Comparison of Superpulse Thulium Fiber Laser vs Holmium Laser for Ablation of Renal Calculi in an In Vivo Porcine Model.

Introduction and Objectives: We sought to compare the effectiveness and efficiency of the superpulse thulium fiber laser (sTFL to the holmium: yttrium-aluminum-garnet [Ho:YAG] laser for ureteroscopic "dusting" of implanted renal stones in an in vivo porcine model. Methods: Twenty-four porcine kidneys (12 juvenile female Yorkshire pigs) were randomized to Ho:YAG or sTFL treatment groups. Canine calcium oxalate stones were scanned with computed tomography to calculate stone volume and stone density; the stones were randomized and implanted into each renal pelvis via an open pyelotomy. In all trials, a 14F, 35 cm ureteral access sheath was placed. With a 9.9F dual lumen flexible ureteroscope, laser lithotripsy was performed using dusting settings: Ho:YAG 200 µm laser fiber at 16 W (0.4 J, 40 Hz) or sTFL 200 µm laser fiber at 16 W (0.2 J, 80 Hz). Lithotripsy continued until no fragments over 1 mm were observed. No stone basketing was performed. Throughout the procedures, intrarenal and renal pelvis temperatures were measured using two percutaneously positioned K-type thermocouples, one in the upper pole calyx and one in the renal pelvis. After the lithotripsy, the ureteropelvic junction was occluded, the kidneys were bivalved, and all residual fragments were collected, dried, weighed, and then measured with an optical laser particle sizer. Results: Implanted stones were similar in volume and density in both groups. Intraoperative collecting system temperatures were similar for both groups (all <44°C). Compared to Ho:YAG, sTFL ablated stones faster (9 vs 27 minutes, p < 0.001) with less energy expenditure (8 vs 26 kJ, p < 0.001), and a greater stone clearance rate (73% vs 45%, p = 0.001). After sTFL lithotripsy, 77% of the remaining fragments were ≤1 mm vs 17% of fragments ≤1 mm after Ho:YAG treatment (p < 0.001). Conclusions: In an in vivo porcine kidney, using dusting settings, sTFL lithotripsy resulted in shorter ablation times, higher stone clearance rates, and markedly smaller stone fragments than Ho:YAG lithotripsy.

Porcine Bladder Replacement with a Bilayer Silk Fibroin Enhanced Prosthetic Reservoir: A Feasibility Study.

Introduction: The creation of synthetic reservoirs for bladder replacement has been limited by challenges of interfacing synthetic materials and native tissue. We sought to overcome this challenge by utilizing a novel bilayer silk fibroin scaffold (BLSF) as an intermediary toward the development of an acellular prosthetic reservoir. Methods: Under institutionally approved protocols, 3D-printed reservoirs were implanted in six juvenile female pigs after cystectomy. BLSF was attached to the in situ prosthetic reservoir serving as an intermediary to native ureteral and urethral tissue anastomoses. Our first protocol allowed four pigs to be survived up to 7 days, and the second protocol allowed two pigs to be survived for up to 1 year. At the first sign of functional decline or the end of the study period, the animals were euthanized, and kidneys, ureters, prosthetic bladder, and urethra were harvested en bloc for histopathology analysis. Results: The first two pigs had anastomotic urine leaks because of design flaws resulting in early termination. The third pig had acute renal failure resulting in early termination. The artificial bladder design was modified in subsequent iterations. The fourth pig survived for 7 days and, upon autopsy, had intact urethral and ureteral anastomoses. The fifth and sixth pigs survived for 11 and 12 weeks, respectively, before they were sacrificed because of failure to thrive. One animal developed an enteric fistula. The other animal had an intact anastomosis, and the BLFS was identified at the ureteral and urethral anastomoses on histopathologic analysis. Conclusions: Replacing the porcine bladder with a prosthetic bladder was achieved for up to 3 months, the second longest survival period for a nonbiologic bladder alternative. BLSF was used for the first time to create an interface between synthetic material and biologic tissue by allowing ingrowth of urothelium onto the acellular alloplastic bladder.

The Impact of One Week of Pre-Stenting on Porcine Ureteral Luminal Circumference.

