Clips Can be Safely Used for Vascular Control of the Renal Vessels During Laparoscopic Donor Nephrectomy.

OBJECTIVE: To review our experience using clips to control the renal vessels during laparoscopic donor nephrectomy (LDN) and determine the safety of this practice. METHODS: We performed a retrospective review of patients who underwent LDN at our centre January 1, 2007-September 17, 2019. The primary outcome was the rate of complication associated with vascular control of the renal vessels, which included (1) conversion to open to manage bleeding, (2) additional procedures for bleeding, and (3) major bleeding requiring blood transfusion. Secondary outcomes included the rate of renal artery/vein clip dislodgement or crossing, change in hemoglobin, warm ischemia time and the incidence of intra-operative complications and postoperative in-hospital complications. RESULTS: We included 503 patients who underwent LDN, of which 497 were left sided. The main renal artery was controlled with 3 titanium clips in 489 (97%) cases. The main renal vein was controlled with 2 polymer-locking clips in 478 (95%) cases. For our primary outcome, there were no conversions to open to manage bleeding, no secondary procedures due to bleeding and no major bleeding requiring blood transfusion. Additionally, there were no donor deaths. Regarding our secondary outcomes, there were 5 intraoperative events related to the titanium clips being placed on the renal artery and 1 intraoperative event related to the polymer-locking clips on the renal vein, none of which resulted in any morbidity. CONCLUSION: Using 3 titanium clips on the renal artery and 2 polymer-locking clips on the renal vein during left LDN is safe and provides excellent vascular control.

Are Routine Laboratory Investigations Necessary Following Percutaneous Nephrolithotomy?

OBJECTIVE: To determine how effective routine postoperative blood work is in identifying complications after percutaneous nephrolithotomy (PCNL), the gold standard treatment for large volume stone disease. Although major complication rates are low, hemorrhagic and sepsis-related complications are serious and can occur. Routine post-PCNL complete blood count is routinely performed by most endourologists but may be a low-value practice. METHODS: A retrospective review was performed of all PCNL procedures at our center over a 3-year period. Patient demographic, stone characteristics and postoperative data were collected and analyzed. RESULTS: Three hundred and eighty-five patients (196 female and 189 males) underwent PCNL for the treatment of urolithiasis. Mean age was 55.8 years and mean length of stay in hospital was 1.74 days. Most patients (82.9%) had neither ureteric stent nor percutaneous tube prior to PCNL. Postoperatively, 4 patients (1.0%) required a blood transfusion and 14 patients (3.6%) developed urosepsis. Patients who required either a transfusion or developed urosepsis demonstrated abnormal vital signs (tachycardia, hypotension, or fever) postoperatively. Sixteen patients (4.2%) had normal vital signs but had an extended hospital stay only to monitor abnormal blood work results. None these patients required a transfusion nor developed urosepsis but had a length of stay that was a mean of 1.5 days longer patients with normal postoperative vital signs and blood work. CONCLUSION: Abnormal vital signs alone identified all patients that required transfusion or treatment for urosepsis after PCNL. Routine complete blood count testing postoperatively may not improve detection of infectious or bleeding complications and may prolong hospital admission unnecessarily.

Dual usage of a stone basket: Stone capture and retropulsion prevention.

INTRODUCTION: Stone migration during ureteroscopy (URS) for proximal ureteric calculi is a constant challenge. Several retropulsion prevention devices have been developed to optimize URS outcomes. Our technique involves capturing the stone within a four-wire Nitinol stone basket and then performing laser lithotripsy to dust the stone while it is engaged in the basket. The dusted fragments wash out with the irrigation fluid and once small enough, the remaining stone is removed intact. METHODS: A retrospective chart review was performed of all proximal semi-rigid URS procedures for a solitary calculus (2000-2016). We compared our new technique introduced in 2010 to URS control procedures that did not use retropulsion prevention techniques or devices. RESULTS: One hundred and forty patients underwent URS for proximal ureteric calculi. Mean stone diameter was 9.3±3.4 mm, with similar impaction rate between both groups (44.1% vs. 43.1% control; p=n/s). The mean surgical procedure time was 53.3±17.9 minutes for the new technique and 65.2±29.2 minutes for the control group (p=0.005). Compared to the new technique, the control group had a higher rate of retropulsion (33.3% vs. 14.7%; p=0.01) and required flexible URS more often to exclude or remove residual fragments (24.1% vs. 59.1%; p=0.001). Using the new technique, stone-free rates were higher (79.1% vs. 69.4%; p=n/s) and there was a lower likelihood of leaving residual fragments both <3 mm and ≥3 mm (p=0.001). CONCLUSIONS: Our novel technique results in shorter operative times, lower retropulsion rates, and decreases postoperative residual stone fragments.

