Examining the impact of postoperative opioid use on length of hospital stay following radical cystectomy.

INTRODUCTION: Radical cystectomy (RC) is associated with high rates of morbidity, prolonged hospital stay, and increased opioid use for postoperative pain management; however, the relationship between postoperative opioid use and length of stay (LOS ) remains uncharacterized. This study serves to investigate the association between postoperative opioid use and length of hospital stay after RC. The relationship between patient and surgical factors on LOS was also characterized. METHODS: We retrospectively reviewed all patients between 2009 and 2019 who underwent RC at our institution. Patient and perioperative variables were analyzed to determine the relationship between postoperative opioid use and LOS using multivariable linear regression analysis. RESULTS: We identified 240 patients for study inclusion with a median age of 70.0 years. Median LOS was 10.0 days, with median daily mg morphine equivalent use of 57.5 for patients. Daily mg morphine equivalent use was significantly associated with an increased LOS, as were previous pelvic radiation, postoperative ileus, and higher Clavien-Dindo grade complication during admission (all p<0.05). Median LOS increased by one day for each increase of 13.2 daily mg morphine equivalents received. CONCLUSIONS: Increased daily opioid use was associated with increased length of hospital stay after RC. Non-opioid-based pain management approaches may be effective in reducing LOS after RC.

Prolactin- and testosterone-induced carboxypeptidase-D correlates with increased nitrotyrosines and Ki67 in prostate cancer.

BACKGROUND: Carboxypeptidase-D (CPD) cleaves C-terminal arginine for conversion to nitric oxide (NO) by nitric oxide synthase (NOS). Prolactin (PRL) and androgens stimulate CPD gene transcription and expression, which increases intracellular production of NO to promote viability of prostate cancer (PCa) cells in vitro. The current study evaluated whether hormonal upregulation of CPD and NO promote PCa cell viabilty in vivo, by correlating changes in expression of CPD and nitrotyrosine residues (products of NO action) with proliferation marker Ki67 and associated proteins during PCa development and progression. METHODS: Fresh prostate tissues, obtained from 40 men with benign prostatic hyperplasia (BPH) or PCa, were flash-frozen at the time of surgery and used for RT-qPCR analysis of CPD, androgen receptor (AR), PRL receptor (PRLR), eNOS, and Ki67 levels. Archival paraffin-embedded tissues from 113 men with BPH or PCa were used for immunohistochemical (IHC) analysis of CPD, nitrotyrosines, phospho-Stat5 (for activated PRLR), AR, eNOS/iNOS, and Ki67. RESULTS: RT-qPCR and IHC analyses showed strong AR and PRLR expression in benign and malignant prostates. CPD mRNA levels increased ∼threefold in PCa compared to BPH, which corresponded to a twofold increase in Ki67 mRNA levels. IHC analysis showed a progressive increase in CPD from 11.4 ± 2.1% in benign to 21.8 ± 3.2% in low-grade (P = 0.007), 40.7 ± 4.0% in high-grade (P < 0.0001) and 50.0 ± 9.5% in castration-recurrent PCa (P < 0.0001). Immunostaining for nitrotyrosines and Ki67 mirrored these increases during PCa progression. CPD, nitrotyrosines, and Ki67 tended to co-localize, as did phospho-Stat5. CONCLUSIONS: CPD, nitrotyrosine, and Ki67 levels were higher in PCa than in benign and tended to co-localize, along with phospho-Stat5. The strong correlation in expression of these proteins in benign and malignant prostate tissues, combined with abundant AR and PRLR, supports in vitro evidence that the CPD-Arg-NO pathway is involved in the regulation of PCa cell proliferation. It further highlights a role for PRL in the development and progression of PCa.

Carboxypeptidase-D is elevated in prostate cancer and its anti-apoptotic activity is abolished by combined androgen and prolactin receptor targeting.

