Adjuvant chemotherapy after radical cystectomy: Do all patients who need chemotherapy after surgery actually receive it?

Background: Compliance with the guideline recommendations for neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer is incomplete. The adjuvant chemotherapy approach has the advantage of pathology-based decision-making, allowing for patient selection. In addition, radical surgery is not delayed and treatment-related toxicity does not impair surgical fitness. The proportion of patients who completed chemotherapy after cystectomy among those who were fit and in need of treatment were evaluated. The reasons for not completing adjuvant chemotherapy were determined. Materials and methods: We retrospectively evaluated all patients who had undergone radical cystectomy at our center over the last 7 years. Indications for adjuvant chemotherapy included pathological T > 2, any node+, or surgical margin involvement. Only patients who were fit for chemotherapy before surgery were included in the study. Results: Of the 52 patients with muscle-invasive bladder cancer, 14 received neoadjuvant chemotherapy or unfit for chemotherapy were excluded. Of the remaining 38 patients, 14 (37%) had bladder-confined cancers and did not require additional chemotherapy. Of the 24 patients who needed chemotherapy and were fit to receive it, 8 patients completed treatment (33%), and 3 discontinued treatment due to toxicity. Twelve patients (50%) declined chemotherapy, whereas 1 patient became unfit for chemotherapy after surgery. Conclusions: While the adjuvant chemotherapy approach could save unnecessary treatment in 37% of patients, two-thirds of those who needed chemotherapy did not complete it. Patient refusal was the primary reason for not receiving treatment.

The Impact of Radiographic, Metabolic and Demographic Characteristics on Kidney Stone Recurrence.

Urolithiasis is a frequent disease with cited rates of recurrence after initial diagnosis that vary widely and range between 35% and 50%. We assessed the radiographic recurrence rate in patients with urinary stones and its risk factors. We retrospectively identified patients who were diagnosed with urinary stones on non-contrast computed tomography from 2010 to 2011, and underwent another imaging examination at least six months afterwards. We collected patient demographic, clinical, laboratory and radiologic data and compared patients with and without urinary stone recurrence. Ultimately, 237 patients were included in the study; the mean follow-up was 6.7 years; 88 patients (37.1%) had recurrence based on our recurrence criteria. On univariate analysis, the significant parameters for recurrence were baseline serum calcium and uric acid, stone location in the kidney, surgical intervention and stone burden volume. On multivariate analysis, surgical intervention (OR 3.07, p = 0.001), baseline calcium (OR 2.56, p = 0.011), baseline uric acid (OR 1.30, p = 0.021) and stone location in the kidney (OR 2.16, p = 0.012) were associated with higher risk of recurrence. These findings may guide personalized follow-up protocols for patients with urolithiasis based on their risk factors.

Potential Markers to Reduce Non-Contrast Computed Tomography Use for Symptomatic Patients with Suspected Ureterolithiasis.

Most patients with ureterolithiasis are managed successfully with conservative treatment. In this context, delineation of clinical risk factors that identify patients with low risk for surgical intervention may reduce use of Non-Contrast Computed Tomography (NCCT). Here, emergency department patient files from a 14-month period were reviewed retrospectively, to identify patients who underwent NCCT and showed a ureteral stone. Demographic, clinical and laboratory information was collected. Patients were grouped to either requiring surgical intervention (Group 1) or having successful conservative management (Group 2). The cohort included 368 patients; 36.1% ultimately required surgical intervention (Group 1) and 63.9% were successfully treated conservatively (Group 2). On univariate analysis, patients who required surgical intervention were older, had longer duration of symptoms, had history of urolithiasis and surgical intervention for urolithiasis and had higher serum creatinine levels. Multivariate analysis identified the following risk factors associated with surgical intervention: creatinine >1.5 mg/dL, duration of symptoms ≥ 1.5 days and age > 45 years. Patients with 0, 1, 2 or 3 of the identified risk factors had 19%, 32%, 53% and 73% likelihood, respectively, of surgical intervention. Incorporating these data may reduce the use of NCCT scans in patients who are likely to pass a stone via conservative management.

Design of a fully intraureteral stent and proof-of-concept in vivo evaluation.

Background: Ureteral stents are employed regularly to facilitate urine drainage and ureteral healing in a wide variety of endourological procedures, associated mainly with ureteral stone obstruction. However, stent use frequently impairs patient quality of life, which is generally attributed to the presence of anchoring stent curls in the bladder and/or kidney. The purpose of this study was to examine the potential effectiveness and safety of a newly designed, fully intraureteral stent, in an initial proof-of-concept in vivo evaluation. Methods: "Yoticurl" stents were synthesized from copolymeric, commercially-available ureteral stents. A first test to confirm the intended expansion of the spiral curls in a ureter was performed on a pig cadaver. Subsequently, a preliminary in vivo evaluation in a single pig model was completed to test stent viability, over a period of 25 days. Two stents were inserted to fully intraureteral positions into the two ureters, by standard human endourological procedure. Daily observational checks of the pig, and regular radiographic analyses were performed; the animal was then euthanized and examined by explorative laparotomy, followed by histological analysis of kidney, ureter and bladder tissue samples. Results: The pig displayed normal activity, appetite and sleep patterns, and radiography indicated free flow of urine, and no significant stent migration nor anatomical abnormalities. Subsequent histology found only mild inflammation in the ureter. Conclusions: The innovative stent design tested here, if ultimately proven safe and effective for human use, may offer an alternative to currently available stents for multiple indications.