Shockwave lithotripsy: techniques for improving outcomes.

OBJECTIVES: Shock wave lithotripsy (SWL) remains the only effective truly non-invasive treatment for nephrolithiasis. While single-treatment success rates may not equal those of ureteroscopy and percutaneous nephrolithotomy, it has an important role to play in the management of stones. In this paper, we outline the latest evidence-based recommendations for maximizing SWL outcomes, while minimizing complications. MATERIALS AND METHODS: A comprehensive review of the current literature was performed regarding maximizing SWL outcomes. RESULTS: Several different considerations need to be made regarding patient selection with respect to body habitus, body mass index, anatomical location and underlying urologic abnormalities. Stone composition and stone density (Hounsfield Units) are important prognostic variables. Patient positioning is critical to allow for adequate stone localization with either fluoroscopy or ultrasound. Coupling should be optimized with a low viscosity gel applied to the therapy head first and patient movement should be limited. SWL energy should be increased slowly and shockwave rates of 60 or 90 Hz should be used. Medical expulsive therapy with alpha-blockers after SWL treatment has shown benefit, particularly with stones greater than 10 mm. CONCLUSION: While single-treatment success rates may not equal those of ureteroscopy or percutaneous nephrolithotomy, with proper patient selection, optimization of SWL technique, and use of adjunctive treatment after SWL, success rates can be maximized while further reducing the already low rate of serious complications. SWL remains an excellent treatment option for calculi even in 2017.

Stone technology: intracorporeal lithotripters.

PURPOSE: Intracorporeal lithotripsy is becoming the most commonly used surgical method of stone treatment in Urology. The five major types of intracorporeal lithotripters are ultrasonic, ballistic, and combination lithotripters as well as laser and electrohydraulic lithotripters. The advantages and disadvantages of choosing each of these treatment modalities are reviewed. METHODS: Extensive review of literature was performed to identify the types of intracorporeal lithotripters. An investigation was undertaken of the early development of each modality of intracorporeal lithotripsy and/or the mechanism of action. Challenges of each technique were identified and presented. Finally, a determination was made of how these lithotripters compare on the basis of effectiveness of action and cost based on information provided in primary literature as well as previous reviews of these modalities. RESULTS: Contemporary lithotripters have found widespread use in the management of urinary lithiasis. Holmium laser lithotripsy has become one of the most commonly used tools for intracorporeal lithotripsy. CONCLUSION: There is a wide variety of intracorporeal lithotripters which can be chosen based on the characteristics of each modality and the requirements of the urologist.

Ureteroscopy with conscious sedation for distal ureteric calculi: 10-year experience.

