The Current Use of Stem Cells in Bladder Tissue Regeneration and Bioengineering.

Many pathological processes including neurogenic bladder and malignancy necessitate bladder reconstruction, which is currently performed using intestinal tissue. The use of intestinal tissue, however, subjects patients to metabolic abnormalities, bladder stones, and other long-term sequelae, raising the need for a source of safe and reliable bladder tissue. Advancements in stem cell biology have catapulted stem cells to the center of many current tissue regeneration and bioengineering strategies. This review presents the recent advancements in the use of stem cells in bladder tissue bioengineering

Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma.

The clinical deployment of immune checkpoint inhibitors (ICIs) has created a tandem drive for the identification of biomarkers linked to benefit. Comprehensive genomic profiling was performed to evaluate the frequency of genomic biomarkers of ICI response in 755 patients with advanced hepatocellular carcinoma (HCC). Median age was 62 years' old, 73% were male, 46% had extrahepatic disease, 107 had documented hepatitis C, 96 had hepatitis B and 4 patients were coinfected. Median tumor mutation burden (TMB) was 4 mutations/Mb and only 6 tumors (0.8%) were TMB-high. Out of 542 cases assessed for microsatellite instability (MSI), one (0.2%) was MSI-high and TMB-high. Twenty-seven (4%) patients had POLE/D alterations. One patient had a pathogenic POLE R762W mutation but TMB was 4 mutations/Mb. Forty percent had DNA damage response gene alterations. In a small case series (N=17) exploring the relationship between biomarkers and ICI response, one patient (TMB 15 mutations/Mb, MSI-low) had a sustained complete response to nivolumab lasting > 2 years. Otherwise there were no significant genomic or TMB differences between responders, progressors, and those with stable disease. Overall, markers of genomic instability were infrequent in this cohort. Larger clinically annotated datasets are needed to explore genomic and non-genomic determinants of ICI response in HCC

Body Composition, Symptoms, and Survival in Advanced Cancer Patients Referred to a Phase I Service

Background: Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown. Methods: We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)$25 kg/m 2 was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria. Results: Most patients were overweight (n = 65, 63$25 kg/m 2. Sarcopenic patients were older and less frequently African-American. Symptom burden did not differ among patients classified according to BMI and presence of sarcopenia. Median (95% confidence interval) survival (days) varied according to body composition: 215 (71–358) (BMI,25 kg/m 2; sarcopenic), 271 (99–443) (BMI,25 kg/m 2; non-sarcopenic), 484 (286–681) (BMI$25 kg/m 2; sarcopenic); 501 d (309–693) (BMI$25 kg/m 2; non-sarcopenic). Higher muscle index and gastrointestinal cancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index. Conclusions: Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI$25 kg/m 2, independent o

A New Appendicostomy Technique to Prevent Stomal Stenosis.

PURPOSE:Stomal stenosis has been reported to occur in 12% to 45% of patients following Malone antegrade continence enema and Mitrofanoff appendicostomy. The standard stoma technique entails excision of the distal appendix. We evaluated a novel technique with preservation of the appendiceal tip and vessels, and opening the lumen in a more proximal and vascular area to determine whether the incidence of stenosis would be decreased. MATERIALS AND METHODS:Medical records of patients who underwent appendicostomy for Malone antegrade continence enema or urinary diversion were retrospectively evaluated. We included cases with a minimum of 1 year of followup and those in which the distal portion of a complete appendix was oriented for use as the stomal end in the umbilicus. Variables such as age, gender, body mass index, antegrade continence enema or urinary diversion, open or laparoscopic approach, cecal and appendiceal adhesions, retrocecal position, cecal imbrication, technique and stenosis were recorded. Cox proportional hazards analyses were performed to determine association of covariates. RESULTS:A total of 123 patients met inclusion criteria. The incidence of stenosis following standard stoma technique was 13% (12 of 93 patients) with a median followup of 9.4 years. Of these cases 75% occurred within 1 year of surgery. Stomal stenosis did not occur after the new stoma technique in 30 patients with a median followup of 3.3 years. Only technique cohort (standard vs new) was associated with stenosis (p=0.04). CONCLUSIONS:Stomal stenosis of appendicostomy may be lessened by preservation of the distal appendiceal vasculature and tip, and opening the lumen in a more proximal location

No more shoulders: Technical modification of Byars' flaps

The repair of midshaft or more proximal hypospadias generally leads to a deficiency of ventral penile skin. Transposition of dorsal/lateral skin flaps may lead to redundant skin folds or shoulders. In most cases, redundant skin can be avoided by appropriate tailoring and positioning of the flaps. We describe a simple method to correct these folds when they are unavoidable

Production of urothelium from pluripotent stem cells for regenerative applications.

As bladder reconstruction strategies evolve, a feasible and safe source of transplantable urothelium becomes a major consideration for patients with advanced bladder disease, particularly cancer. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are attractive candidates from which to derive urothelium as they renew and proliferate indefinitely in vitro and fulfill the non-autologous and/or non-urologic criteria, respectively, that is required for many patients. This review presents the latest advancements in differentiating urothelium from pluripotent stem cells in vitro in the context of current bladder tissue engineering strategies

Adolescent varicocele: A large multicenter analysis of complications and recurrence in academic programs.

ObjectiveAfter varicocelectomy a wide range of recurrence rates have been reported from 0 to 18%, and rates of post-operative hydrocele formation between 0 and 29%. Controversy exists as to the appropriate approach for varicocele treatment, whether open, laparoscopic, or percutaneous embolization (PE) is best for young men. The literature on treatment of adolescent varicocele is limited to high-volume single surgeon, single institution, or small multi-institution series. Our goal was to evaluate the retreatment and complication rates from numerous institutions to determine more generalizable results.Study designThe Faculty Practice Solutions Center database was queried to identify males under age 19 years with a diagnosis and/or treatment of varicocele between January 2009 and December 2012. Patients were followed until December 2013 (1-5 years follow-up) to determine if they had occurrence of outcome variables: retreatment, diagnosis, or treatment of hydrocele. Associations of the variables age, race, insurance type, geographical region, surgeon-volume, and surgical approach, with outcome variables were analyzed using a mixed-effects Cox proportional hazard model.ResultsOf 6,729 patients with a diagnosis of varicocele, 1,036 underwent open (405), laparoscopic (530), or percutaneous embolization (PE) (101) treatment by 213 physicians. Retreatment rates after open, laparoscopic, and PE treatments were 1.5%, 3.4% and 9.9%, respectively. Race, region, insurance type, and age were not independently associated with outcomes. The incidence of hydrocele after open, laparoscopic, and PE treatments was 4.9%, 8.1%, and 5%, respectively. No approach was independently associated with diagnosis or treatment of hydrocele. Young age was associated with a significantly higher rate of hydrocele formation. For each year of age, there was a 14% decreased rate of hydrocele formation.DiscussionAlthough this series contains the largest cohort of patients, physicians, and institutions, we were limited by the inability to determine actual recurrence rates. Only patients receiving retreatment at the same institution within the 1-5 year follow-up period were captured. As such, the true rate of varicocele recurrence may be higher. The retreatment rate is influenced by the physician's threshold to retreat and the patient's desire to undergo another procedure. Despite its limitations, this is the first study to compare open, laparoscopic, and percutaneous approaches to varicocele treatment.ConclusionsPercutaneous embolization has a significantly higher retreatment rate compared with either open or laparoscopic varicocelectomy. Retreatment and hydrocele formation after open and laparoscopic approaches were not significantly different. This supports a surgeon and family choosing an approach based on patient characteristics and surgeon preference