Applicability of regenerative medicine and tissue engineering for the treatment of stress urinary incontinence in female patients.

Stress urinary incontinence (SUI) is an age health-related issue that generates interest due to its considerable public health burden and the controversies surrounding treatment. It is highly prevalent affecting 30-40% of all women during their lifetime. Midurethral slings are the standard of gold standard treatment for female patients with SUI. They have excellent short-term cure rates; however, their efficacy tends to decrease over time and patients often report urinary incontinence recurrence. This paper addresses the applicability of regenerative medicine and tissue engineering for the treatment of SUI in female patients. Cell-based treatment with periurethral injection of autologous adipose or muscle-derived stem cells have been used for SUI; however, the cure rates and SUI recurrence at 1 year were 40% and 70%, respectively. Novel minimally invasive approaches, such as low-intensity extracorporeal shock wave therapies have shown promising results in SUI animal models. In addition, local injection of growth factors, chemokines, and specific antibodies have shown histological evidence of neoangiogenesis, nerve, and sphincter regeneration in rodents and nonhuman primates with SUI. The use of bioactive factors and proteins secreted by cells, which is called secretomes, have been recognized as key regulators of various mechanisms, such as immunomodulation, angiogenesis, inflammation, apoptosis, and tissue repair. Emerging therapies aiming to replace or restore tissues and organ functionality may improve the long-term efficacy and in the near future may represent the standard of care for the treatment of SUI.

Evaluation of Clinical Use and Cost-Effectiveness of a Flexible Cystoscope System with a Disposable Sheath: A Randomized Clinical Trial.

INTRODUCTION: Flexible cystoscopy is routinely performed as an outpatient procedure. The use of disposable sheaths can increase cystoscope life span and reduce staff costs. The primary end point of this study was to evaluate procedure related discomfort and pain, physician maneuverability, residual bioburden and reprocessing time. The secondary end point was to analyze the cost-effectiveness of a flexible cystoscope with a disposable sheath compared to a standard flexible cystoscope. METHODS: This randomized clinical trial was performed with women older than 18 years, with intact cognition and 7 days antibiotic-free who were referred to outpatient clinic for cystoscopy. Patients underwent cystoscopy with a standard flexible cystoscope or flexible cystoscope with disposable sheath. Urinalysis and culture were performed before and 14 days after cystoscopy. Patients filled out a pain/discomfort visual analog scale. Physicians filled out a 5-point Likert scale for the elements of ease of insertion, manipulation, optical quality and overall use. Reprocessing time and costs were compared between both cystoscopes. RESULTS: A total of 60 patients were included in the study, comprised of 30 who underwent standard flexible cystoscopy and 30 who underwent flexible cystoscopy with a protective sheath. Patient discomfort/pain was equivalent in both groups. The Likert scores were similar except for ease of insertion, which was higher with protective sheaths (p <0.02). Protective sheaths were associated with lower reprocessing time and costs (p <0.001). CONCLUSIONS: The use of protective sheaths effectively reduced procedure and staff related costs without causing any additional patient discomfort or pain. The learning curve of the sheathed scope may explain the difference reported by physicians regarding the ease of insertion.

Nonhuman primate model of persistent erectile and urinary dysfunction following radical prostatectomy: Feasibility of minimally invasive therapy.

