Complex Ventral Hernias: A Review of Past to Present.

With the incidence of ventral hernias increasing, surgeons are faced with greater complexity in dealing with these conditions. Proper knowledge of the history and the advancements made in managing complex ventral hernias will enhance surgical results. This review article highlights the literature regarding complex ventral hernias, including a shift from a focus that stressed surgical technique toward a multimodal approach, which involves optimization and identification of suboptimal characteristics.

Operative outcomes of infantile hypertrophic pyloric stenosis in patients with congenital heart disease.

PURPOSE: This study aims to compare the outcomes of pyloromyotomy for infantile hypertrophic pyloric stenosis (IHPS) in children with and without congenital heart disease (CHD). METHODS: A retrospective, single pediatric center, case-control, matched cohort study was performed over 10years. A case of IHPS with CHD was paired with control patients of IHPS without CHD, matched by age and gender. Perioperative morbidity, 30-day mortality, length of hospital stay, and hospital cost were compared. Subgroups were analyzed based on the severity of CHD and the reason for admission. RESULTS: Twenty-six patients who underwent pyloromyotomy for IHPS with CHD (CHD group) were matched with 78 patients with IHPS without CHD (Non-CHD group). No 30-day mortality was identified in either group. Overall perioperative complications were not significantly different between groups (11.5% vs 5.2%, p=0.163). However, postoperative length of stay was longer in CHD group (6 vs 1days, p<0.001) and any subgroups of CHD as compared to Non-CHD group. CHD group patients admitted only for IHPS had short postoperative LOS, whereas those who developed pyloric stenosis during a hospital admission stayed longer postoperatively (1.5 vs 26.5days, p<0.001). Mean hospital costs in patients admitted for IHPS were $16,270 and $3591 for CHD group and Non-CHD group, respectively (p<0.001). CONCLUSIONS: IHPS patients with CHD have prolonged postpyloromyotomy course, especially when inpatients with CHD incidentally develop IHPS.

Post traumatic pulmonary pseudoaneurysm requiring pneumonectomy: a case report.

A 57-year-old male presented with progressive exertional dyspnea, cough, and hemoptysis. He underwent a chest computed tomography (CT) that demonstrated a 27 cm × 20 cm right chest mass that was causing a local mass effect. Pertinent history revealed that the patient had suffered a severe chest trauma from a MVA in 1981. The patient underwent workup including: needle localized biopsy, bronchoscopy and endoscopic biopsy. There was considerable concern for a malignant process and a subsequent right pneumonectomy with en bloc resection of the chest wall and diaphragm was performed. The final pathology concluded the mass to be a large pseudoaneurysm. Pseudoaneurysms after traumas are extremely rare, especially blunt trauma, and should be considered once other etiologies have been excluded.

A high-fat diet is associated with altered adipokine production and a more aggressive esophageal adenocarcinoma phenotype in vivo.

OBJECTIVE: Obesity has been linked to esophageal adenocarcinoma (EAC). We hypothesize that adipokines, which are altered by obesity, could affect EAC growth rates and potentially serve as biomarkers of disease and targets for treatment. We have developed a potential murine model to investigate the effects of obesity-altered adipokines on EAC in vivo. METHODS: Severe combined immune-deficient mice were fed either a high-fat diet (HFD) containing 60% animal fat, or a control diet with 10% animal fat, and monitored for weight gain for 5 weeks. All mice were subcutaneously implanted with EAC cells (OE33), and tumor volume was monitored for an additional 4 weeks by direct measurement and uptake of fluorescently labeled 2-D-deoxyglucose. At sacrifice, serum triglyceride levels and abdominal fat-pad weight were measured to assess obesity state. Adipokine levels were measured within abdominal fat of tumor-bearing mice. RESULTS: Mice fed the HFD displayed increased body weight, visceral fat, and serum leptin and triglycerides. All mice developed tumors; OE33 EAC cells in HFD mice displayed increased growth rates, proliferation, and metabolic activity relative to tumors of EAC in control diet mice. Adipokine expression in the abdominal fat revealed distinct changes associated with the HFD and increased body weight. CONCLUSIONS: Ad libitum feeding of the HFD was correlated with more-proliferative EAC tumors in vivo. This phenotype was associated with alterations to secreted adipokines, representing a potential mechanism for our observations. Further studies are necessary to explore findings, as they have potential to improve treatment of EAC.

An immunofluorescent method for characterization of Barrett's esophagus cells.

