Transurethral resection of bladder tumour complicated by perforation requiring open surgical repair – clinical characteristics and oncological outcomes

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Evidence suggests that open repair of a bladder perforation during TURBT may increase the risk of pelvic or distant disease recurrence. The study demonstrates that while bladder violation during TURBT may carry a potential for considerable morbidity, it does not seem to substantially increase the risk of extravesical tumour seeding and disease recurrence.

OBJECTIVE

? To examine the clinical characteristics and long‐term outcomes of patients with bladder perforation requiring open surgical repair as a complication of transurethral resection of bladder tumour (TURBT).

PATIENT AND METHODS

? A search of our institutional database yielded 4144 patients who underwent TURBT from 1996 to 2008, of whom 15 (0.36%) required open surgical intervention to repair a large bladder perforation. ? In all cases, a filling cystogram was performed before laparotomy. Clinical, pathological and follow‐up data were reviewed, and the incidence and time of extravesical tumour recurrence were recorded.

RESULTS

? Median patient age was 77 years. Intraperitoneal perforation was diagnosed in 12 patients, generally involving the posterior wall. Concomitant bowel injury was identified in two patients and managed by primary repair. Two patients in whom the diagnosis and intervention were delayed died within 1 week of surgery. ? Metastatic progression was observed in two patients shortly after the perforation (median interval, 4.8 months), and local pelvic recurrence was noted in one of them. ? None of the patients with stage Ta tumours had evidence of extravesical progression. Actuarial estimates of disease‐free survival at 1, 3 and 5 years after the perforation were 83%, 71% and 41%, respectively.

CONCLUSIONS

? A significant bladder perforation during TURBT requiring open surgical repair is more likely to occur in elderly patients with large posterior wall tumours and heavily pretreated bladders. ? Despite its potential for considerable morbidity, this adverse event does not seem to substantially increase the risk of extravesical tumour seeding. Prompt diagnosis, immediate intervention and meticulous bladder and bowel inspection during laparotomy are imperative.     

Controlled release of BMP‐2 from a sintered polymer scaffold enhances bone repair in a mouse calvarial defect model

Sustained and controlled delivery of growth factors, such as bone morphogenetic protein 2 (BMP‐2), from polymer scaffolds has excellent potential for enhancing bone regeneration. The present study investigated the use of novel sintered polymer scaffolds prepared using temperature‐sensitive PLGA/PEG particles. Growth factors can be incorporated into these scaffolds by mixing the reconstituted growth factor with the particles prior to sintering. The ability of the PLGA/PEG scaffolds to deliver BMP‐2 in a controlled and sustained manner was assessed and the osteogenic potential of these scaffolds was determined in a mouse calvarial defect model. BMP‐2 was released from the scaffolds in vitro over 3 weeks. On average, ca. 70% of the BMP‐2 loaded into the scaffolds was released by the end of this time period. The released BMP‐2 was shown to be active and to induce osteogenesis when used in a cell culture assay. A substantial increase in new bone volume of 55% was observed in a mouse calvarial defect model for BMP‐2‐loaded PLGA/PEG scaffolds compared to empty defect controls. An increase in new bone volume of 31% was observed for PLGA/PEG scaffolds without BMP‐2, compared to empty defect controls. These results demonstrate the potential of novel PLGA/PEG scaffolds for sustained BMP‐2 delivery for bone‐regeneration applications. Copyright © 2012 John Wiley & Sons, Ltd.     

Enhancement of bone defect healing in old rats by TGF-beta and IGF-1

Bone defects are often created in order to repair bone pathologies. In the aging population, the healing of such defects is very limited. Bone healing in aging depends on the availability of various hormone and growth factors. The ability of growth factors to enhance bone formation in femoral defects in old rats was tested. Bone defects were induced in femurs of old rats. A single dose of transforming growth factor-beta (TGF-beta), IGF-1, TGF-beta+IGF-1 or saline was inserted in the defect and bones were tested after 2 and 4 weeks. Radiology revealed that mineralization appeared in the 2 weeks group in defects treated with TGF-beta and in defects treated with TGF-beta, TGF-beta+IGF-1 in the 4 weeks groups. Computerized tomography (CT) coronal and axial images revealed that 4 weeks after treatment with TGF-beta+IGF-1, a complete bone bridge was observed. Morphology revealed that these defects were filled with trabecular bone. A less pronounced bone healing was observed after TGF-beta or IGF-1, while control specimens revealed partial healing of the bone defect. Biomechanical tests indicated that treatment with TGF-beta, IGF-1 or TGF-beta+IGF-1 resulted in a significant increase of bone bending rigidity compared to control in the 4 weeks group and that TGF-beta+IGF-1 was the most inductive in this respect. The ability to induce bone healing in aging by TGF-beta+IGF-1 is of a great clinical importance for restoration of bone strength and biomechanical properties of bone defects in aging.     

42 kDa Protein as a Substrate for Protein Phosphatase (s) in Intact Human Blood Platelets

The level of phosphorylation of any cellular protein depends on the balance of the activities of protein kinases and protein phosphatases that act on the protein. In this study, we have characterized, in intact human blood platelets, the activity of protein phosphatase (s) that reverse the action of protein kinase C (PKC), using as a substrate, endogenous 42 kDa protein which has been previously phosphorylated by PKC. In this study 1,2-dihexanoyl-sn-glycerol (DHG) was used to stimulate PKC, diacylglycerol kinase inhibitor-R59022 was used to maintain the activity of PKC and staurosporine and okadaic acid were used to inhibit PKC and protein phosphatases respectively. Our observations indicate that: (1) protein phosphatase 1 (PP1) and/or protein phosphatase 2A (PP2A) are likely to be the enzymes that reverse the phosphorylation activity of PKC on the 42 kDa protein; (2) PP1 and/or PP2A dephosphorylate sites which have been previously phosphorylated by PKC; and (3) PP1 and/or PP2A dephosphorylate, on the 42 kDa protein, both serine and threonine residues, which have been previously phosphorylated by PKC.     

Protein Kinase C of Human Platelets: Resolution of Ca(2+)-dependent and Independent Forms by Measuring Endogenous Phosphorylation

This study explores a kinetic approach to distinguish Ca(2+)-dependent and independent forms of PKC activity in a cell-free system of human platelets. Incorporation of (32)P from [γ-(32)P] ATP into total proteins, in the presence or in the absence of histone IIIS, at various combinations of added lipids (diolein and phosphatidyl serine) and Ca(2+), fail to distinguish PKC from other kinases. Phosphorylation of the 40 kDa protein, a major and specific platelet PKC substrate resolved by SDS-PAGE, is completely dependent on the added lipids, allowing the determination of PKC and its two sub-forms: dependent and independent Ca(2+). The activities of these forms and their ratio are characteristics for an individual, while the inter-individual difference is much greater, with an overall average ratio of 2:1 (n = 9). The forms differ in sensitivity to staurosporine with IC(50) = 14.6 and 4.3 nM for the Ca(2+)-dependent and independent forms, respectively. Furthermore, cAMP at 1 μM inhibits selectively the Ca(2+)-dependent form by 45%. Okadaic acid, a potent inhibitor of protein phosphatase 1 and 2A, enhances at 1 μM the activity of the Ca(2+)-dependent form. It is concluded that the two PKC forms that are determined in the crude cell free system of human platelets by measuring the endogenous phosphorylation have distinct properties.