Single Cell Mass Spectrometry Quantification of Anticancer Drugs: Proof of Concept in Cancer Patients.

In clinical cancer medicine, the current inability to quantify intracellular chemotherapy drug concentrations in individual human cells limits the personalization and overall effectiveness of drug administration. New bioanalytical methods capable of real-time measurement of drug levels in live single cancer cells would allow for more adaptive and personalized administration of chemotherapy drugs, potentially leading to better clinical outcomes with fewer side effects. In this study, we report the development of a new quantitative single cell mass spectrometry (qSCMS) method capable of providing absolute drug amounts and concentrations in single cancer cells. Using this qSCMS system, quantitative analysis of the intracellular drug gemcitabine present in individual bladder cancer cells is reported, including in bladder cancer cells isolated from patients undergoing standard-of-care gemcitabine chemotherapy. The development of single cell pharmacology bioanalytical methods can potentially lead to more effective and safely administered drug medications in patients, especially in the treatment of cancer.

Perineal schwannoma: A case report with novel genitourinary association and histopathology.

We describe a 39-year-old male patient who presented with a large perineal mass found to represent an entity rarely seen involving the genitourinary tract, a perineal schwannoma. We also provide a discussion regarding the common presentation, diagnostic approaches and treatment options for patients who present with this rare entity.

Reported rates of clostridium difficile following radical cystectomy in national datasets compared to individual institutions.

BACKGROUND: Clostridium difficile infection (CDI) is an important cause of hospital acquired morbidity with implications for quality of care. Radical cystectomy is a surgical procedure associated with high rates of morbidity one of which is a high rate of CDI. The rate of CDI among patients undergoing radical cystectomy may be estimated based on the reports from single institutions or by querying national databases. This study aims to compare rates of CDI reported in single institution series with rates obtained from national datasets. METHODS: A search was conducted on PubMed and Google Scholar using the terms "cystectomy+difficile" and "cystectomy+complication." Three hundred fifty articles were screened and 46 met criteria for inclusion based on the presence of specific rates of C. difficile following radical cystectomy. In the case of articles reporting on the same database, only the article with a larger sample size was included in the pooled analysis. One study reviewing a single institution was excluded from pooled analysis because it did not relate the rate of CDI specifically with cystectomy. Multi-institutional studies were not included in pooled analysis. RESULTS: After exclusion of repeated data and multi-institutional studies, the pooled analysis consisted of 39 studies. Thirty five articles reported rates of CDI in single institutions and 4 articles reported rates found in national databases. Studies focusing on a single institution reported an average 5.02% (standard deviation = 4.88) incidence of CDI, compared to an average of 1.92% (standard deviation = 0.22) in databases. The rate of CDI found by totaling patients and incidence of infection found that databases show a rate of 1.95%, while institutions show a rate of 4.11% (P < 0.0000001). CONCLUSION: The rate of CDI following radical cystectomy may be underestimated in national databases. This has implications for the development of health policy and quality measures based on the rate of CDI.

Clostridium difficile Infection in Contemporary Urologic Practice.

Clostridium difficile infection (CDI) is a high-impact hospital-acquired condition and a chief driver of excess morbidity, mortality, and treatment cost. The diagnosis, treatment, and prevention of CDI are key components of any hospital-based practice. Urologists see a small percentage of all patients with CDI, but traditionally utilize antibiotic agents that put patients at risk of CDI. Urologic procedures making use of bowel have a significantly higher rate of CDI than other procedures. This review addresses concepts that practicing urologists should be aware of and should be able to put into practice to diagnose, treat, and prevent CDI.

Percutaneous Stone Removal in an Adult with a Continent Cutaneous Reservoir: Case Report and Review of the Literature.