OBJECTIVE: Persistent urinary incontinence (UI) and/or erectile dysfunction (ED) occur in 30-50% of post-radical prostatectomy patients regardless of nerve sparing approaches. Identification of potential treatment options for these patients will require testing in an animal model that develops these chronic conditions. The objective was to characterize a nonhuman primate (NHP) model of persistent post-prostatectomy ED and UI and then test the feasibility of periurethral injection of the chemokine CXCL-12. METHODS: Ten adult male cynomolgus monkeys were used. Two were used for study of normal male nonhuman primate genitourinary anatomy. Five were used for measures of sexual behavior, peak intra-corporal pressure (ICP), abdominal leak point pressures (ALPP) 3 and 6-months post open radical prostatectomy (ORP). Three additional ORP animals received ultrasound-guided peri-urethral injection of chemokine CXCL12 6 weeks after ORP, and UI/ED evaluated for up to 3 months. RESULTS: The anatomy, innervation, and vascular supply to the prostate and surrounding tissues of these male NHPs are substantially similar to those of human beings. ORP resulted in complete removal of the prostate gland along with both neurovascular bundles and seminal vesicles while permitting stable restoration of vesico-urethral patency. ORP produced sustained (6 months) decreases in ALPP, ICP's, and sexual function. Transurethral injection of chemokine CXCL12 was feasible and had beneficial effects on erectile and urinary function. CONCLUSIONS: ORP in NHPs produced persistent erectile and urinary tract dysfunction. Periurethral injection of CXCL-12 was feasible and improved both urinary incontinence and erectile dysfunction and suggests that this model can be used to test new approaches for both conditions.

Midurethral Slings.

Urinary incontinence (UI) is a common symptom affecting almost one-third of adult women. UI can occur because of hypermobility or intrinsic sphincter deficiency of the urethra. Regardless its etiology, it is associated with poor quality of life and most of the incontinent women develop symptoms such as anxiety, depression, and social isolation over time. The synthetic midurethral sling (MUS) was first introduced in 1995 and quickly became the gold standard treatment for women with stress UI because of intrinsic sphincter deficiency and/or urethral hypermobility. This session addresses the indications, preoperative preparation, surgical steps, postoperative care, and complications related to synthetic MUSs. Owing to the exponential increase in the prevalence of mesh-related complications, we also developed a rational evidence-based algorithm that will help urologists to diagnose and manage this specific subset of patients.

Bladder and Ureteral Dysfunction Leading to Hydronephrosis and Hydroureteronephrosis in Adults.

Chronic non-stone-related hydronephrosis from supravesical or bladder dysfunction in adults is often detected incidentally. This study aims to review the literature regarding supravesical obstruction or bladder dysfunction leading to bilateral hydronephrosis in adults and to develop an algorithm to identify patients at risk of renal failure. Cross-sectional studies, retrospective and prospective cohorts, clinical trials, and systematic reviews from 1980 to 2017 were included. From 8115 articles screened, 39 met the inclusion criteria. Despite the lack of studies addressing this issue, this review brings up a rational evidence-based algorithm to diagnose and manage adults with bilateral hydronephrosis due to supravesical or bladder disease or dysfunction.

Vaginal Mesh Exposure Presentation, Evaluation, and Management.

INTRODUCTION: According to FDA, in 2010, approximately 300,000 women underwent surgical procedures in the USA to repair pelvic organ prolapse and approximately 260,000 underwent surgical procedures to repair stress urinary incontinence. From 560,000 surgeries, synthetic mesh was used in one out of three, and three out of four were performed transvaginally. The incorporation of mesh into pelvic organ prolapse repair has improved the long-term surgical anatomical outcomes and lower recurrence rates. However, vaginal mesh placement is associated with risks such as vaginal mesh erosion, exposure, and infection. OBJECTIVE: The main objectives of this study were to review the literature regarding vaginal mesh exposure and, based on the literature evidences, develop an algorithm to help urologists and gynecologists to promptly recognize the problem and treat it effectively with minimal additional morbidity. RESULTS: Diabetes mellitus, advanced age, smoking, concomitant hysterectomy, surgeon's experience, surgical technique, and proper training in pelvic organ reconstructive procedures have all been shown to be risk factors for vaginal mesh exposure. The clinical presentation of mesh exposure varies and the management depends upon the extent and location of exposure, associated patient bother, voiding complaints, and involvement of adjacent viscera if any. Once vaginal mesh exposure is diagnosed, it would be pragmatic to rule out simultaneous perforation/erosion into the bladder/urethra or bowel and associated collection if any. CONCLUSIONS: The exponential increase in the number of mesh-related complications is related mainly to a lack of surgeon's experience and proper training in reconstructive pelvic surgeries as well as availability of easy-to-handle kits. Despite improvements in short- and long-term outcomes since the introduction of mesh in pelvic surgeries, the incidence of post-operative complications remains elevated. We developed an algorithm to facilitate prompt recognition and treatment of vaginal mesh exposure aiming to help urologists and gynecologists to achieve better outcomes and success rates.

