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Introduction: Supracondylar fractures of the humerus are the commonest upper limb fractures in children, accounting for up to 70% of all pediatric elbow fractures. Supracondylar fractures of the humerus can be managed in outpatient setting but are often complicated by neurovascular injury. Methods: Retrospective study including 187 patients who had presented with supracondylar fracture of humerus with 47 neurovascular injuries during the period of July 2007 to June 2011. Out of 142 patients with Gartland type III fracture 107 underwent immediate open reduction, exploration and internal fixation. Results: Vascular injury is commonly associated with type II supracondylar fracture with posterior displacement. Twenty two patients had vascular injury and all of them had satisfactory outcome after surgery. Conclusion: A careful clinical evaluation, urgent surgical treatment and adequate fracture reduction can prevent lifelong handicap. [ABSTRACT FROM AUTHOR]

Introduction: Pseudoaneurysms are major vascular complications in intravenous drug abusers. They are potentially fatal, often infected and require urgent management. Method: This is a retrospective study of the prevalent practice of their management in our center. The inpatient medical charts of the patients spanning 5 years (Sep 2006 to Aug 2011) were reviewed. Data were obtained on their demographic, clinical, management and outcome parameters. Result: Among the thirty intravenous drug users presenting with pseudoaneurysms (excluding one who bled to death before surgery), 28 had their femoral artery involved. Most of them (90%) were infected. Nearly half of the patients (45%) were seropositive for HIV and/or HCV. All were operated, with no mortality. Ligation and debridement was the technique used almost exclusively (83%). One brachial artery was repaired primarily, whereas 3 femoral and 1 brachial pseudoaneurysms were managed with autologous saphenous vein bypass. Five patients had neurological complications, and 5 others had non-limb threatening claudication which got better with medical management. Mean follow up period was 11 months. Conclusion: Ligation and debridement appears to be a simple, safe and effective procedure in infected pseudoaneurysms in IV drug users. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid cancers; thus, identifying more effective therapies is a major unmet need. In this study, we characterized the super enhancer (SE) landscape of human PDAC to identify drivers of the disease that might be targetable. This analysis revealed MICAL2 as a super enhancer-associated gene in human PDAC, which encodes the flavin monooxygenase MICAL2 that induces actin depolymerization and indirectly promotes SRF transcription by modulating the availability of serum response factor coactivators myocardin-related transcription factors (MRTF-A and MRTF-B). MICAL2 was overexpressed in PDAC, and high MICAL2 expression correlated with poor patient prognosis. Transcriptional analysis revealed that MICAL2 upregulates KRAS and EMT signaling pathways, contributing to tumor growth and metastasis. In loss and gain of function experiments in human and mouse PDAC cells, MICAL2 promoted both ERK1/2 and AKT activation. Consistent with its role in actin depolymerization and KRAS signaling, loss of MICAL2 also inhibited macropinocytosis. MICAL2, MRTF-A, and MRTF-B influenced PDAC cell proliferation and migration and promoted cell cycle progression in vitro. Importantly, MICAL2 supported in vivo tumor growth and metastasis. Interestingly, MRTF-B, but not MRTF-A, phenocopied MICAL2-driven phenotypes in vivo. This study highlights the multiple ways in which MICAL2 impacts PDAC biology and provides a foundation for future investigations into the potential of targeting MICAL2 for therapeutic intervention.

A majority of cancer research is focused on defining the cellular and molecular basis of cancer cells and the signals that control oncogenic transformation; as a consequence, we know very little about the dynamic behavior of cancer cells in vivo. To begin to view and understand the mechanisms and interactions that control cancer initiation, growth, and metastatic progression and how these processes are influenced by the microenvironment and the signals derived from it, it is essential to develop strategies that allow imaging of the cancer cells in the context of the living microenvironment. Here, we discuss emerging work designed to visualize how cancer cells function within the microenvironment to discover how these interactions act coordinately to enable aberrant growth and to understand how they could be targeted to design new approaches to intercept the disease., (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)