Stone formation is a known long-term complications of continent urinary reservoirs. We present a rare case of a large stone in a continent cutaneous reservoir in a 56-year-old male managed with percutaneous cystolithotomy. The patient presented with recurrent urinary tract infections and stomal incontinence. CT revealed an 8-cm stone occupying the entire lumen of his reservoir. Rather than removing this large stone through an open approach, the pouch was accessed percutaneously and lithotripsy was performed. In this report, we demonstrate our operative technique and that percutaneous cystolithalopaxy may be a safe and effective alternative for the management of large stones within continent cutaneous reservoirs.

Effect of alvimopan on return of bowel function after robot-assisted radical cystectomy.

INTRODUCTION: Alvimopan has been shown to improve time to return of bowel function in patients undergoing bowel resection. The objective of this study is to determine if alvimopan has similar benefits for patients undergoing robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: All RARC cases were reviewed from January 2008 to March 2012. All patients during this time were administered alvimopan unless they had been receiving narcotics preoperatively. Patients receiving alvimopan received a preoperative dose of 12 mg perorally and then were dosed twice daily for 7 days or until first bowel movement. Clinicopathologic outcomes were summarized and compared, and functional outcomes of treated patients were compared with outcomes of untreated patients. RESULTS: One hundred seventeen RARCs meeting study criteria were performed. All urinary diversions used an extracorporeal approach. Urinary diversions consisted of 50 Studer neobladders, 22 Indiana pouches, and 45 ileal conduits. Fifty-four patients received alvimopan, and 63 did not. The median time to first bowel movement was 5 days in the alvimopan group and 6 days in the untreated group (P=.03). Median time to solid diet was 6 days in the treated group and 7 days in the untreated group (P=.03). There was a trend toward fewer hospital days in the alvimopan group (alvimopan, 8 days; untreated, 9 days; P=.1). CONCLUSIONS: Alvimopan administration appears to reduce the time to return of bowel function and initiation of diet following RARC. This was a trend toward shorter hospitalization in the alvimopan group. Alvimopan should be considered in ongoing research into protocols to aid in shorter convalescence following RARC.

Suppression and activation of the malignant phenotype by extracellular matrix in xenograft models of bladder cancer: a model for tumor cell "dormancy".

A major problem in cancer research is the lack of a tractable model for delayed metastasis. Herein we show that cancer cells suppressed by SISgel, a gel-forming normal ECM material derived from Small Intestine Submucosa (SIS), in flank xenografts show properties of suppression and re-activation that are very similar to normal delayed metastasis and suggest these suppressed cells can serve as a novel model for developing therapeutics to target micrometastases or suppressed cancer cells. Co-injection with SISgel suppressed the malignant phenotype of highly invasive J82 bladder cancer cells and highly metastatic JB-V bladder cancer cells in nude mouse flank xenografts. Cells could remain viable up to 120 days without forming tumors and appeared much more highly differentiated and less atypical than tumors from cells co-injected with Matrigel. In 40% of SISgel xenografts, growth resumed in the malignant phenotype after a period of suppression or dormancy for at least 30 days and was more likely with implantation of 3 million or more cells. Ordinary Type I collagen did not suppress malignant growth, and tumors developed about as well with collagen as with Matrigel. A clear signal in gene expression over different cell lines was not seen by transcriptome microarray analysis, but in contrast, Reverse Phase Protein Analysis of 250 proteins across 4 cell lines identified Integrin Linked Kinase (ILK) signaling that was functionally confirmed by an ILK inhibitor. We suggest that cancer cells suppressed on SISgel could serve as a model for dormancy and re-awakening to allow for the identification of therapeutic targets for treating micrometastases.

Advanced penile cancer.

Penile cancer is an uncommon disease in the industrialized world that most frequently presents at low stage and is cured with treatment of local and regional surgery. In cases of advanced cancer, the use of more aggressive surgical techniques and the addition of adjuvant therapy may be warranted. So far, few agents have been found that improve survival with metastatic disease and thus aggressive primary treatment is required. This review discusses diagnosis, staging, and therapy for high risk penile cancer.

Multiple endocrine neoplasia 2a presenting with pheochromocytoma and pituitary macroadenoma.