Esophageal adenocarcinoma (EAC) has an overall survival rate of less than 17% and incidence of EAC has risen dramatically over the past two decades. One of the primary risk factors of EAC is Barrett's esophagus (BE), a metaplastic change of the normal squamous esophagus in response to chronic heartburn. Despite the well-established connection between EAC and BE, interrogation of the molecular events, particularly altered signaling pathways involving progression of BE to EAC, are poorly understood. Much of this is due to the lack of suitable in vitro models available to study these diseases. Recently, immortalized BE cell lines have become commercially available allowing for in vitro studies of BE. Here, we present a method for immunofluorescent staining of immortalized BE cell lines, allowing in vitro characterization of cell signaling and structure after exposure to therapeutic compounds. Application of these techniques will help develop insight into the mechanisms involved in BE to EAC progression and provide potential avenues for treatment and prevention of EAC.

LKB1 inactivation sensitizes non-small cell lung cancer to pharmacological aggravation of ER stress.

Five-year survival rates for non-small cell lung cancer (NSCLC) have seen minimal improvement despite aggressive therapy with standard chemotherapeutic agents, indicating a need for new treatment approaches. Studies show inactivating mutations in the LKB1 tumor suppressor are common in NSCLC. Genetic and mechanistic analysis has defined LKB1-deficient NSCLC tumors as a phenotypically distinct subpopulation of NSCLC with potential avenues for therapeutic gain. In expanding on previous work indicating hypersensitivity of LKB1-deficient NSCLC cells to 2-deoxy-D-glucose (2DG), we find that 2DG has in vivo efficacy in LKB1-deficient NSCLC using transgenic murine models of NSCLC. Deciphering of the molecular mechanisms behind this phenotype reveals that loss of LKB1 in NSCLC cells imparts increased sensitivity to pharmacological compounds that aggravate ER stress. In comparison to NSCLC cells with functional LKB1, treatment of NSCLC cells lacking LKB1 with the ER stress activators (ERSA), tunicamycin, brefeldin A or 2DG, resulted in aggravation of ER stress, increased cytotoxicity, and evidence of ER stress-mediated cell death. Based upon these findings, we suggest that ERSAs represent a potential treatment avenue for NSCLC patients whose tumors are deficient in LKB1.

Management of locally advanced renal cell carcinoma with invasion of the duodenum.

Renal cell carcinoma (RCC) is rare but aggressive, with greater than 20% of patients presenting with stage III or IV, disease. Surgical resection of the primary tumor regardless of stage is the treatment of choice, and en bloc resection of involved organs provides the only potential chance for cure. This case report describes a patient with metastatic right-sided RCC with invasion of the inferior vena cava and duodenum managed by en block resection and pancreaticoduodenectomy. This report will review the workup and treatment of locally advanced RCC, as well as the role of cytoreductive nephrectomy in the setting of metastatic disease.

Dasatinib, a small molecule inhibitor of the Src kinase, reduces the growth and activates apoptosis in pre-neoplastic Barrett's esophagus cell lines: evidence for a noninvasive treatment of high-grade dysplasia.

BACKGROUND: Only local ablation (radiofrequency ablation, cryotherapy) or esophagectomy currently is available to treat high-grade dysplasia in Barrett's esophagus. Alternative treatments, specifically chemopreventive strategies, are lacking. Our understanding of the molecular changes of high-grade dysplasia in Barrett's esophagus offers an opportunity to inhibit neoplastic progression of high-grade dysplasia in Barrett's esophagus. Increased activity of the Src kinase and deregulation of the tumor suppressor p27 are features of malignant cells and high-grade dysplasia in Barrett's esophagus. Src phosphorylates p27, inhibiting its regulatory function and increasing cell growth and proliferation. We hypothesized that a small molecule inhibitor of Src might reduce the growth and reverse Src-mediated deregulation of p27 in Barrett's esophagus cells. METHODS: Immortalized Barrett's esophagus cell lines established from patient biopsies were treated with the Src kinase inhibitor dasatinib and evaluated for p27 localization and protein levels, as well as for effects on the cell cycle and apoptosis using flow cytometry, viability assays, and protein and RNA markers. RESULTS: Dasatinib reduced both Src activation and p27 phosphorylation and increased p27 protein levels and nuclear localization. These effects correlated with decreased proliferation, cell-cycle arrest, and activation of apoptosis. Analysis of biopsies of patients with Barrett's esophagus revealed the presence of phosphorylated p27 in high-grade dysplasia, consistent with in vitro findings. CONCLUSIONS: Dasatinib has considerable antineoplastic effects on Barrett's esophagus cell lines carrying genetic markers associated with dysplasia, which correlates with the reversal of p27 deregulation. These findings suggest that dasatinib has potential as a treatment for patients with high-grade dysplasia and Barrett's esophagus and that p27 holds promise as a biomarker in the clinical use of dasatinib in patients with high-grade dysplasia and Barrett's esophagus.