted to prove the safety and efficacy of this technique. PATIENT SUMMARY: In this study, we investigate the feasibility of a novel minimally invasive technique for the management of ureteroenteric strictures. We conclude that robotic reimplantation is a feasible and effective procedure.

Robotic Ureteral Reconstruction in Patients with Radiation-Induced Ureteral Strictures: Experience from the Collaborative of Reconstructive Robotic Ureteral Surgery.

Objectives: Management of radiation-induced ureteral stricture (RIUS) is complex, requiring chronic drainage or morbid definitive open reconstruction. Herein, we report our multi-institutional comprehensive experience with robotic ureteral reconstruction (RUR) in patients with RIUSs. Patients and Methods: In a retrospective review of our multi-institutional RUR database between January 2013 and January 2020, we identified patients with RIUSs. Five major reconstruction techniques were utilized: end-to-end (anastomosing the bladder to the transected ureter) and side-to-side (anastomosing the bladder to an anterior ureterotomy proximal to the stricture without ureteral transection) ureteral reimplantation, buccal or appendiceal mucosa graft ureteroplasty, appendiceal bypass graft, and ileal ureter interposition. When necessary, adjunctive procedures were performed for mobility (i.e., psoas hitch) and improved vascularity (i.e., omental wrap). Outcomes of surgery were determined by the absence of flank pain (clinical success) and absence of obstruction on imaging (radiological success). Results: A total of 32 patients with 35 ureteral units underwent RUR with a median stricture length of 2.5 cm (interquartile range [IQR] 2-5.5). End-to-end and side-to-side reimplantation techniques were performed in 21 (60.0%) and 8 (22.9%) RUR cases, respectively, while 4 (11.4%) underwent an appendiceal procedure. One patient (2.9%) required buccal mucosa graft ureteroplasty, while another needed an ileal ureter interposition. The median operative time was 215 minutes (IQR 177-281), estimated blood loss was 100 mL (IQR 50-150), and length of stay was 2 days (IQR 1-3). One patient required repair of a small bowel leak. Another patient died from a major cardiac event and was excluded from follow-up calculations. At a median follow-up of 13 months (IQR 9-22), 30 ureteral units (88.2%) were clinically and radiologically effective. Conclusion: RUR can be performed in patients with RIUSs with excellent outcomes. Surgeons must be prepared to perform adjunctive procedures for mobility and improved vascularity due to poor tissue quality. Repeat procedures for RIUSs heighten the risk of necrosis and failure.

Role of minimally invasive partial nephrectomy in the management of renal mass.

Partial nephrectomy is recommended for surgical management of small renal masses (SRM), or lesions ≤7 cm. The decision for surgical intervention involves a balanced patient assessment. Minimally invasive approach, which includes laparoscopic and robotic techniques, has shown to have improved blood loss, length of hospitalization, and post-operative pain while maintaining oncologic efficacy when compared to an open approach. Transperitoneal approach is preferred at most centers; however, retroperitoneoscopic minimally invasive surgery (MIS) partial nephrectomy expertise is essential for comprehensive kidney cancer care. With advances in surgical technology and deep penetration of robotics into surgical training and practice, robotic partial nephrectomy has become the modality of choice in modern clinical practice. This review discusses the indications and outcomes for various minimally invasive approaches of partial nephrectomy.

Robot-assisted distal ureteral reconstruction for benign pathology: Current state.

Distal ureteral reconstruction for benign pathologies such as stricture disease or iatrogenic injury has posed a challenge for urologist as endoscopic procedures have poor long-term outcomes, requiring definitive open reconstruction. Over the past decade, there has been an increasing shift towards robot-assisted laparoscopy (RAL) with multiple institutions reporting their outcomes. In this article, we reviewed the current literature on RAL distal ureteral reconstruction, focusing on benign pathologies only. We present peri-operative data and outcomes on the most common technique, ureteral reimplantation, as well as adjunct procedures such as psoas hitch and Boari flap. Additionally, we present alternative techniques reported in the literature with some technical considerations. Lastly, we describe the outcomes of the comparative studies between open, laparoscopy, and RAL. Although the body of literature in this field is limited, RAL reconstruction of the distal ureter appears to be safe, feasible, and with some advantages over the traditional open approach.

Pancreatic α-cell specific deletion of mouse Arx leads to α-cell identity loss.

The specification and differentiation of pancreatic endocrine cell populations (α-, ß-, δ, PP- and ε-cells) is orchestrated by a combination of transcriptional regulators. In the pancreas, Aristaless-related homeobox gene (Arx) is expressed first in the endocrine progenitors and then restricted to glucagon-producing α-cells. While the functional requirement of Arx in early α-cell specification has been investigated, its role in maintaining α-cell identity has yet to be explored. To study this later role of Arx, we have generated mice in which the Arx gene has been ablated specifically in glucagon-producing α-cells. Lineage-tracing studies and immunostaining analysis for endocrine hormones demonstrate that ablation of Arx in neonatal α-cells results in an α-to-ß-like conversion through an intermediate bihormonal state. Furthermore, these Arx-deficient converted cells express ß-cell markers including Pdx1, MafA, and Glut2. Surprisingly, short-term ablation of Arx in adult mice does not result in a similar α-to-ß-like conversion. Taken together, these findings reveal a potential temporal requirement for Arx in maintaining α-cell identity.