BACKGROUND: Carboxypeptidase-D (CPD) cleaves C-terminal arginine for nitric oxide (NO) production. CPD and NO levels are upregulated by testosterone (T) and prolactin (PRL) to promote survival of prostate cancer (pCa) cells. This study evaluated CPD immunostaining and T/PRL regulation of CPD and NO levels in benign and malignant prostate tissues/cells to determine the role of CPD in pCa. METHODS: Immunohistochemistry (IHC) and tissue microarrays (TMA) were used to determine CPD immunostaining in prostate specimens. QPCR and immunoblotting were used to quantify CPD mRNA/protein expression in prostate cells. NO production was measured using 4,5-diaminofluorescein diacetate assay. RESULTS: CPD staining increased from 8.9 ± 3.8% (Mean ± SEM, n = 15) of benign epithelial cell area to 30.9 ± 2.9% (n = 30) of tumor cell area in one set of TMAs (P = 0.0008) and from 5.9 ± 0.9% (n = 45) of benign epithelial cell area to 18.8 ± 1.9% (n = 55) of tumor area in another (P < 0.0001). IHC of prostate tissues (≥50 mm(2)) confirmed increased CPD staining, from 13.1 ± 2.9% in benign (n = 16) to 29.5 ± 4.4% in pCa (n = 31, P = 0.0095). T and/or PRL increased CPD expression in several pCa but not benign cell lines. T and PRL acted synergistically to increase NO production, which was abolished only when receptor antagonists flutamide and Δ1-9-G129R-hPRL were used together. CONCLUSIONS: CPD immunostaining and T/PRL-stimulated CPD expression were higher in pCa than benign tissues/cells. Elevated CPD increased NO production, which was abolished when both AR and PRLR were inhibited. Our study implicates a critical role for the T/PRL-stimulated CPD-Arg-NO pathway in pCa progression, and suggests that AR+PRLR inhibition is a more effective treatment for pCa.

The contemporary role of lymph node dissection during nephroureterectomy in the management of upper urinary tract urothelial carcinoma: the Canadian experience.

OBJECTIVE: To investigate the association between lymph node dissection (LND) and survival among patients undergoing nephroureterectomy for upper urinary tract urothelial cell carcinoma (UTUC). METHODS: This study includes 1029 patients from 10 Canadian institutions who underwent nephroureterectomy between 1990 and 2010. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were compared for patients with a node-negative LND (N0), node-positive LND (N+), or no LND (Nx) using Kaplan-Meyer analysis and Cox regression analysis. The association between survival and number of positive nodes, number of nodes removed, and ratio of positive nodes to nodes removed was also investigated. RESULTS: The median follow-up for the entire cohort was 19.8 months (interquartile range = 7.2-53.8). LND was performed in 276 (26.8%) patients, and 77 (27.9%) had N+ disease. Patients with N+ disease had significantly shorter OS, DSS, and RFS compared with N0 and Nx patients(P < .01). No differences were identified between N0 and Nx patients in any survival categories (P > .05). A ratio of positive nodes to nodes removed ≥ 20% had a per annum hazard ratio of 2.24 (95% confidence interval [CI] 1.18-4.65) for OS, 2.70 (95% CI = 1.25-5.83) for DSS, and 1.94 (95% CI = 1.13-3.32) for RFS. The number of positive nodes and the number of nodes removed were not associated with survival in any survival category (P > .05). CONCLUSION: LND during nephroureterectomy provides more accurate staging and prediction of survival; however, it remains uncertain whether LND independently improves survival in patients with UTUC.

Growth kinetics of renal masses: analysis of a prospective cohort of patients undergoing active surveillance.

