Peri-ampullary mixed acinar-endocrine carcinoma

Mixed acinar-endocrine carcinomas (MAEC) are rare tumors of the pancreas. We present the case of a patient with periampullary tumor that presented with painless jaundice and after investigation was found to have MAEC. He underwent pancreaticoduo-dunectomy with tumor free margins and negative lymph nodes. The patient presented with local recurrence and liver metastasis after 1 year and is on chemotherapy with stable lesions 30 months after the diagnosis

Diagnostics techniques in nonmuscle invasive bladder cancer

Introduction: Nonmuscle invasive bladder cancer (NMIBC) is the most common presentation of bladder cancer and is often treatable with endoscopic resection and intravesical therapies. Cystoscopy and urine cytology are the gold standard in diagnosis and surveillance but are limited by their sensitivity in some situations. We seek to provide an overview of recent additions to the diagnostic armamentarium for urologists treating this disease. Methods: Articles were identified through a literature review of articles obtained through PubMed searches including the terms “bladder cancer”and various diagnostic techniques described in the article. Results: A variety of urinary biomarkers are available to assist the diagnosis and management of patients with NMIBC. Many have improved sensitivity over urine cytology, but less specificity. There are certain situations in which this has proved valuable, but as yet these are not part of the standard guidelines for NMIBC. Fluorescence cystoscopy has level 1 evidence demonstrating increased rates of tumor detection and prolonged recurrence-free survival when utilized for transurethral resection. Other technologies seeking to enhance cystoscopy, such as narrow band imaging, confocal laser endomicroscopy, and optical coherence tomography are still under evaluation. Conclusions: A variety of urine biomarker and adjunctive endoscopic technologies have been developed to assist the management of NMIBC. While some, such as fluorescence cystoscopy, have demonstrated a definite benefit in this disease, others are still finding their place in the diagnosis and treatment of this disease. Future studies should shed light on how these can be incorporated to improve outcomes in NMIBC

Methods for managing erectile function in cis- and trans-male patients after neophallus reconstruction

Understanding the methods and rationale for managing erectile function in cis- and trans-male patients after neophallus reconstruction is of clinical value to the practicing urologists who encounter such patients. We describe a brief overview of the urologist’s role in the management of sexual function. This communication focuses on pre- and post- construction of a neophallus, considerations for surgical techniques that are largely dependent on whether the patient is cis- or transgender, the traditional method of placing of inflatable penile prosthesis in a neophallus, and in conjunction with the management of complications post implantation. This manuscript is both a review of the current literature in the field, as well as an overview of experience gained from managing a cohort of patients over the years. Additionally, we discuss novel advances that aim to decrease the risk of complications, including distal erosion of the cylinders of the penile prostheses and the proximal dislodgement of cylinders in these unique patients

Two heterozygous mutations in NFATC1 in a patient with Tricuspid Atresia.

Tricuspid Atresia (TA) is a rare form of congenital heart disease (CHD) with usually poor prognosis in humans. It presents as a complete absence of the right atrio-ventricular connection secured normally by the tricuspid valve. Defects in the tricuspid valve are so far not associated with any genetic locus, although mutations in numerous genes were linked to multiple forms of congenital heart disease. In the last decade, Knock-out mice have offered models for cardiologists and geneticists to study the causes of congenital disease. One such model was the Nfatc1(-/-) mice embryos which die at mid-gestation stage due to a complete absence of the valves. NFATC1 belongs to the Rel family of transcription factors members of which were shown to be implicated in gene activation, cell differentiation, and organogenesis. We have previously shown that a tandem repeat in the intronic region of NFATC1 is associated with ventricular septal defects. In this report, we unravel for the first time a potential link between a mutation in NFATC1 and TA. Two heterozygous missense mutations were found in the NFATC1 gene in one indexed-case out of 19 patients with TA. The two amino-acids changes were not found neither in other patients with CHDs, nor in the control healthy population. Moreover, we showed that these mutations alter dramatically the normal function of the protein at the cellular localization, DNA binding and transcriptional levels suggesting they are disease-causing

NFATC1 mutations impair functional interactions with GATA5 and HAND2.

<p>A- Wt NFATC1 or NFATC1 Mutants (P66L, I701L, P66L/I701L) were transfected with/without HAND2 and the DEGS1 promoter coupled to luciferase reporter construct in Hela cells. Six hours post transfection, media was changed and cells were harvested for luciferase assay after 36 hours. Relative luciferase activities are represented as fold activation. The data are the mean of three independent experiments done in duplicates +/− standard deviation. Wt NFATC1 and HAND2 synergistically activate DEGS1 promoter. This synergy was abrogated in all NFATC1 mutants. Significance (p<0.05) was assessed using the one-way Anova test. (* p<0.01, ** p<0.05) B- Wt NFATC1 or NFATC1 Mutants (P66L, I701L, P66L/I701L) were transfected with/without PPP3CA and with/without GATA5 to assess their combinatorial regulation of the DEGS1 promoter in HeLa cells. Six hours post transfection, media was changed and cells were harvested for luciferase assay after 36 hours. Relative luciferase activities are represented as fold activation. The data are the mean of three independent experiments done in duplicates +/− standard deviation. Wt NFATC1 cotransfected with GATA5 caused a synergistic activation of 35 fold, while transfection of Wt NFATC1 with PPP3CA and GATA5 caused even a stronger synergy reaching 68 fold. The synergestic activation was maintained in all mutants except for P66L/I701L double mutant where the synergy was totally lost. Significance (p<0.05) was assessed using the one-way Anova test. (* p<0.01, ** p<0.05).</p

Hypothetical pathway involving NFATC1 in endocardial cushion proliferation and valve maturation.

<p>Hypothetical pathway involving NFATC1 in endocardial cushion proliferation and valve maturation.</p