The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas.

OBJECTIVES: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.

Current achievements and future perspectives in whole-organ bioengineering.

Irreversible end-stage organ failure represents one of the leading causes of death, and organ transplantation is currently the only curative solution. Donor organ shortage and adverse effects of immunosuppressive regimens are the major limiting factors for this definitive practice. Recent developments in bioengineering and regenerative medicine could provide a solid base for the future creation of implantable, bioengineered organs. Whole-organ detergent-perfusion protocols permit clinicians to gently remove all the cells and at the same time preserve the natural three-dimensional framework of the native organ. Several decellularized organs, including liver, kidney, and pancreas, have been created as a platform for further successful seeding. These scaffolds are composed of organ-specific extracellular matrix that contains growth factors important for cellular growth and function. Macro- and microvascular tree is entirely maintained and can be incorporated in the recipient's vascular system after the implant. This review will emphasize recent achievements in the whole-organ scaffolds and at the same time underline complications that the scientific community has to resolve before reaching a functional bioengineered organ.

Prospect for kidney bioengineering: shortcomings of the status quo.

INTRODUCTION: Dialysis and renal transplantation are the only two therapeutic options offered to patients affected by end-stage kidney disease; however, neither treatment can be considered definitive. In fact, dialysis is able to replace only the filtration function of the kidney without substituting its endocrine and metabolic roles, and dramatically impacts on patient's quality of life. On the other hand, kidney transplantation is severely limited by the shortage of transplantable organs, the need for immunosuppressive therapies and a narrow half-life. Regenerative medicine approaches are promising tools aiming to improve this condition. AREAS COVERED: Cell therapies, bioartificial kidney, organ bioengineering, 3D printer and kidney-on-chip represent the most appealing areas of research for the treatment of end-stage kidney failure. The scope of this review is to summarize the state of the art, limits and directions of each branch. EXPERT OPINION: In the future, these emerging technologies could provide definitive, curative and theoretically infinite options for the treatment of end-stage kidney disease. Progress in stem cells-based therapies, decellularization techniques and the more recent scientific know-how for the use of the 3D printer and kidney-on-chip could lead to a perfect cellular-based therapy, the futuristic creation of a bioengineered kidney in the lab or to a valid bioartificial alternative.

Hand-assisted laparoscopic nephrectomy as a minimally invasive option in the treatment of large renal specimens

INTRODUCTION: We describe our experience with hand-assisted laparoscopy (HAL) as an option for the treatment of large renal specimens. MATERIALS AND METHODS: Between March 2000 and August 2004, 13 patients candidate to nephrectomies due to benign renal conditions with kidneys larger than 20 cm were included in a prospective protocol. Unilateral nephrectomy was performed in cases of hydronephrosis (6 patients) or giant pyonephrosis (4 patients). Bilateral nephrectomy was performed in 3 patients with adult polycystic kidney disease (APKD) with low back pain refractory to clinical treatment previous to kidney transplant. The technique included the introduction of 2 to 3 10 mm ports, manual incision to allow enough space for the surgeon's wrist without a commercial device to keep the pneumoperitoneum. The kidney was empty, preferably extracorporeally, enough to be removed through manual incision. We have assessed operative times, transfusions, complications, conversions, hospital stay and convalescence. RESULTS: The patients mean age (9 women and 4 men) was 58 years. Mean operating time was 120 n 10 min (hydronephrosis), 160 n 28 min (pyonephrosis) and 190 n 13 min (bilateral surgery for APKD). There was a need for a conversion in 1 case and another patient needed a transfusion due to a lesion in the renal vein; 2 patients had minor complications. CONCLUSION: HAL surgery is a minimally invasive alternative in the treatment of large renal specimens, with or without significant inflammation.