Interleukin-6 (IL-6)-class inflammatory cytokines signal through the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and promote the development of pancreatic ductal adenocarcinoma (PDAC); however, the functions of specific intracellular signaling mediators in this process are less well defined. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate in this study that JAK1 deficiency prevents the formation of KRAS G12D -induced pancreatic tumors, and we establish that JAK1 is essential for the constitutive activation of STAT3, whose activation is a prominent characteristic of PDAC. We identify CCAAT/enhancer binding protein δ (C/EBPδ) as a biologically relevant downstream target of JAK1 signaling, which is upregulated in human PDAC. Reinstating the expression of C/EBPδ was sufficient to restore the growth of JAK1-deficient cancer cells as tumorspheres and in xenografted mice. Collectively, the findings of this study suggest that JAK1 executes important functions of inflammatory cytokines through C/EBPδ and may serve as a molecular target for PDAC prevention and treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Identifying the cells from which cancers arise is critical for understanding the molecular underpinnings of tumor evolution. To determine whether stem/progenitor cells can serve as cells of origin, we created a Msi2-Cre ERT2 knock-in mouse. When crossed to CAG-LSL-Myc T58A mice, Msi2-Cre ERT2 mice developed multiple pancreatic cancer subtypes: ductal, acinar, adenosquamous, and rare anaplastic tumors. Combining single-cell genomics with computational analysis of developmental states and lineage trajectories, we demonstrate that MYC preferentially triggers transformation of the most immature MSI2 + pancreas cells into multi-lineage pre-cancer cells. These pre-cancer cells subsequently diverge to establish pancreatic cancer subtypes by activating distinct transcriptional programs and large-scale genomic changes, and enforced expression of specific signals like Ras can redirect subtype specification. This study shows that multiple pancreatic cancer subtypes can arise from a common pool of MSI2 + cells and provides a powerful model to understand and control the programs that shape divergent fates in pancreatic cancer., Competing Interests: Declaration of interests T.R. is a founder and member of the Board of Directors, and holds executive roles at Tiger Hill Therapeutics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pancreatic cancer is characterized by extensive resistance to conventional therapies, making clinical management a challenge. Here we map the epigenetic dependencies of cancer stem cells, cells that preferentially evade therapy and drive progression, and identify SWI/SNF complex member SMARCD3 as a regulator of pancreatic cancer cells. Although SWI/SNF subunits often act as tumor suppressors, we show that SMARCD3 is amplified in cancer, enriched in pancreatic cancer stem cells and upregulated in the human disease. Diverse genetic mouse models of pancreatic cancer and stage-specific Smarcd3 deletion reveal that Smarcd3 loss preferentially impacts established tumors, improving survival especially in context of chemotherapy. Mechanistically, SMARCD3 acts with FOXA1 to control lipid and fatty acid metabolism, programs associated with therapy resistance and poor prognosis in cancer. These data identify SMARCD3 as an epigenetic modulator responsible for establishing the metabolic landscape in aggressive pancreatic cancer cells and a potential target for new therapies., (© 2023. The Author(s).)

Objective: To describe 5 cases with complete urinary bladder duplication, their associated conditions, and their respective treatment. Urinary bladder duplication is an extremely rare congenital anomaly of the urinary system. So far about 70 cases have been published in the English literature, most of them as case reports and a few case series., Methods and Results: All consecutive patients with bladder duplication treated at our institution between 2000 and 2015 were included. Patient records were retrospectively analyzed, and 5 patients with urinary bladder duplication were identified (see Summary Figure). Two patients were male. All duplications were recognized by health care providers. In 1 case recognition was prenatal (MRI in utero at 22 weeks of gestation), the latest recognition was at 12 months of age. A voiding cystourethrography was performed in 4 patients to confirm the diagnosis. In 4 patients the bladder duplication could be classified according to Abrahamson with 3 complete reduplications and one complete sagittal septum. All patients suffered from associated congenital diseases, but only one patient had urinary tract infections. Surgical treatment was only performed in one patient. Median follow-up was 34 months., Discussion: Urinary bladder duplications reflect extremely seldom disorders that are almost always associated with other congenital anomalies. Treatment depends on patients' symptoms and associated conditions and hence needs to be individualized to each patient., (Copyright © 2020. Published by Elsevier Inc.)