BACKGROUND: Active surveillance (AS) represents a treatment option for renal masses in patients who are not surgical candidates either because of existing comorbidities or patient choice. Among renal masses undergoing AS, some grow rapidly and require treatment or progress to metastatic disease. Patient and tumour characteristics related to this more aggressive behaviour have been poorly studied. OBJECTIVE: To report the analysis of a multi-institutional cohort of patients undergoing AS for small renal masses. DESIGN, SETTING, AND PARTICIPANTS: This prospective study included 82 patients with 84 renal masses who underwent AS in three Canadian institutions between July 2001 and June 2009. INTERVENTION: All patients underwent AS for renal masses presumed to be renal cell carcinoma (RCC) as based on diagnostic imaging. MEASUREMENTS: Age, sex, symptoms at presentation, maximum diameter at diagnosis (cm), tumour location (central/peripheral), degree of endophytic component (1-100%), and tumour consistency (solid/cystic) were used to develop a predictive model of the tumour growth rate using binary recursive partitioning analysis with a repeated measures outcome. RESULTS AND LIMITATIONS: With a median follow-up of 36 mo (range: 6-96), the mean annual renal mass growth rate for the entire cohort was 0.25 cm/yr (standard deviation [SD]: 0.49 cm/yr). Only one patient (1.2%) developed metastatic RCC. Amongst all variables, maximum diameter at diagnosis was the only predictor of tumour growth rate, and two distinct growth rates were identified. Masses that are ≥2.45 cm in largest diameter at diagnosis grow faster than smaller masses. This series was limited by its moderate sample size, although it is the largest published prospective series to date. CONCLUSIONS: We confirm that most renal masses grow slowly and carry a low metastatic potential. Tumour size is a predictor of tumour growth rate, with renal masses <2.45 cm growing more slowly than masses >2.45 cm.

High-frequency percussive ventilation and low tidal volume ventilation in burns: a randomized controlled trial.

OBJECTIVES: In select burn intensive care units, high-frequency percussive ventilation is preferentially used to provide mechanical ventilation in support of patients with acute lung injury, acute respiratory distress syndrome, and inhalation injury. However, we found an absence of prospective studies comparing high-frequency percussive ventilation with contemporary low-tidal volume ventilation strategies. The purpose of this study was to prospectively compare the two ventilator modalities in a burn intensive care unit setting. DESIGN: Single-center, prospective, randomized, controlled clinical trial, comparing high-frequency percussive ventilation with low-tidal volume ventilation in patients admitted to our burn intensive care unit with respiratory failure. SETTING: A 16-bed burn intensive care unit at a tertiary military teaching hospital. PATIENTS: Adult patients ≥ 18 yrs of age requiring prolonged (> 24 hrs) mechanical ventilation were admitted to the burn intensive care unit. The study was conducted over a 3-yr period between April 2006 and May 2009. This trial was registered with ClinicalTrials.gov as NCT00351741. INTERVENTIONS: Subjects were randomly assigned to receive mechanical ventilation through a high-frequency percussive ventilation-based strategy (n = 31) or a low-tidal volume ventilation-based strategy (n = 31). MEASUREMENTS AND MAIN RESULTS: At baseline, both the high-frequency percussive ventilation group and the low-tidal volume ventilation group had similar demographics to include median age (interquartile range) (28 yrs [23-45] vs. 33 yrs [24-46], p = nonsignificant), percentage of total body surface area burn (34 [20-52] vs. 34 [23-50], p = nonsignificant), and clinical diagnosis of inhalation injury (39% vs. 35%, p = nonsignificant). The primary outcome was ventilator-free days in the first 28 days after randomization. Intent-to-treat analysis revealed no significant difference between the high-frequency percussive ventilation and the low-tidal volume ventilation groups in mean (± sd) ventilator-free days (12 ± 9 vs. 11 ± 9, p = nonsignificant). No significant difference was detected between groups for any of the secondary outcome measures to include mortality except the need for "rescue" mode application (p = .02). Nine (29%) in the low-tidal volume ventilation arm did not meet predetermined oxygenation or ventilation goals and required transition to a rescue mode. By contrast, two in the high-frequency percussive ventilation arm (6%) required rescue. CONCLUSIONS: A high-frequency percussive ventilation-based strategy resulted in similar clinical outcomes when compared with a low-tidal volume ventilation-based strategy in burn patients with respiratory failure. However, the low-tidal volume ventilation strategy failed to achieve ventilation and oxygenation goals in a higher percentage necessitating rescue ventilation.