Objectives: Larger ureteral access sheaths (UASs) have the potential to improve ureteroscopic stone removal outcomes but are often avoided by surgeons because of concerns of ureteral injury. Using our novel UAS force sensor and previously defined force thresholds for ureteral injury, we sought to evaluate the impact of 1 week of stenting on the maximum safe dilation of ureteral luminal circumference. Methods: Twelve juvenile female Yorkshire pigs (24 ureters) were evaluated. The inner (i.e., luminal) circumference of each ureter was determined using Cook urethral dilators ranging from 8F to 24F in 2F increments, 37 cm in length. Each dilator was sequentially passed while applying the UAS force sensor to measure insertion force before and after 1 week of stent placement. Each ureter was randomized to receive either a 4.7F or 7.0F stent (20 cm). Maximum ureteral luminal circumference was defined as effective passage of the dilator to the ureteropelvic junction with ≤6 newtons (N) of force (the force threshold previously defined by porcine and clinical studies to avoid ureteral damage). After passage of the largest dilator at 6 N, flexible ureteroscopy was performed and a post-ureteroscopic lesion scale (PULS) was recorded. Results: After 1 week of stent placement, the median ureteral luminal circumference increased to 15F representing a mean increase of 3.8F ± 2.8F (p < 0.001). Twenty-one (88%) of the pre-stented ureters had an increase in luminal circumference, with 12 ureters (50%) dilated to ≥16F (p = 0.032), 6 ureters (25%) dilated to ≥18F, and in 2 cases a maximum size of 24F was recorded. The PULS grade was ≤2 in all cases, indicating no high-grade ureteral injuries. Laterality and stent size did not impact ureteral luminal circumference after pre-stenting (p = 0.232 and p = 0.337, respectively). Conclusions: One week of ureteral stenting resulted in nearly a 4F increase in the luminal circumference of porcine ureters.

Crowd-Sourced Assessment of Surgical Skills of Urology Resident Applicants: Four-Year Experience.

OBJECTIVE: To determine a) if surgical skills among urology resident applicants could be reliably assessed via crowdsourcing and b) to what extent surgical skills testing impacts resident selection. DESIGN: Interviewees completed the following surgical skills tasks during their interview day: open knot tying (OKT), laparoscopic peg transfer (LPT), and robotic suturing (RS). Urology faculty and crowd-workers evaluated each applicant's video-recorded performance using validated scoring and were assessed for agreement using Cronbach's alpha. Applicants' USMLE scores, interview scores, and Jefferson Scale of Physician Empathy (JSPE-S) scores were assessed for correlation with skills testing scores and match rank. Additionally, a survey was distributed to interviewees assessing match outcomes. SETTING: University of California Irvine Department of Urology, Surgical Skills Laboratory PARTICIPANTS: All 94 urology residency interviewees at the University of California Irvine Department of Urology from 2015-2018 were invited to complete the three surgical skills tasks on their interview day. RESULTS: Survey responses were received from all 94 interviewees (100%). Crowd and expert agreement was good (α=0.88), fair (α=0.67), and poor (α=0.32) for LPT, RS, and OKT scores, respectively. The skills testing scores did not correlate with match rank, USMLE score, or JSPE-S score. On multivariate analysis, only interview score (r= -0.723; p<0.001) and faculty LPT score (r=-0.262; p=0.001) were significant predictors of match rank. Interviewees who reported matching into a top 3 residency choice had significantly higher faculty LPT scores than those who did not (11.9 vs. 9.7, p=0.03). CONCLUSIONS: Surgical skills overall did not significantly impact match rank. Expert assessment of laparoscopic peg transfer skills and interview performance among urology resident applicants correlated with match rank.

In Vitro Evaluation of Stone Fragment Evacuation by Suction.

Introduction: Contemporary, flexible stone baskets are unable to extract submillimeter stone fragments at the time of ureteroscopic laser lithotripsy. In this in vitro study, the feasibility of suctioning submillimeter fragments with a standard Luer Lock syringe through the working channel of a flexible ureteroscope was assessed. Materials and Methods: Phantom stones made from industrial plaster were mechanically fragmented into ≤1 and ≤0.5-mm groups. Both stone groups were divided into five preweighed trial samples. Each stone group was then mixed in a beaker filled with normal saline. A standard 10-mL Luer Lock syringe was connected to a fiber-optic ureteroscope with a 1.2-mm working channel. The syringe was then used to suction stone fragments from the beaker. The suctioned stone fragments and the stone fragments remaining in the beaker after removing the overlying solution were separated, centrifuged with supernatant removed, and dried in an incubator set at 33°C for 1 week. Dried weights were recorded. Results: Mean total weights for ≤0.5 and ≤1.0-mm stone groups at baseline were 0.807 and 0.806 g, respectively. The mean percentages of stone fragments suctioned through the ureteroscope for ≤0.5 and ≤1.0-mm groups were 86% and 86%, respectively (p = 0.973). During suctioning, 64% of stones in the ≤0.5-mm group were trapped in either the working channel of the ureteroscope or within the Luer Lock syringe compared with 78% of stones in the ≤1-mm group (p = 0.001) requiring cessation of the procedure to clear the channel. Conclusions: It is feasible to suction submillimeter stone fragments by connecting a Luer Lock syringe to the working channel of a flexible ureteroscope. The limiting factor for removing stone fragments appears to be the small working channel of flexible ureteroscopes as trapping of fragments during suctioning is common and requires time-consuming removal of the endoscope and clearing of the channel.