Magnetic resonance imaging of in vitro urine flow in single and tandem stented ureters subject to extrinsic ureteral obstruction.

OBJECTIVE: To quantify the relative volumetric flows in stent and ureter lumina, as a function of stent size and configuration, in both unobstructed and externally obstructed stented ureters. METHODS: Magnetic resonance imaging was used to measure flow in stented ureters using a phantom kidney model. Volumetric flow in the stent and ureter lumina were determined along the stented ureters, for each of four single stent sizes (4.8F, 6F, 7F, and 8F), and for tandem (6F and 7F) configurations. Measurements were made in the presence of a fully encircling extrinsic ureteral obstruction as well as in benchmark cases with no extrinsic ureteral obstruction. RESULTS: Under no obstruction, the relative contribution of urine flow in single stents is 1-10%, while the relative contributions to flow are ~6 and ~28% for tandem 6F and 7F, respectively. In the presence of an extrinsic ureteral obstruction and single stents, all urine passes within the stent lumen near the extrinsic ureteral obstruction. For tandem 6F and 7F stents under extrinsic ureteral obstruction, relative volumetric flows in the two stent lumina are ~73% and ~81%, respectively, with the remainder passing through the ureter lumen. CONCLUSIONS: Magnetic resonance imaging demonstrates that with no extrinsic ureteral obstruction, minimal urine flow occurs within a stent. Stent lumen flow is significant in the presence of extrinsic ureteral obstruction, in the vicinity of the extrinsic ureteral obstruction. For tandem stents subjected to extrinsic ureteral obstruction, urine flow also occurs in the ureter lumen between the stents, which can reduce the likelihood of kidney failure even in the case of both stent lumina being occluded.

Drainage of infected kidneys with ureteral stents: does size matter?

PURPOSE: The purpose of our study was to evaluate the ability of ureteral stents with different diameters to drain pus that accumulates in an obstructed kidney using an in vitro model. METHODS: We developed an in vitro model of an obstructed kidney filled with pus. The model included a silicon kidney unit based on computed tomography (CT) data, a 3D printed ureteral stone based on a real extracted ureteral stone, a latex ureter model, a bladder vessel, and a fluid with qualities resembling pus. Identical printed stones were inserted into four ureter models containing stents with varying diameters (4.8F, 6F, 7F, 8F), each of which was connected to the kidney unit and the bladder vessel. The kidney unit was filled with artificial pus to pressures of 30 cmH2O to simulate an infected and obstructed kidney. The obstruction was relieved with stents in place, while artificial urine was pumped into the kidney; pressure in the kidney and remaining pus were measured continuously. RESULTS: The rate of pressure drop and the final pressure measured in the kidney were unaffected by the diameter of the stent. For all stent diameters, the pressure reached non-obstructed levels within 30 s, final pressure was reached within 90-120 s, and minimal amounts of pus remained in the kidney after 120 min. CONCLUSIONS: In vitro experiments demonstrate that all stent diameters drain pus-filled, obstructed kidneys with the same efficacy. The common perception that larger diameter tubes are more effective under such circumstances should be re-examined.

Imaging and Chemical Analysis of External and Internal Ureteral Stent Encrustation.

Introduction: Ureteral stents are effective in alleviating flow disruptions in the urinary tract, whether due to ureteral stones, strictures or extrinsic ureteral obstruction. However, significant stent encrustation on the external and/or internal stent lumen walls can occur, which may interfere with stent functioning and/or removal. Currently, there is only limited, generally qualitative, information on the distribution, mineral structure, and chemical content of these deposits, particularly in terms of stent lumen encrustation. Objective: To quantify, in an initial investigation, external and internal encrustation in representative, intact ureteral stents. The study investigates possible correlations between patterns of external and internal encrustation, determines mineral structure and chemical composition, and examines the potential for stent lumen obstruction even in the absence of external stent wall encrustation. Study Design: High-resolution, laboratory micro-computed tomography (micro-CT) was used to non-destructively image external and internal stent encrustation in four representative stents. X-ray diffractometry (XRD) and scanning electron microscopy-energy dispersive x-ray spectroscopy (SEM-EDS) enabled parallel analysis of mineral structure and chemical content of samples collected from external and internal encrusted material along the distal, proximal and mid-ureteral stent regions. Results: Extensive stent lumen encrustation can occur within any region of a stent, with only incidental or minor external encrustation, along the entire length of the stent. External and internal encrusted materials in a given stent are generally similar, consisting of a combination of amorphous (mostly organic) and crystalline mineral deposits. Conclusion: Micro-CT demonstrates that significant stent lumen encrustation can occur, which can lead to partial or full stent lumen occlusion, even when the exterior stent wall is essentially free of encrusted material.