Background: Single-port, laparoscopic, needle-assisted, inguinal hernia repair (LNAR) in children intends to reduce surgical trauma and enables contralateral assessment and closure of contralateral patent processus vaginalis if necessary. The aim of the present study was to demonstrate that laparoscopic inguinal repair can be performed safely and cost-effectively in a developing country where laparoscopy is not yet commonly used. Methods: In this single-center study, we included all children undergoing LNAR between January 2017 and December 2018. Intraoperative and postoperative complications and hospital costs were assessed. Results: We performed 148 hernia repair operations in 117 children (age range 1 month to 15 years). Mean operative time was 20.8 ± 9.4 minutes. Mean length of hospital stay amounted to 10 ± 7.6 hours, with 77.7% of patients discharged within 6 hours. No intraoperative complications occurred in any patient. Complications occurred in six (5.1%) patients. Three (2.5%) patients experienced residual hydrocele, two (1.4%) patients suffered wound site seroma, and one (0.67%) patient experienced recurrent inguinal hernia 6 months after the initial repair. All complications occurred during the first year of the study period. Likewise, operative time ( P  < .0001) as well as duration of hospital stay ( P  < .0001) was significantly shorter in the second year. Total costs for complete treatment were below USD 80 per patient, which is comparable with the costs associated with open herniotomy at the same institution. Conclusion: Single-port LNAR and hydrocele repair in children were established safely and cost-effectively in a developing country. Nevertheless, the procedure was associated with a steep learning curve.

Background Myocardial revascularization surgery has shown better long term survival expectancy compared to medical therapy in patient with impaired left ventricular function. Objective To evaluate the change in ejection fraction after 90 days in patients who underwent coronary artery bypass surgery and had preoperative left ventricular ejection fraction of less than and equal to 45% in a single cardiac center of Nepal over the period of 2 years. Method Out of 82 eligible patients during 2 years, 3 patients expired in immediate postoperatively and 24 patients had loss of 90 days' follow up. So, they were excluded from the study. Total 55 patients were taken for the study for whom statistical analysis was done to compare preoperative ejection fraction with post-operative 90 days' ejection fraction. Result Single vessel disease was present in 2(3.6%) patients, double vessel disease in 7(12.7%) patients and triple vessel disease in 46(83.6%) of the patients. In 2(3.6%) patients 2 grafts, in 18(32.7%) patients 3 grafts, in 33(60%) patients 4 grafts and in 2(3.6%) patients 5 grafts were placed for revascularization. The mean left ventricular EF in preoperative patients was 37.12±5.69% which improved to 45.80±10.00% in postoperative follow up at 90 days which was statistically significant (p=0.000). Conclusion Surgical revascularization of myocardium in preoperatively impaired left ventricular function patients helps improve left ventricular ejection fraction postoperatively. So we suggest surgical revascularization in patient with low ejection fraction for improvement of myocardial function. Hence improve survival rate in these patients.

A thrombus straddling the foramen ovale is rare; and optimal management is controversial. Most of the literature on this topic is available only in the form of case reports. Here, we present a case of 30-year-old female with recent history of fibular fracture and thrombus in transit through patent foramen ovale and massive pulmonary embolism who was successfully managed with pulmonary embolectomy, extraction of serpentine thrombus straddling patent foramen ovale, and closure of patent foramen ovale., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2020.)

Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well-characterized genomic lesions including mutations in TP53 (87%) and KRAS (73%), amplification of MYC (47%), and homozygous deletion of CDKN2A (40%) that are common in PDACs. Furthermore, a comparison of ATAC-seq profiles of three ASCP and three PDAC genomes using flow-sorted PDX models identified genes with accessible chromatin unique to the ASCP genomes, including the lysine methyltransferase SMYD2 and the pancreatic cancer stem cell regulator RORC in all three ASCPs, and a FGFR1-ERLIN2 fusion associated with focal CNVs in both genes in a single ASCP. Finally, we demonstrate significant activity of a pan FGFR inhibitor against organoids derived from the FGFR1-ERLIN2 fusion-positive ASCP PDX model. Our results suggest that the genomic and epigenomic landscape of ASCP provide new strategies for targeting this aggressive subtype of pancreatic cancer. SIGNIFICANCE: These data provide a unique description of the ASCP genomic and epigenomic landscape and identify candidate therapeutic targets for this dismal cancer., (©2020 American Association for Cancer Research.)