Auricular Hemosiderosis in a Diabetic Patient.

A 74-year-old Caucasian man with poorly controlled diabetes and hypertension was seen in the dermatology clinic for treatment of a nodular basal cell carcinoma on his right temple. He had poorly controlled diabetes for decades and had been insulin dependent for 20 to 25 years. He had not been on any anticoagulation therapy in the past or present and had no history of a hematologic disorder. He was retired and did woodworking as a hobby. During a routine presurgical head and neck skin examination, he was noted to have macular bluegray dyspigmentation of the central portion of the anterior portion of his ear lobes, bilaterally (Figure 1). He had first noticed this color change approximately 2 years ago and thought the pigmentation was darkening. It was not symptomatic. A punch biopsy was obtained.

The Association of Mammographic Density and Molecular Breast Cancer Subtype.

Background: Mammographic density (MD) is associated with increased breast cancer risk, yet limited data exist on an association between MD and breast cancer molecular subtypes.Methods: Women ages 18 years and older with breast cancer and available mammograms between 2003 and 2012 were enrolled in a larger study on MD. MD was classified by the Breast Imaging Reporting and Data System (BI-RADS) classification and by volumetric breast percent density (Volpara Solutions). Subtype was assigned by hormone receptor status, tumor grade, and mitotic score (MS). Subtypes included: Luminal-A (ER/PR+ and grade = 1; ER/PR+ and grade = 2 and MS = 1; ER+/PR- and grade = 1; n = 233); Luminal-B (ER+ and grade = 3 or MS = 3; ER+/PR- and grade = 2; ER/PR+ and grade = 2 and MS = 2; n = 79); Her-2-neu+ (H2P; n = 59); triple-negative (ER/PR-, Her-2-; n = 86). Precancer factors including age, race, body mass index (kg/m2), family history of breast cancer, and history of lobular carcinoma in situ were analyzed.Results: A total of 604 patients had invasive cancer; 457 had sufficient information for analysis. Women with H2P tumors were younger (P = 0.011) and had the highest volumetric percent density (P = 0.002) among subgroups. Multinomial logistic regression (LA = reference) demonstrated that although quantitative MD does not significantly differentiate between all subtypes (P = 0.123), the association between MD and H2P tumors is significant (OR = 1.06; confidence interval, 1.01-1.12). This association was not seen using BI-RADS classification in bivariable analysis but was statistically significant (P = 0.047) when controlling for other precancer factors.Conclusions: Increased MD is more strongly associated with H2P tumors when compared with LA.Impact: Delineating risk factors specific to breast cancer subtype may promote development of individualized risk prediction models and screening strategies. Cancer Epidemiol Biomarkers Prev; 26(10); 1487-92. ©2017 AACR.

Hemophagocytic Lymphohistiocytosis in a Newborn Presenting as "Blueberry Muffin Baby".

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled activation and proliferation of proinflammatory cytokines. Initial presentation commonly includes fever, hepatosplenomegaly, and pancytopenia; 6 to 65% of cases also have a concurrent cutaneous eruption. We present the case of a 6-day-old premature infant boy with congenital severe thrombocytopenia, anemia, and hepatosplenomegaly who presented with several cutaneous violaceous papules and nodules and was found to have HLH.

Bleomycin-induced flagellate hyperpigmentation.

A 27-year old male with Hodgkin's lymphoma was treated with combined chemotherapy that included bleomycin. He presented with pruritic erythematous, edematous linear lesions and was diagnosed to have flagellate hyperpigmentation, a rare side effect of bleomycin chemotherapy.

Pagetoid Reticulosis: Report of Two Cases and Review of the Literature.

Pagetoid reticulosis is a rare variant of mycosis fungoides that presents with a large, usually single, erythematous, slowly growing scaly plaque containing an intraepidermal proliferation of neoplastic T lymphocytes. Histopathologically, this disease has distinctive attributes. In this report, we present two cases of pagetoid reticulosis, compare its microscopic features to those of 'classical' mycosis fungoides, and provide a brief review of the pertinent literature.

Hair Follicle Nevus Located on the Chin of an Infant: Case Report and Review of Literature.

Hair follicle nevi are rare, benign, congenital hamartomas that usually occur in the distribution of the first brachial arch. Histopathologically, the distinction between hair follicle nevus, trichofolliculoma, and accessory tragus has recently come into question, and it may be that they are all on a spectrum of the same condition. We report the case of a 7-day-old boy who presented with a "tag"-like lesion on his midline chin that had been present since birth. Biopsy of the lesion proved it to be a hair follicle nevus.