INTRODUCTION: Distal ureteroscopy for stone extraction is a common procedure that is generally performed with spinal or general anesthesia. We retrospectively reviewed all distal ureteroscopy performed for ureteric stone extraction with conscious sedation at our institution over a 10-year period to determine its efficacy and safety. METHODS: A retrospective chart review was performed of all distal ureteroscopy performed for calculus removal from 2004 to 2014. Patient characteristics, analgesic requirement, tolerability, procedure time, stone size and composition, method of stone extraction, success rate, and complications were collected. RESULTS: Between 2004 and 2014, 314 procedures were performed. Mean age was 53.74 years, with 160 males and 154 females. A success rate of 97% and 10 (3.2%) complications were reported. Mean analgesic requirement was 189 µg of fentanyl (range: 50-400) and 2.79 mg of midazolam (range: 0-8). A total of 263 patients (83.7%) tolerated the procedure well, with only seven (2.2%) having poor tolerability. When comparing females to males, females were found to require less fentanyl (p=0.0001) and midazolam (p=0.0001). When calculi >5 mm were compared to those <5 mm, there was no statistically significant difference in success rate, procedure time, analgesic requirement, tolerability, or complications. CONCLUSION: Distal ureteroscopy with conscious sedation is safe and efficacious. To our knowledge, this is the first report demonstrating stones >5 mm can be safely and effectively treated with conscious sedation during this procedure. The context of our findings must be understood within the limitations of our retrospective analysis.

Salvage HIFU for biopsy confirmed local prostate cancer recurrence after radical prostatectomy and radiation therapy: Case report and literature review.

High-intensity focused ultrasound (HIFU) is a treatment option for low- and intermediate-risk prostate cancer and more recently has been used as salvage therapy after failed radiation therapy. We present a case of local recurrence with biochemical failure after radical prostatectomy and salvage external beam radiation therapy with salvage HIFU without biochemical recurrence at 20 months.

Small Cell Cancer of the Bladder and Prostate: A Retrospective Review from a Tertiary Cancer Center.

BACKGROUND:  Genitourinary small cell cancer (GUSCC) is a rare malignancy. Most of the published data on how to manage this malignancy is based on institutional experience. We undertook the current retrospective review to determine the outcome of the patients with GUSCC treated at CancerCare Manitoba, Canada over a period of 18 years. METHODS: The Manitoba Cancer Registry was used to identify patients with a confirmed pathological diagnosis of small cell cancer (SCC) of the bladder or prostate between January 1, 1995, and October 31, 2013. RESULTS:  There were 42 patients identified, 28 bladder SCC (17 limited, 11 extensive stage) and 14 prostate SCC (one limited, 12 extensive, and one unknown stage). The median age was 70.7 years. There were 22 patients who were treated with chemotherapy and radiation, five received radiation only, four received chemo only, nine did not receive any treatment, one patient had surgery only, and one had surgery and radiation. The median and one-year overall survival for all patients was 10.7 months and 43%. The median and one-year overall survival of SCC of the bladder was 55.1 months and 71% for the limited stage and 10.1 months and 36% for the extensive stage. The median and one-year overall survival for extensive stage SCC of the prostate was 4.1 months and 17%. There was only one patient with limited stage SCC of the prostate who did not receive any treatment and died of progressive disease 11 months from diagnosis. CONCLUSIONS:  Our findings suggest that patients with limited stage SCC of the bladder can have a surprisingly good outcome with multimodality treatment. The outcome of the patients with extensive stage SCC of the bladder and prostate remains dismal and optimal therapeutic options have yet to be determined.

Multiple secondary malignancies following radiation therapy for testicular cancer.

Testicular germ cell tumours (TGCT) are a rare malignancy that affect primarily young men. We present an interesting case of non-seminoma testicular cancer treated with external beam radiation therapy (RT), which subsequently resulted in two separate secondary malignancies decades after initial treatment.

Leiomyosarcoma of the inferior vena cava with renal metastasis: An unusual case and diagnostic challenge.

Leiomyosarcomas are exceedingly rare malignant tumours with a very poor prognosis. We present a 78-year-old patient with a small renal and paracaval mass. Surgery included right open partial nephrectomy and resection of the paracaval mass to treat the presumed renal cell carcinoma. Pathology revealed the tumour to be leiomyosarcoma (LMS). This is only the second documented report of an inferior vena cava LMS presenting along with an ipsi-lateral renal mass.

Hidden penile squamous cell carcinoma: A case report.

Penile cancer is a rare malignancy that typically presents as a superficial lesion. We present an interesting case of subepithelial penile cancer presenting without superficial manifestation.

Renal primitive neuroectodermal tumour: Case series and brief review.