Background: Laparoscopic cholecystectomy is responsible for 80-85% of the bileduct injury, and twice as frequentcompared to open cholecystectomy.Injury affects the quality of life and overall survival of the patient. The management of these injuries is complex and challenging. There are few locally published reports regarding management of bile duct injury. The objective of this study is to evaluate the management of bile duct injury and its outcome Methods: This retrospective study includes patients bile duct injury following cholecystectomy who were managed at Dhulikhel Hospital, Nepal, during January 2014 to December 2016. The clinical features, type of injuries(Strasberg classification) management, outcome (as per McDonald and colleague grading system) and follow up were analyzed descriptively., Results: Out of 35 bile duct injuries,only 3 (8.57%)occurred following open cholecystectomy. Three (8.7%) cases of bile duct injury were diagnosed intraoperatively and had primary biliary anastomosis over T-tube. Five (14.28%) were diagnosed postoperatively and underwent Roux-en-y hepatojejunostomy 6 weeks after index surgery. And, 27(77.14%) with type A injuries were treated by endoscopic retrograde cholangio-pancreatography and stenting. After surgical repair, 1 (2.85%) had transient biliary leak. One patient had grade B outcome. During 18 months follow up, no stricture or cholangitis were observed., Conclusions: Bile duct injury with intact continuity of the duct can be successfully managed with endoscopic stenting of the biliary tree. Intraoperative diagnosis of bile duct injury and immediate surgical management has good outcome.

Background Ductus arteriosus is a vascular structure which connects the roof of main pulmonary artery near the origin of the left branch pulmonary artery to the proximal descending aorta. Patent ductus arteriosus (PDA) closure is indicated for any patient who is symptomatic from left to right shunting. Objective To investigate the hospital outcomes of surgical closure of patent ductus arteriosus over last 19 years starting from the very first case of our center. Method This is a retrospective analysis of all patent ductus arteriosus treated surgically from August 2001 to July 2019. Patients who underwent isolated surgical closure of patent ductus arteriosus were included. Data have been presented in three different eras (Era 1: 2001-2007, Era 2: 2008-2013, and Era 3: 2014-2019) to see the trend of evolution of this surgery. Result A total of 901 patients aged 8.67±8.76 years under went patent ductus arteriosus surgical closure over last 19 years. Patients in the initial era 2001-2007 were significantly older compared with other 2 eras (p=0.000). Males accounted for 35.5% of all cases. Twenty percent had severe pulmonary artery hypertension.Duration of mechanical ventilation was 3.57±9.64 hours with ICU stay of 1.55±1.53 days, and hospital stay of 3.9±2.3 days. Overall in hospital mortality was 0.8%; for isolated patent ductus arteriosus diagnosis, mortality was 0.2%. Chylothorax was noted in 0.4%. Conclusion This is the first report to analyze surgical outcomes of patent ductus arteriosus ligation in our center. We have discussed the evolution of patent ductus arteriosus surgery in our center, and have shown favorable outcomes in terms of morbidity and mortality.

We report a case of a 42-year-old man with a submitral aneurysm who presented to the emergency room in circulatory collapse, with left ventricular obstruction and severe mitral valve stenosis and regurgitation secondary to the aneurysm. Resection of the aneurysm and mitral valve replacement were performed through a median sternotomy without any complication and with good results., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Drug resistance and relapse remain key challenges in pancreatic cancer. Here, we have used RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP)-seq, and genome-wide CRISPR analysis to map the molecular dependencies of pancreatic cancer stem cells, highly therapy-resistant cells that preferentially drive tumorigenesis and progression. This integrated genomic approach revealed an unexpected utilization of immuno-regulatory signals by pancreatic cancer epithelial cells. In particular, the nuclear hormone receptor retinoic-acid-receptor-related orphan receptor gamma (RORγ), known to drive inflammation and T cell differentiation, was upregulated during pancreatic cancer progression, and its genetic or pharmacologic inhibition led to a striking defect in pancreatic cancer growth and a marked improvement in survival. Further, a large-scale retrospective analysis in patients revealed that RORγ expression may predict pancreatic cancer aggressiveness, as it positively correlated with advanced disease and metastasis. Collectively, these data identify an orthogonal co-option of immuno-regulatory signals by pancreatic cancer stem cells, suggesting that autoimmune drugs should be evaluated as novel treatment strategies for pancreatic cancer patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Primary cardiac tumors are rare and when they occur, 75% are benign. Atrial myxomas having a good prognosis compromise 50% of all primary cardiac tumors. Only 25% of the primary cardiac tumors are malignant and 75% of these malignant tumors are sarcomas. Sarcomas often occur in young patients without any predisposing factors and tend to have very poor prognosis. We present an unfortunate case of a young female with high-grade spindle cell sarcoma. She was initially diagnosed to have mitral valve pathology and hypertrophic cardiomyopathy but confirmation of diagnosis was made only after a second operation and patient's demise., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2018.)