Does Mammographic Density have an Impact on the Margin Re-excision Rate After Breast-Conserving Surgery?

BACKGROUND: Limited and conflicting data exist on an association between mammographic density (MD) and re-excision rates after breast-conserving surgery (BCS). Additionally, the correlation of MD with resection of unnecessary margins during initial BCS is unknown. METHODS: All women with a diagnosis of breast cancer from 2003 to 2012 and enrolled in a larger study on MD were evaluated. Operative and pathology reports were reviewed to determine margin resection and involvement. Mammographic density was determined both by breast imaging-reporting and data system (BI-RADS) classification and by an automated software program (Volpara Solutions). Additional margins were deemed unnecessary if the lumpectomy specimen margin was free of invasive tumor [≥2 mm for ductal carcinoma in situ (DCIS)] or if further re-excision was needed. RESULTS: Of 655 patients, 398 (60.8%) had BCS, whereas 226 (34.5%) underwent initial mastectomy. The women with denser breasts (BI-RADS 3 or 4) underwent initial mastectomy more frequently than the women with less dense breasts (40.0 vs. 30.5%, respectively; p = 0.0118). Of the patients with BCS, 166 (41.7%) required separate re-excision. Additional margins were taken during BCS in 192 (48.2%) patients, with 151 (78.6%) proving to be unnecessary. In the bivariable analysis, the patients with denser breasts according to BI-RADS classification and volumetric density showed a trend toward requiring more frequent re-excision, but this association was not seen in the multivariable analysis. The rate of unnecessary margins did not differ by breast density. In the multivariate analysis, the re-excision rates increased with DCIS (p < 0.0003) and decreased with resection of additional margins (p = 0.0043). CONCLUSIONS: Mammographic density is not associated with an increased need for re-excision or resection of unnecessary margins at initial BCS.

Nephrogenic Systemic Fibrosis Manifesting a Decade After Exposure to Gadolinium.

IMPORTANCE: Nephrogenic systemic fibrosis (NSF) is a fibrosing skin disorder that develops in patients with kidney failure and has been linked to exposure to gadolinium-containing contrast agents. The time between exposure to gadolinium and the initial presentation of NSF is typically weeks to months but has been documented to be as long as 3½ years. We report a case of NSF developing 10 years after exposure to gadolinium. OBSERVATIONS: A long-term hemodialysis patient was exposed to gadolinium several times between 1998 and 2004 during magnetic resonance angiography of his abdominal vessels and arteriovenous fistula. In 2014, he was seen at our clinic with new dermal papules and plaques. Biopsy of affected skin showed thickening of collagen, CD34+ spindle cells, and increased mucin in the dermis, supporting the diagnosis of NSF. CONCLUSIONS AND RELEVANCE: The clinical history and histopathological features of this case support the diagnosis of NSF 10 years after exposure to gadolinium. Although the use of gadolinium contrast agents in patients with kidney failure has markedly decreased, patients with exposure to gadolinium years to decades previously may manifest the disease.

Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion.

The present study determined the differential effects of unilateral striatal dopamine depletion on cranial motor versus limb motor function. Forty male Long Evans rats were first trained on a comprehensive motor testing battery that dissociated cranial versus limb motor function and included: cylinder forepaw placement, single pellet reaching, vermicelli pasta handling; sunflower seed opening, pasta biting acoustics, and a licking task. Following baseline testing, animals were randomized to either a 6-hydroxydopamine (6-OHDA) (n=20) or control (n=20) group. Animals in the 6-OHDA group received unilateral intrastriatal 6-OHDA infusions to induce striatal dopamine depletion. Six-weeks following infusion, all animals were re-tested on the same battery of motor tests. Near infrared densitometry was performed on sections taken through the striatum that were immunohistochemically stained for tyrosine hydroxylase (TH). Animals in the 6-OHDA condition showed a mean reduction in TH staining of 88.27%. Although 6-OHDA animals were significantly impaired on all motor tasks, limb motor deficits were more severe than cranial motor impairments. Further, performance on limb motor tasks was correlated with degree of TH depletion while performance on cranial motor impairments showed no significant correlation. These results suggest that limb motor function may be more sensitive to striatal dopaminergic depletion than cranial motor function and is consistent with the clinical observation that therapies targeting the nigrostriatal dopaminergic system in Parkinson's disease are more effective for limb motor symptoms than cranial motor impairments.

Evaluating end-of-life care from the perspective of the patient's family.

This article is written from personal experiences with the recent death of the authors' mother. It highlights the problems the authors encountered, while acknowledging the positive aspects of treatment during a difficult time. The overall purpose is to improve end-of-life care by advancing policy through research, legislation, and education. The impetus for writing this article is personal experience, but its larger purpose is to address issues that many readers will face in the future and suggest possible reforms, especially in the area of education.