Laparoscopic nephrectomy for giant staghorn calculus with non-functioning kidneys: Is associated unsuspected urothelial carcinoma responsible for conversion? Report of 2 cases

BACKGROUND-: Neglected renal stones remain a major cause of morbidity in developing countries. They not only result in functional impairment of affected kidney, but also act as an important predisposing factor for development of urothelial neoplasms. It is not uncommon to miss an associated urothelial tumor in a patient of nephrolithiasis preoperatively. CASE PRESENTATION-: In last 3 years, we came across two patients with giant staghorn calculus and poorly functioning kidneys who underwent laparoscopic nephrectomy. In view of significant perirenal adhesions & loss of normal tissue planes both these patients were electively converted to open surgery. The pathological examination of specimen revealed an unsuspected urothelial carcinoma in both these patients. The summary of our cases and review of literature is presented. CONCLUSION-: It is important to keep a differential diagnosis of associated urothelial malignancy in mind in patient presenting with long standing renal calculi. The exact role of a computerized tomography and cytology in preoperative workup for detection of possible associated malignancy in such condition is yet to be defined. Similarly if laparoscopic dissection appears difficult during nephrectomy for a renal calculus with non-functional kidney, keeping a possibility of associated urothelial malignancy in mind it is advisable to dissect in a plane outside gerotas fascia as for radical nephrectomy

Organization of multiprotein complexes at cell–cell junctions

The formation of stable cell–cell contacts is required for the generation of barrier-forming sheets of epithelial and endothelial cells. During various physiological processes like tissue development, wound healing or tumorigenesis, cellular junctions are reorganized to allow the release or the incorporation of individual cells. Cell–cell contact formation is regulated by multiprotein complexes which are localized at specific structures along the lateral cell junctions like the tight junctions and adherens junctions and which are targeted to these site through their association with cell adhesion molecules. Recent evidence indicates that several major protein complexes exist which have distinct functions during junction formation. However, this evidence also indicates that their composition is dynamic and subject to changes depending on the state of junction maturation. Thus, cell–cell contact formation and integrity is regulated by a complex network of protein complexes. Imbalancing this network by oncogenic proteins or pathogens results in barrier breakdown and eventually in cancer. Here, I will review the molecular organization of the major multiprotein complexes at junctions of epithelial cells and discuss their function in cell–cell contact formation and maintenance

Surgical revision of dysfunctional filtration blebs with bleb preservation, sliding conjunctival flap and fibrin glue

Purpose The introduction of anti-metabolite regimens to glaucoma filtration surgery has improved post-operative intraocular pressure (IOP) control; however, it has also increased the frequency of dysfunctional blebs. In this study, we report a surgical technique for the repair of trabeculectomy blebs using bleb preservation, a sliding conjunctival flap, and fibrin glue.Methods This study is a retrospective, non-comparative, consecutive case series involving 10 eye samples collected from 10 patients (6 M: 4 F) with one or a combination of bleb overfiltration, dysesthesia, thinning, leak, or blebitis, in which a conjunctival flap was advanced over the failing bleb and secured in place using fibrin glue and sutures.Results All patient eyes had symptom resolution post-operatively. There were no bleb leaks or hypotonous eyes after an average follow-up of 15.2 months (range: 6-31 months). Three patients required needling augmented with 5-fluorouracil needling to maintain IOP control. IOP decreased from a mean of 13.61.8 mm Hg (with a mean of 0.7 glaucoma medications) pre-operatively to 11.70.9 mm Hg (with a mean of 0.9 glaucoma medications).Conclusion Conjunctival flap advancement with bleb preservation and adjunctive fibrin glue is a successful technique used for the treatment of bleb dysfunction. The major advantages compared with other techniques are preservation of IOP control and reduced post-operative complications, such as wound leak and the need for re-suturing

Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling

The conserved polarity complex, comprising the partitioning-defective (Par) proteins Par3 and Par6, and the atypical protein kinase C, functions in various cell-polarization events and asymmetric cell divisions. However, little is known about whether and how external stimuli-induced signals may regulate Par3 function in epithelial cell polarity. Here, we found that Par3 was tyrosine phosphorylated through phosphoproteomic profiling of pervanadate-induced phosphotyrosine proteins. We also demonstrated that the tyrosine phosphorylation event induced by multiple growth factors including epidermal growth factor (EGF) was dependent on activation of Src family kinase (SFK) members c-Src and c-Yes. The tyrosine residue 1127 (Y1127) of Par3 was identified as the major EGF-induced phosphorylation site. Moreover, we found that Y1127 phosphorylation reduced the association of Par3 with LIM kinase 2 (LIMK2), thus enabling LIMK2 to regulate cofilin phosphorylation dynamics. Substitution of Y1127 for phenylalanine impaired the EGF-induced Par3 and LIMK2 dissociation and delayed epithelial tight junction (TJ) assembly considerably. Collectively, these data suggest a novel, phosphotyrosine-dependent fine-tuning mechanism of Par3 in epithelial TJ assembly controlled by the EGF receptor-SFK signaling pathway