Background: Posttubercular constrictive pericarditis is prevalent pericardial disease in developing countries. Pericardiectomy is the treatment of choice but considered a procedure of high morbidity and mortality., Methods: From January 2003 to December 2013 we performed 130 pericardiectomies. The patients' mean age was 22.95 ± 12.55 years, and there were 92 (71%) male patients. All patients were symptomatic; 118 (91%) were in New York Heart Association functional class III or IV. Almost all patients were diagnosed to be of tubercular origin: 14 (11%) were histopathologically proven, 77 (59%) had definitive history, 39 (30%) were suspected to be of tubercular origin, and 91 (70%) received prior antitubercular treatment., Results: Anterior pericardiectomy was done without the use but with provision for cardiopulmonary bypass, which was required in 5 (3.8%) patients for repair of tear in right atrium. Following pericardiectomy central venous pressure dropped from 20.9 to 10.8 mm Hg. Early mortality was 10 (7.69%). Prolonged ventilation was required in 22 (16.92%) patients, 31 (23.84%) developed renal dysfunction, and there were 3 (3.12%) cases of new-onset atrial fibrillation. On analysis of univariate predictors for early mortality, low ejection fraction (p < 0.001) and preoperative atrial fibrillation (p < 0.001) were found to be significant. In a follow-up of 12 months, 85% patients were in New York Heart Association functional class I or II with mean ejection fraction of 52%. There was no recurrence of constriction from residual pericardium on 1-year follow-up., Conclusions: Anterior pericardiectomy is sufficient in patients with constrictive pericarditis of infective etiology. Preoperative low ejection fraction, atrial fibrillation, poor functional class, and constrictive effusive pericarditis results in poor surgical outcome., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Mutant KRAS and c-MYC are oncogenic drivers and rational therapeutic targets for the treatment of pancreatic cancer. Although tumor growth and homeostasis are largely dependent on these oncogenes, a few residual cancer cells are able to survive the ablation of mutant KRAS and c-MYC. By performing a genome-wide gene expression analysis of in vivo-derived bulk tumor cells and residual cancer cells lacking the expression of mutant KRAS or c-MYC, we have identified an increase in autocrine IGF1/AKT signaling as a common survival mechanism in dormant cancer cells. The pharmacological inhibition of IGF-1R reduces residual disease burden and cancer recurrence, suggesting that this molecular pathway is crucial for the survival of cancer cells in the absence of the primary oncogenic drivers., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite a wealth of knowledge about the significance of individual signal transducers and activators of transcription (STATs), essential functions of their upstream Janus kinases (JAKs) during postnatal development are less well defined. Using a novel mammary gland-specific JAK1 knockout model, we demonstrate here that this tyrosine kinase is essential for the activation of STAT1, STAT3, and STAT6 in the mammary epithelium. The loss of JAK1 uncouples interleukin-6-class ligands from their downstream effector, STAT3, which leads to the decreased expression of STAT3 target genes that are associated with the acute-phase response, inflammation, and wound healing. Consequently, JAK1-deficient mice exhibit impaired apoptosis and a significant delay in mammary gland remodeling. Using RNA sequencing, we identified several new JAK1 target genes that are upregulated during involution. These include Bmf and Bim, which are known regulators of programmed cell death. Using a BMF/BIM-double-knockout epithelial transplant model, we further validated that the synergistic action of these proapoptotic JAK1 targets is obligatory for the remodeling of the mammary epithelium. The collective results of this study suggest that JAK1 has nonredundant roles in the activation of particular STAT proteins and this tyrosine kinase is essential for coupling inflammatory cytokine signals to the cell death machinery in the differentiated mammary epithelium., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Introduction: Cerebral ventricular enlargement occurs as a natural aging process but also has been associated with many neurological disorders. Whether this enlargement is primary or secondary to these pathological conditions remains controversial. Objective of the study was to tabulate and create normal references values for maximum width of third ventricle in Nepalese population according to age group and gender., Methods: MTW was determined in two hundred (112 males and 88 females) and age ranging between 1- 93 years who had normal Computed tomography scan of the head .The data collected was analyzed with statistical program IBM SPSS version 20., Results: Measurements of MTW in both males and females of the normal groups revealed no significant difference. No significant difference in MTW was noticed till the age of 49 years. Significant differences were noticed between 49 - 93 years of age., Conclusions: This study corroborated well with normal MTW values published in literatures from other parts of the world. However normal values specific to our local population becomes more relevant in interpreting CT scan of head in Nepal.