Multiple Endocrine Neoplasia type 2A (MEN-2a) is a rare disease associated with tumors of endocrine organs. Presentation most commonly is with medullary thyroid cancer and infrequently with other complaints. Pituitary adenoma has been seen coincidentally with this disease very rarely. Presented is a case of coincident MEN-2a with a symptomatic pituitary adenoma and an asymptomatic pheochromocytoma. A brief review is also provided.

Successful removal of a penile constriction ring in a 14-year-old male.

Penile strangulation is a rarely described medical emergency, especially in the adolescent population. This case demonstrates the successful removal of a constricting metal ring from the penis of a 14-year-old male with a diamond blade equipped orthopedic oscillating saw while under ketamine anesthesia in the emergency department.

Operative versus nonoperative management of ureteropelvic junction obstruction in children.

OBJECTIVES: To describe and validate our strategy for treating patients with ureteropelvic junction obstruction operatively or nonoperatively according to ultrasonography and nuclear renal scan findings. METHODS: A retrospective analysis of 243 patients from 1999 to 2006 with grade 3-4 hydronephrosis was performed. Depending on the grade of hydronephrosis with parenchymal thinning on ultrasonography and renal function on the nuclear renal scan, patients were treated with immediate pyeloplasty, pyeloplasty after a period of observation, or observation only. RESULTS: Of 243 patients, 116 were found to have UPJO as determined by a half-life >20 minutes. The mean follow-up was 24.0 months (range 3-69). Immediate pyeloplasty was performed in 32 children, and 84 were treated conservatively. Crossover from observation to surgery occurred in 47 children. In the immediate pyeloplasty group, the mean pre- and postoperative differential function was 30.4% and 38.8%, respectively (P < .0001). In the observation-only group (n = 37), the initial mean renal function was 41.4% and stayed stable throughout the follow-up period, at a mean of 43.2% (P = .2764). In the delayed pyeloplasty group (n = 47), the initial mean renal function was 35.9% and increased to a mean of 41.6% after intervention (P = .0003). The median improvement of hydronephrosis on ultrasonography for those who underwent immediate surgery from before to after the intervention was from grade 4 to grade 3 (P < .0001). For those not undergoing surgery, it improved from grade 4 to grade 2.25 (P = .0026) and for those who underwent delayed surgery, from grade 4 to 3 (P = .0003). CONCLUSIONS: According to our findings, the serial ultrasonography findings and initial renal function on nuclear renal scan are better indicators than the half-life alone for determining whether pyeloplasty is indicated.

Occurrence of urinary tract infection in children with significant upper urinary tract obstruction.

OBJECTIVES: Ureteropelvic junction obstruction and obstructive megaureter are common causes of upper urinary tract obstruction. Recent data have demonstrated that the rate of urinary tract infection (UTI) among children with upper tract obstruction not treated with prophylactic antibiotics is >36%. The aim of this study was to evaluate the occurrence of UTI in our patients with ureteropelvic junction obstruction and megaureter to better assess the role of prophylactic antibiotics. METHODS: A retrospective analysis was conducted. The inclusion criteria were grade 3 or 4 hydronephrosis secondary to obstructive megaureter or ureteropelvic junction obstruction in children not maintained on prophylactic antibiotics. UTI was defined as a culture-documented symptomatic infection. Fisher's exact tests were used to evaluate for an association between the occurrence of UTI with sex, level of obstruction, grade of hydronephrosis, and circumcision status. RESULTS: A total of 92 patients met the study criteria. The rate of UTI in all patients was 4.3% (95% confidence interval 0.2%-8.6%). No statistically significant difference in the infection rate was noted according to sex, obstruction level, hydronephrosis grade, or circumcision status. CONCLUSIONS: Our results have demonstrated a low occurrence of UTI in antenatally diagnosed patients not maintained on antibiotics. We have concluded that antibiotic prophylaxis is unlikely to benefit most children with grade 3 or 4 hydronephrosis secondary to upper tract obstruction.