Multi-drug resistant E.coli urosepsis in physicians following transrectal ultrasound guided prostate biopsies--three cases including one death.

Three male physicians underwent transrectal ultrasound guided prostate biopsies for elevated prostate-specific antigen levels or irregular digital rectal exam findings. All three of these patients developed urosepsis secondary to multi-drug resistant organisms despite antibiotic prophylaxis. There are increasing reports of infectious complications following prostate biopsy caused by multi-drug resistant organisms. These cases highlight the potentially lethal risks to healthcare workers who are more likely to harbor multi-drug resistant organisms than the general population. Further research into preoperative assessment and appropriate antibiotic prophylaxis in all potentially high risk patients is warranted.

The effects and expense of augmenting usual cancer clinic care with telephone problem-solving counseling.

This study was done to assess the effectiveness and efficiency of individualized, problem-solving counseling provided by baccalaureate nurses over the telephone to prevent the onset of depression in persons with breast, lung, or prostate cancer. Of 175 persons randomized, 149 completed the 8-month follow-up. The primary outcome measures were changes in the Jalowiec Coping Scale, the Centre for Epidemiologic Studies in Depression Scale, and the Derogotis Psychosocial Adjustment to Illness Scale. In addition, expenditures for people's use of all health and social services were computed at baseline and follow-up. Telephone counseling improved the use of more favorable coping behaviors, prevented a clinically important but not statistically significant decline into depression, and poor psychosocial adjustment in a group of people with mixed cancer. These results were associated with a greater total per person per annum expenditure for use of all other health and social services in the community compared with the control group. In a situation of limited resources and a service producing more effect for more costs, one needs either to examine what services to forgo to offer this service or to carefully target the new service to those most likely to benefit.

Incomplete and inconsistent information provided to men making decisions for treatment of early-stage prostate cancer.

OBJECTIVES: To determine whether there is a gap between what patients know about early-stage prostate cancer and what they need to know to make treatment decisions, and whether the information patients receive varies depending on their treating physician. METHODS: Needs assessment was performed using a questionnaire consisting of 41 statements about early-stage prostate cancer. Statements were divided into six thematic subsets. Participants used a 5-point Likert scale to rate statements in terms of knowledge of the information and importance to a treatment decision. Information gaps were defined as significant difference between the importance and knowledge of an item. Descriptive statistics were used to describe demographic subscale scores. The information gap was analyzed by a paired t test for each thematic subset. One-way analyses of variance were used to detect any differences on the basis of treating physician. RESULTS: Questionnaires were distributed to 270 men (135 treated by radical prostatectomy, 135 by external beam radiotherapy). The return rate was 51% (138 questionnaires). A statistically significant information gap was found among all six thematic subsets, with five of the six P values less than 0.0001. Statistically significant variation was observed in the amount of information patients received from their treating physicians among four of the thematic subsets. CONCLUSIONS: There is an information gap between what early-stage prostate cancer patients need to know and the information they receive. Additionally there is a difference in the amount of information provided by different physicians.

Primary malignant melanoma of the prostate: case report and review of the literature.

Primary malignant melanoma of the prostate is very rare. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found incidentally following transurethral resection of the prostate (TURP).

Gendered and cultured relations: exploring African Nova Scotians' perceptions and experiences of breast and prostate cancer.

Although breast and prostate cancer are those most frequently diagnosed in Canada, information about the ways in which gender, class, race, culture, and other social determinants impact the experience of African Canadians living with cancer is lacking. This study began to address this gap by exploring cultured and gendered dimensions of African Nova Scotians' experiences of these two cancers. Using a participatory action research approach, data were collected in two phases of focus group discussions in five African Nova Scotian communities from a total of 57 people, including those with breast or prostate cancer and their families and associates. Findings provide insight into how gender and meanings of masculinity and femininity in the African Nova Scotian community unavoidably interact with other social structures such as race and class to affect women and men's perceptions and experiences of these two cancers. These insights point to the need for culturally appropriate and meaningful health interventions. As a prerequisite, health care professionals need to have an understanding of the overlapping and contextualized nature of gender, class, and race and be willing and able to work in partnership with African Nova Scotian communities to identify and develop strategies that reflect the realities of peoples' lives.