Significant advances have been made in the identification of key molecular pathways that play pivotal roles in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). Among the common genetic and epigenetic changes, oncogenic mutations in Kras and upregulation of the c-Myc oncogene are frequent events in PDAC. Using genetically defined in vivo models, several studies have recently demonstrated that expression of mutant Kras and c-Myc is equally important for the initiation and maintenance of pancreatic cancer. The targeted downregulation of a single oncogene resulted in cancer cell death at primary and metastatic sites. These findings are very encouraging and provide a strong rationale for the development of targeted therapies against these oncogenic drivers. Despite what seemed to be a complete response to the ablation of the oncogene, a few dormant cancer cells remained present, and it was demonstrated that they are a cellular reservoir for a swift relapse of pancreatic cancer following oncogene reactivation. This review summarizes the basic principles of cancer dormancy and the applicability of the novel genetic models for reversible metastatic PDAC to elucidate the role of cancer stem cells as well as biologic and molecular mechanisms that mediate the survival of dormant tumor cells., (©2014 AACR.)

The initiation and progression of pancreatic ductal adenocarcinoma (PDAC) is governed by a series of genetic and epigenetic changes, but it is still unknown whether these alterations are required for the maintenance of primary and metastatic PDAC. We show here that the c-Myc oncogene is upregulated throughout the entire process of neoplastic progression in human PDAC and in genetically engineered mice that express mutant Kras. To experimentally address whether c-Myc is essential for the growth and survival of cancer cells, we developed a novel mouse model that allows a temporally and spatially controlled expression of this oncogene in pancreatic progenitors and derived lineages of the exocrine pancreas. Unlike previous reports, upregulation of c-Myc was sufficient to induce the formation of adenocarcinomas after a short latency without additional genetic manipulation of cell survival pathways. Deficiency in Cdkn2a increased the rate of metastasis but had no effect on tumor latency or c-Myc-mediated cancer maintenance. Despite a macroscopically complete regression of primary, metastatic, and transplantable tumors following the ablation of c-Myc, some cancer cells remained dormant. A significant number of these residual neoplastic cells expressed cancer stem cell markers, and re-expression of exogenous c-Myc in these cells led to rapid cancer recurrence. Collectively, the results of this study suggest that c-Myc plays a significant role in the progression and maintenance of PDAC, but besides targeting this oncogene or its downstream effectors, additional therapeutic strategies are necessary to eradicate residual cancer cells to prevent disease recurrence.

Microalbuminuria is considered to be an early stage of diabetic nephropathy as well as a marker of cardiovascular disease. The aim of this study was to see the prevalence of microalbuminuria in type 2 diabetic patients and assess its association with cardiovascular risk factors among them. A total of 143 type 2 diabetic patients with the mean age of 56.06 +/- 1.08 years were analysed. The prevalence of microalbuminuria and overt proteinuria was 45.5% and 11.2%, respectively. Prevalence of microalbuminuria in female was marginally higher than in male (p > 0.05). Subjects with microalbuminuria had significantly higher blood pressure (p < 0.001) and duration of diabetes (p < 0.05) compared with normoalbuminuric subjects. High density lipoprotein was found to be significantly lower (p < 0.05) in subjects with microalbuminuria whereas fasting blood sugar, triglyceride, total cholesterol and very low density lipoprotein were marginally higher in microalbuminuric than in normoalbuminuric subjects (p > 0.05). High prevalence of microalbuminuria in diabetic patients and its positive association with blood pressure and altered lipid profile suggests that screening for microalbuminuria is essential for intervention and prevent further complications like end stage renal disease and cardiovascular diseases.