Renal primitive neuroectodermal tumor is a rare malignancy. These tumours rarely present with caval involvement. We report 2 cases of primitive neuroectodermal tumours (PNETs) with inferior vena cava involvement. The initial presentation and outcomes differed significantly. The diagnosis was confirmed using histologic and pathologic analysis. We present a brief literature review and an outline of typical clinical and pathologic features of renal PNETs.

Brevinin-2R(1) semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway.

Brevinin-2R is a novel non-hemolytic defensin that was isolated from the skin of the frog Rana ridibunda. It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T-cell leukemia), BJAB (B-cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF-7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells including peripheral blood mononuclear cells (PBMC), T cells and human lung fibroblasts. Jurkat and MCF-7 cells overexpressing Bcl2, and L929 and MCF-7 over-expressing a dominant-negative mutant of a pro-apoptotic BNIP3 (DeltaTM-BNIP3) were largely resistant towards Brevinin-2R treatment. The decrease in mitochondrial membrane potential (DeltaPsim), or total cellular ATP levels, and increased reactive oxygen species (ROS) production, but not caspase activation or the release of apoptosis-inducing factor (AIF) or endonuclease G (Endo G), were early indicators of Brevinin-2R-triggered death. Brevinin-2R interacts with both early and late endosomes. Lysosomal membrane permeabilization inhibitors and inhibitors of cathepsin-B and cathepsin-L prevented Brevinin-2R-induced cell death. Autophagosomes have been detected upon Brevinin-2R treatment. Our results show that Brevinin-2R activates the lysosomalmitochondrial death pathway, and involves autophagy-like cell death.

The emerging importance of DNA mapping and other comprehensive screening techniques, as tools to identify new drug targets and as a means of (cancer) therapy personalisation.

Every human being is genetically unique and this individuality is not only marked by morphologic and physical characteristics but also by an individual's response to a particular drug. Single nucleotide polymorphisms (SNPs) are largely responsible for one's individuality. A drug may be ineffective in one patient, whereas the exact same drug may cure another patient. Recent advances in DNA mapping and other screening technologies have provided researchers and drug developers with crucial information needed to create drugs that are specific for a given individual. In the future, physicians will be able to prescribe individualised drugs adjusted to, for example, activities of specific enzymatic pathways that would either be targeted by these drugs, or would be responsible for drug conversion or inactivation. Furthermore, the mapping of the human genome allows broader development and application of drugs that act on the level of gene transcription rather than as simple biochemical inhibitors or activators of certain enzymes. Such new approaches will maximise desired therapeutic results and may completely eliminate severe side effects. To illustrate the potential of genetic translational research, the authors discuss available analytical methodologies such as; gene arrays, flow cytometry-based screening for SNPs, proteomics, metabolomics, real-time PCR, and other methods capable of detecting both SNPs, as well as more profound changes in cell metabolism. Finally, the authors provide several examples that focus mostly on targeting protein-DNA interactions, but also other processes.

Caspases and cancer: mechanisms of inactivation and new treatment modalities.

Elimination of superfluous or mutated somatic cells is provided by various mechanisms including apoptosis. Deregulation of apoptotic signaling pathways may contribute to oncogenesis. Aspartate specific cysteine proteases, termed caspases are the key effector molecules in apoptosis. The aim of this review is to summarize the various defects in caspase-dependent cell death machinery identified in the neoplastic cells. These include not only mutations, but also alterations of gene methylation, and altered mRNA stability. Among the molecules that we discuss are elements of the extrinsic death pathway like CD95 (APO-1/Fas), FADD, FLIPs, FLICE, other apical caspases, components of the intrinsic apoptotic pathway like Apaf-1, caspase-9, and modulators of apoptotic pathways like IAPs, Smac/DIABLO, OMI/HtrA2, and other apoptosis regulating proteins. We also discuss recent data on cancer-specific agents that target effector mechanisms of apoptosis. Particular emphasis is given to the prospects for combining cell suicide-activating approaches with classical cancer therapies.