Microsatellite instability in multifocal urothelial carcinoma and effect on BAX and AXIN2.

OBJECTIVES: Urothelial carcinomas have a synchronous or metachronous multifocal pattern of occurrence, questioning their clonal origin. Genetic alterations such as microsatellite instability (MSI) affect various tumors including urothelial cancers. These alterations can affect repeat sequences and cause mutations in coding regions of genes involved in transformation, tumor suppression and apoptosis. Recently, the eight-guanine (G8) and the seven-guanine (G7) repeat sequences of the BAX and AXIN2 genes respectively, were shown altered in different cancers. Since BAX is involved in apoptosis while the AXIN2 is involved in beta-catenin metabolism, a protein involved in cell adhesion and DNA transcription, and due to the multifocal nature of urothelial cancer, we investigated these two genes for alterations in repeat sequences in patients with this cancer. PATIENTS AND METHODS: The eight microsatellites BAT25, BAT26, D2S123, D3S1029, D5S346, D17S588, D17S261, MYCL1 were used to screen 25 tumors from seven patients with eight upper and 17 lower urinary tract carcinomas and compare them to DNA from normal tissue. Regions spanning the G8 and G7 repeat sequences of BAX and AXIN2 were sequenced for mutations including expansion and deletion abnormalities. RESULTS: Six microsatellites were seen altered in one patient with kidney and bladder cancer affecting both tissues when compared to normal DNA albeit not similarly except for MYCL1. There was no change in the BAX G8 or AXIN2 G7 microsatellites. There was no MSI seen in any of the remaining six patients. CONCLUSION: MSI occurs in urothelial cancer, but was not seen to affect the BAX G8 or AXIN2 G7 repeats in this study. However, to determine if MSI affects these genes in these tumors will require a larger study. Moreover, our results suggest that these tumors may have a monoclonal origin with further genetic changes resulting in oligoclonality, or could suggest a similar initiating event leading to a similar initial genetic alteration at different sites with subsequent varying events due to a genetically unstable malignant phenotype.

Preperitoneal mesh-plug herniorraphy during radical retropubic prostatectomy.

BACKGROUND: The treatment of localized prostate cancer has increased over the past decade in large part due to enhanced screening efforts with prostate specific antigen (PSA) and has resulted in a dramatic increase in the number of radical retropubic prostatectomies being performed in recent years. It is estimated that between 5% and 10% of men who are candidates for radical surgical treatment for localized prostate cancer will have concomitant inguinal hernia. Given the well described complications of untreated inguinal hernias we propose that simultaneous repair be undertaken along with radical retropubic prostatectomy for preoperatively defined hernias and those incidentally discovered at the time of surgery. MATERIAL AND METHODS: We concomitantly performed a novel inguinal hernia repair using a Marlex mesh plug in 15 patients who presented to our center for radical prostatectomy. RESULTS: There were no intra or post operative complications related to the repair. At a median follow up time of 18 months there were no developed recurrences or post operative orchalgia. CONCLUSION: Preperitoneal mesh-plug herniorraphy is a safe and effective technique used to repair inguinal hernias that present concomitantly with prostate cancer in patients undergoing radical retropubic prostatectomy.

Palliative Subcutaneous Tunneled Nephrostomy Tube (PSTN): a simple and effective technique for management of malignant extrinsic ureteral obstruction.

The establishment and maintenance of effective urinary tract drainage for patients with malignant extrinsic ureteric obstruction is a formidable challenge for the urologist. We have utilized an alternative method of urinary diversion, called Palliative Subcutaneous Tunneled Nephrostomy Tubes (PSTN), for long term urinary tract drainage when intracoropreal stenting has failed or is not tolerated. PSTN provides a simple and effective method of external urinary diversion and preservation of renal function. This technique should be an option in the armamentarium of urologists for management of malignant ureteral obstruction.