Laparoscopic surgery for treatment of incisional lumbar hernia.

OBJECTIVE: To present results obtained with laparoscopic correction of incisional lumbar hernia in patients with minimum follow-up of 1 year. MATERIALS AND METHODS: We prospectively studied 7 patients diagnosed with incisional lumbar hernia after physical examination and computerized tomography. We used laparoscopic transperitoneal access through 3 ports. One polypropylene mesh was introduced in the abdominal cavity and fixed by titanium clamps to the margins of the hernia ring following release of the peritoneum. RESULTS: All cases were successfully completed with no conversion required. Mean surgical time was 120 minutes and discharge from hospital occurred between the 1st and the 2nd postoperative days. There were no intraoperative complications or hernia recurrence in any case. Postoperatively, we had 2 minor complications: one case of seroma that resolved spontaneously after 60 days and one patient presenting lumbar pain that persisted until the 3rd postoperative month. The return to usual activities occurred on average 3 weeks following intervention. Of the 7 patients, 6 were satisfied with the esthetical and functional effect produced by the procedure. CONCLUSIONS: The surgical correction of incisional lumbar hernia by laparoscopic access is an excellent option for a minimally invasive treatment, with adequate long-term results.

Laparoscopic surgery for treatment of incisional lumbar hernia

OBJECTIVE: To present results obtained with laparoscopic correction of incisional lumbar hernia in patients with minimum follow-up of 1 year. MATERIALS AND METHODS: We prospectively studied 7 patients diagnosed with incisional lumbar hernia after physical examination and computerized tomography. We used laparoscopic transperitoneal access through 3 ports. One polypropylene mesh was introduced in the abdominal cavity and fixed by titanium clamps to the margins of the hernia ring following release of the peritoneum. RESULTS: All cases were successfully completed with no conversion required. Mean surgical time was 120 minutes and discharge from hospital occurred between the 1st and the 2nd postoperative days. There were no intraoperative complications or hernia recurrence in any case. Postoperatively, we had 2 minor complications: one case of seroma that resolved spontaneously after 60 days and one patient presenting lumbar pain that persisted until the 3rd postoperative month. The return to usual activities occurred on average 3 weeks following intervention. Of the 7 patients, 6 were satisfied with the esthetical and functional effect produced by the procedure. CONCLUSIONS: The surgical correction of incisional lumbar hernia by laparoscopic access is an excellent option for a minimally invasive treatment, with adequate long-term results.

Hand-assisted laparoscopic nephrectomy as a minimally invasive option in the treatment of large renal specimens.

INTRODUCTION: We describe our experience with hand-assisted laparoscopy (HAL) as an option for the treatment of large renal specimens. MATERIALS AND METHODS: Between March 2000 and August 2004, 13 patients candidate to nephrectomies due to benign renal conditions with kidneys larger than 20 cm were included in a prospective protocol. Unilateral nephrectomy was performed in cases of hydronephrosis (6 patients) or giant pyonephrosis (4 patients). Bilateral nephrectomy was performed in 3 patients with adult polycystic kidney disease (APKD) with low back pain refractory to clinical treatment previous to kidney transplant. The technique included the introduction of 2 to 3 10 mm ports, manual incision to allow enough space for the surgeon's wrist without a commercial device to keep the pneumoperitoneum. The kidney was empty, preferably extracorporeally, enough to be removed through manual incision. We have assessed operative times, transfusions, complications, conversions, hospital stay and convalescence. RESULTS: The patients mean age (9 women and 4 men) was 58 years. Mean operating time was 120 +/- 10 min (hydronephrosis), 160 +/- 28 min (pyonephrosis) and 190 +/- 13 min (bilateral surgery for APKD). There was a need for a conversion in 1 case and another patient needed a transfusion due to a lesion in the renal vein; 2 patients had minor complications. CONCLUSIONS: HAL surgery is a minimally invasive alternative in the treatment of large renal specimens, with or without significant inflammation.