When should we give up on expectant management for patients with proximal ureteral stones?

Background: Proximal ureteral stones (PUS) have relatively low rates of spontaneous expulsion. However, some patients do well on expectant management. Our aim was to compare risk factors for surgical intervention in patients with PUS who underwent primary intervention to those subjected to expectant management. Materials and methods: We retrospectively reviewed the medical charts of patients presented to the emergency room with symptoms of renal colic and underwent computerized tomography between August 2016 and August 2017. A total of 97 consecutive patients were identified with up to 10mm PUS. We collected patient demographics, clinical, and imaging data, and performed binary regression analysis for risk of intervention. Results: The average age was 49years (range 17-97) and average stone size was 7.1mm (range 3-10). Forty-one patients underwent immediate intervention while the remaining 56 patients were treated conservatively. Of the 56 patients treated conservatively, 26 underwent delayed intervention while 30 reported spontaneous stone expulsion. On univariate analysis of all 97 patients, statistically significant risk factors for intervention were found based on stone size, age, serum lymphocyte, platelet counts, and stone density. Of these risk factors, stone size ≥ 7mm (p = 0.012, odds ratio = 5.4) and platelet count ≤ 230K/µL (p = 0.027, odds ratio = 4.9) remained statistically significant on multivariate analysis. Conclusion: Stone size and platelet count were found to be risk factors for surgical intervention in patients with up to 10mm PUS. These findings may assist in identifying patients who are more suitable for conservative approach.

Influence of Single Stent Size and Tandem Stents Subject to Extrinsic Ureteral Obstruction and Stent Occlusion on Stent Failure.

Background and Purpose: Drainage of obstructed kidney attributable to extrinsic ureteral obstruction (EUO), required to prevent renal damage, is often achieved using Double-J ureteral stents. However, these stents fail frequently, and there is considerable debate regarding what stent size, type, and configuration offer the best option for sustained drainage. In this study, we examine the impact of stent diameter and choice of single/tandem configuration, subject to EUO and various degrees of stent occlusion, on stent failure. Materials and Methods: Computational fluid dynamics simulations and an in vitro ureter-stent experiment enabled quantification of flow behavior in stented ureters subject to EUO and stent occlusions. Various single and tandem stents under EUO were considered. In each simulation and experiment, changes in renal pressure were monitored for different degrees of stent lumen occlusion, and onset of stent failure as well as simulated distributions of fluid flow between stent and ureter lumina were determined. Results: For an encircling EUO that completely obstructs the ureter lumen, with or without partial stent occlusion, the choice of stent size/configuration has little effect on renal pressure. The pressure increases significantly for ∼90% stent lumen occlusion, with failure at >95% occlusion, independent of stent diameter or a tandem configuration, and with little influence of occlusion length along the stent. Conclusions: Stent failure rate is independent of stent diameter or single/tandem configuration, for the same percentage of stent lumen occlusion, in this model. Stent failure incidence may decrease for larger diameter stents and tandem configurations, because of the larger luminal area.

Surgical Outcomes in High-risk Prostate Cancer and Salvage Radical Prostatectomy.

BACKGROUND: Patients with high-risk prostate cancer are at higher risk of treatment failure, development of metastatic disease, and mortality. There is no consensus on the treatment of choice for these patients, and either radical prostatectomy (RP) or external beam radiation therapy (EBRT) is recommended. Surgery is less common as the initial treatment for high-risk patients, possibly reflecting the concerns regarding morbidity as well as oncological and functional outcomes. Another high-risk group includes patients with failure of previous EBRT or focal treatment. For these patients, salvage radical prostatectomy (SRP) can be offered. OBJECTIVES: To describe our experience with surgery of high-risk patients and SRP. METHODS: This cohort included all high-risk patients undergoing RP or SRP at our institution between January 2012 and December 2019. We reviewed the electronic medical charts and collected pathological, functional, and oncological outcomes. RESULTS: Our cohort included 39 patients; average age was 67.8 years, and average follow-up duration was 40.9 months. The most common postoperative morbidity was transfusion of packed cells. There were no life-threatening events or postoperative mortality. Continence was preserved (zero to one pad) in 76% of the patients. Twenty-three patients (59%) had undetectable prostate specific antigen levels following the surgery, 11 (30%) were treated with either adjuvant or salvage EBRT, and 12 patients (31%) were found with no evidence of disease and no additional treatment was needed. CONCLUSIONS: Radical prostatectomy and SRP are safe options for patients presenting with high-risk prostate cancer, with good functional and oncological outcomes.