Revascularized Pyelo-Uretero-Cystoplasty in Patients with Chronic Bladder Outlet Obstruction Due to Ectopic Ureterocele: A Safe Surgical Technique with Superior Continence Outcomes

Purpose To present the outcomes of revascularized pyeloureterocystoplasty with ureterocele unroofing in end stage bladder patients with duplex system and ureterocele. Methods Thirteen patients with obstruction of intrauterine outlet from an ectopic obstructive ureterocele were included. Fourteen units of duplex systems underwent upper pole partial nephrectomy in conjunction with augmentation revascularized pyeloureterocystoplaty and ureterocele unroofing. The anterior and lateral walls of the ureterocele were excised before cystoplasty, and the resultant edges of the posterior wall were sutured to the bladder epithelium. Anastomosis of the upper pole vein and artery to the inferior iliac artery and the common iliac vein was performed. Detubularization of the whole ureter was performed with exception of the intramural ureteric part that kept tubularized for ‘jet/turbulent’ occurrence. Five patients (control group) underwent pyeloureterocystoplasty without revascularization. Patients underwent several evaluations in long-term follow-up. Results Patients were all dry by day and night in our long-term follow-up. Urinary incontinence improved in patients with no need for re-augmentation technique. Vesicoureteral reflux subsided in all patients postoperatively except one, who was asymptomatic. After five years, median bladder capacity rose from 128.5 ml to 395 ml and bladder compliance showed significant improvement from 15 ml/cm H2O to 29 ml/cm H2O, in experimental group and remained stable for 24–36 months. Median bladder capacity did not rise significantly in control group. Conclusion Pyeloureterocystoplasty is an efficient choice in this type of patients, which may prevent the recurrence of hypocompliant bladders and prevent ischemia and subsequent fibrosis

Bladder Rupture as a Complication of Circumcision following Total Subcoronal Urethral Ligation

Circumcision is one of the most commonly performed procedures and generally is considered a safe and minor surgery. However, serious and catastrophic complications may sometime occur if adequate attention is not paid to all aspects of this procedure. Bleeding is the most common early complication of circumcision and sometimes is controlled by applying sutures. We hereby report a case of urethral obstruction after deep suturing of the bleeding site performed at a district center that led to bladder rupture as an exceedingly rare complication following circumcision

The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia

Abstract The immune responses to cancer cells involve both innate and acquired immune cells. In the meantime, the most attention has been drawn to the adaptive immune cells, especially T cells, while, it is now well known that the innate immune cells, especially natural killer (NK) cells, play a vital role in defending against malignancies. While the immune cells are trying to eliminate malignant cells, cancer cells try to prevent the function of these cells and suppress immune responses. The suppression of NK cells in various cancers can lead to the induction of an exhausted phenotype in NK cells, which will impair their function. Recent studies have shown that the occurrence of this phenotype in various types of leukemic malignancies can affect the prognosis of the disease, and targeting these cells may be considered a new immunotherapy method in the treatment of leukemia. Therefore, a detailed study of exhausted NK cells in leukemic diseases can help both to understand the mechanisms of leukemia progression and to design new treatment methods by creating a deeper understanding of these cells. Here, we will comprehensively review the immunobiology of exhausted NK cells and their role in various leukemic malignancies. Video Abstrac

Dual Blockade of PD-1 and LAG3 Immune Checkpoints Increases Dendritic Cell Vaccine Mediated T Cell Responses in Breast Cancer Model

Purpose Increasing the efficiency of unsuccessful immunotherapy methods is one of the most important research fields. Therefore, the use of combination therapy is considered as one of the ways to increase the effectiveness of the dendritic cell (DC) vaccine. In this study, the inhibition of immune checkpoint receptors such as LAG3 and PD-1 on T cells was investigated to increase the efficiency of T cells in response to the DC vaccine. Methods We used trimethyl chitosan-dextran sulfate-lactate (TMC-DS-L) nanoparticles (NPs) loaded with siRNA molecules to quench the PD-1 and LAG3 checkpoints’ expression. Results Appropriate physicochemical characteristics of the generated NPs led to efficient inhibition of LAG3 and PD-1 on T cells, which was associated with increased survival and activity of T cells, ex vivo. Also, treating mice with established breast tumors (4T1) using NPs loaded with siRNA molecules in combination with DC vaccine pulsed with tumor lysate significantly inhibited tumor growth and increased survival in mice. These ameliorative effects were associated with increased anti-tumor T cell responses and downregulation of immunosuppressive cells in the tumor microenvironment and spleen. Conclusion These findings strongly suggest that TMC-DS-L NPs loaded with siRNA could act as a novel tool in inhibiting the expression of immune checkpoints in the tumor microenvironment. Also, combination therapy based on inhibition of PD-1 and LAG3 in combination with DC vaccine is an effective method in treating cancer that needs to be further studied