Retroperitoneal lymphadenectomy by videolaparoscopic transperitoneal approach in patients with non-seminomatous testicular tumor.

OBJECTIVE: The present study aims to report the preliminary experience with videolaparoscopic retroperitoneal lymphadenectomy in the treatment of patients with non-seminomatous testicular tumor. MATERIALS AND METHODS: Seven surgeries were performed in order to access retroperitoneal lymph nodes in patients with non-seminomatous testicular cancer. We performed the videolaparoscopic retroperitoneal lymphadenectomy (LRL) technique in 5 patients with stage I disease and laparoscopic resection of residual mass (LRRM), following chemotherapy (ChT), in 2 patients with stage II disease. Initial approach was obtained through 4 trocars, using an incision in supra-umbilical midline when manual assistance was required. Surgical time was analyzed, as well as blood loss, need for analgesic drugs postoperatively, hospital stay, complications, need for blood transfusion, histopathological data and tumor control in a mean follow-up of 18 months. RESULTS: Mean surgical time was 200 to 260 minutes in LRL and LRRM groups respectively, mean blood loss was 300 mL for the LRL group and 400 mL for the LRRM group, without need for transfusions. There was a lesion in the vena cava in the LRL group, which was managed with manual assistance and one conversion in the LRRM group, due to a 10-cm tumor mass that was adhered to the aorta. Mean hospital stay was 3 days, excluding the converted case, and the use of analgesic drugs was needed until the second postoperative day. Of the stage I patients, 2 had active disease in retroperitoneum, and underwent adjuvant ChT. The 2 residual masses were teratomas. There was no recurrence during the follow-up period. CONCLUSIONS: Videolaparoscopic retroperitoneal lymphadenectomy is a procedure with high technical complexity and a higher potential for conversion when performed following chemotherapy.

Retroperitoneal lymphadenectomy by videolaparoscopic transperitoneal approach in patients with non-siinomatous testicular tumor

OBJECTIVE: The present study aims to report the preliminary experience with videolaparoscopic retroperitoneal lymphadenectomy in the treatment of patients with non-siinomatous testicular tumor. MATERIALS AND METHODS: Seven surgeries were performed in order to access retroperitoneal lymph nodes in patients with non-siinomatous testicular cancer. We performed the videolaparoscopic retroperitoneal lymphadenectomy (LRL) technique in 5 patients with stage I disease and laparoscopic resection of residual mass (LRRM), following chiotherapy (ChT), in 2 patients with stage II disease. Initial approach was obtained through 4 trocars, using an incision in supra-umbilical midline when manual assistance was required. Surgical time was analyzed, as well as blood loss, need for analgesic drugs postoperatively, hospital stay, complications, need for blood transfusion, histopathological data and tumor control in a mean follow-up of 18 months. RESULTS: Mean surgical time was 200 to 260 minutes in LRL and LRRM groups respectively, mean blood loss was 300 mL for the LRL group and 400 mL for the LRRM group, without need for transfusions. There was a lesion in the vena cava in the LRL group, which was managed with manual assistance and one conversion in the LRRM group, due to a 10-cm tumor mass that was adhered to the aorta. Mean hospital stay was 3 days, excluding the converted case, and the use of analgesic drugs was needed until the second postoperative day. Of the stage I patients, 2 had active disease in retroperitoneum, and underwent adjuvant ChT. The 2 residual masses were teratomas. There was no recurrence during the follow-up period. CONCLUSIONS: Videolaparoscopic retroperitoneal lymphadenectomy is a procedure with high technical complexity and a higher potential for conversion when performed following chiotherapy.