Comparative study of onlay versus sublay mesh repair in the management of ventral hernias.

Ventral hernias with large defects (≥ 2 cm) are managed with tension free mesh repair. The growing consensus that sublay (retrorectus) mesh repair is superior to onlay mesh repair due to fewer complications is based on literature dominated by retrospective studies from high and upper-middle income countries. There is thus a need of more prospective studies from various countries to resolve the controversy. The objective of this study was to compare the outcomes of onlay versus sublay mesh repair in the management of ventral hernias. Our single centre, prospective comparative study set in a low-middle income country comprised of 60 patients with a ventral hernia undergoing open surgical repair using either onlay technique (n = 30) or sublay technique (n = 30). Surgical site infections, seroma formation, recurrence were found in 3.33%, 6.67%, 0% patients in sublay repair group and in 16.67%, 20%, 6.67% patients in onlay repair group respectively. Mean duration of surgery, mean Visual Analogue Scale (VAS) score for chronic pain, mean duration of hospital stay were 46 min, 4.5, 8 days in onlay repair group and 61 min, 4.2, 6 days in sublay repair group respectively. Onlay repair group was associated with shorter duration of surgery. However, sublay repair was associated with lesser rates of surgical site infections, chronic pain and recurrence than onlay repair. Sublay mesh repair had better outcomes than onlay mesh repair for the management of ventral hernias, however superiority of any one technique could not be established.

Prevalence of and factors associated with treatment modification at first cycle in older adults with advanced cancer receiving palliative treatment.

INTRODUCTION: Treatment toxicities are common in older adults with cancer and consequently, treatment modifications are sometimes considered. We evaluated the prevalence and factors associated with treatment modifications at the first cycle in older patients receiving palliative systemic treatment. METHODS: Patients (n = 369) from the GAP 70+ Trial (NCT02054741; PI: Mohile) usual care arm were included. Enrolled patients were aged 70+ with advanced cancer and ≥ 1 Geriatric Assessment (GA) domain impairment. Treatment modification was defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials. Baseline variables included: 1) sociodemographic factors; 2) clinical variables; 3) GA domains; and 4) physician beliefs about life expectancy. Bivariate analyses and multivariable cluster-weighted generalized estimating equation model were conducted to assess the association of baseline variables with cycle 1 treatment modifications. RESULTS: Mean age was 77.2 years (range: 70-94); 62% had lung or gastrointestinal cancers, and 35% had treatment modifications at cycle 1. Increasing age by one year (odds ratio (OR) 1.1, 95% confidence interval [CI] 1.0-1.2), receipt of ≥second line of chemotherapy (OR 1.8, CI 1.1-3.0), functional impairment (OR 1.6, CI 1.1-2.3) and income ≤$50,000 (OR 1.7, CI 1.1-2.4) were independently associated with a higher likelihood of cycle 1 treatment modification. CONCLUSION: Treatment modifications occurred in 35% of older adults with advanced cancer at cycle 1. Increasing age, receipt of ≥second line of chemotherapy, functional impairment, and lower income were independently associated with treatment modifications. These findings emphasize the need for evidence-based regimens in older adults with cancer and GA impairments.

Loss of SWI/SNF Chromatin Remodeling Alters NRF2 Signaling in Non-Small Cell Lung Carcinoma.

The NF-E2-related factor 2 (referred to as NRF2) transcription factor binds antioxidant responsive elements within the promoters of cytoprotective genes to induce their expression. Next-generation sequencing studies in lung cancer have shown a significant number of activating mutations within the NRF2 signaling pathway. Mutations in components of the SWI/SNF chromatin-remodeling complex, a general regulator of transcription using either BRG1 or BRM as the catalytic subunit, also frequently occur in lung cancers. Importantly, low BRG1 expression levels in primary human NSCLC correlated with increased NRF2-target gene expression. Here, we show that loss of SWI/SNF complex function activated a subset of NRF2-mediated transcriptional targets. Using a series of isogenic NSCLC lines with reduced or depleted BRG1 and/or BRM expression, we observed significantly increased expression of the NRF2-target genes HMOX1 and GSTM4. In contrast, expression of the NRF2 target genes NQO1 and GCLM modestly increased following BRM reduction. Chromatin immunoprecipitation showed that BRG1 knockdown led to increased NRF2 binding at its respective ARE sites in the HMOX1 promoter but not in NQO1 and GCLM. Our data demonstrate that loss of BRG1 or BRM in lung cancer results in activation of the NRF2/KEAP1 pathway and HMOX1 expression. Therefore, we provide an additional molecular explanation for why patients harboring BRG1 or BRM mutations show poor prognoses. A better understanding of this mechanism may yield novel insights into the design of targeted treatment modalities. IMPLICATIONS: Our study identifies a novel mechanism for how mutations in the SMARCA4 gene may drive progression of human lung adenocarcinomas.

BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization.

SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of primary human lung non-small cell lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes.

The use of FDTD in establishing in vitro experimentation conditions representative of lifelike cell phone radiation on the spermatozoa.

Recent studies have shown that exposing human semen samples to cell phone radiation leads to a significant decline in sperm parameters. In daily living, a cell phone is usually kept in proximity to the groin, such as in a trouser pocket, separated from the testes by multiple layers of tissue. The aim of this study was to calculate the distance between cell phone and semen sample to set up an in vitro experiment that can mimic real life conditions (cell phone in trouser pocket separated by multiple tissue layers). For this reason, a computational model of scrotal tissues was designed by considering these separating layers, the results of which were used in a series of simulations using the Finite Difference Time Domain (FDTD) method. To provide an equivalent effect of multiple tissue layers, these results showed that the distance between a cell phone and semen sample should be 0.8 cm to 1.8 cm greater than the anticipated distance between a cell phone and the testes.

Choriocarcinoma in a 73-year-old woman: a case report and review of the literature.

INTRODUCTION: Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Most cases present within one year of the antecedent pregnancy (molar or non-molar). However, very rarely, choriocarcinoma can develop from germ cells or from dedifferentiation of endometrial carcinoma into choriocarcinoma. This article concerns a case of choriocarcinoma developing 38 years after the patient's last pregnancy and 23 years after menopause. CASE PRESENTATION: A 73-year-old African-American woman presented with a three-week history of vaginal bleeding. A vaginal mass was seen on pelvic examination. Ultrasonography showed a thickened complex endometrial echo. Her ß-human chorionic gonadotrophin level was found to be elevated (2,704,040 mIU/mL). Vaginal and uterine biopsies were suggestive of choriocarcinoma. Immunohistochemistry tests were positive for ß-human chorionic gonadotrophin as well as cytokeratin and negative for octamer binding transcription factor 3/4 and α-fetoprotein, supporting the diagnosis of choriocarcinoma. A combination of etoposide, methotrexate, and dactinomycin, followed by cyclophosphamide and vincristine (the so-called EMA/CO regimen) was initiated. After seven cycles of chemotherapy, her ß-human chorionic gonadotrophin level dropped below 5 mIU/mL. Our patient is being followed up at our oncology institute. CONCLUSIONS: We report an extremely rare case of choriocarcinoma arising 23 years after menopause. A postmenopausal woman presenting with vaginal bleed from a mass and ß-human chorionic gonadotrophin elevation should be evaluated by immunohistochemical analysis to rule out the possibilities of a germ cell origin of the tumor or dedifferentiation of an epithelial tumor. Absence of octamer binding transcription factor 3/4, α-fetoprotein and CD-30 staining helps in exclusion of most germ cell tumors. DNA polymorphism studies can be used to differentiate between gestational and non-gestational tumor origin. These require fresh tissue samples and are time consuming. Finally, the effective first-line therapy for ß-human chorionic gonadotrophin-producing high-risk gestational as well as non-gestational trophoblastic tumors is combination chemotherapy (the EMA/CO regimen). Therefore, treatment should be commenced when a potential diagnosis of metastatic trophoblastic tumor is being considered.

Monoclonal gammopathy of undetermined significance with amyloid deposition in the lung and non-amyloid eosinophilic deposition in the brain: a case report.

Background. Monoclonal gammopathy of undetermined significance (MGUS) is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER) after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH) included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic), incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP) as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT) revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), rheumatoid factor (RF), cryoglobulin, and antiglomerular basement membrane (anti-GBM) antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs) but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always necessary. Further research is needed in order to better define the optimal treatment and management strategies of MGUS and its complications.

Pathophysiology of cell phone radiation: oxidative stress and carcinogenesis with focus on male reproductive system.

Hazardous health effects stemming from exposure to radiofrequency electromagnetic waves (RF-EMW) emitted from cell phones have been reported in the literature. However, the cellular target of RF-EMW is still controversial. This review identifies the plasma membrane as a target of RF-EMW. In addition, the effects of RF-EMW on plasma membrane structures (i.e. NADH oxidase, phosphatidylserine, ornithine decarboxylase) and voltage-gated calcium channels are discussed. We explore the disturbance in reactive oxygen species (ROS) metabolism caused by RF-EMW and delineate NADH oxidase mediated ROS formation as playing a central role in oxidative stress (OS) due to cell phone radiation (with a focus on the male reproductive system). This review also addresses: 1) the controversial effects of RF-EMW on mammalian cells and sperm DNA as well as its effect on apoptosis, 2) epidemiological, in vivo animal and in vitro studies on the effect of RF-EMW on male reproductive system, and 3) finally, exposure assessment and dosimetry by computational biomodeling.

Cell phones: modern man's nemesis?

Over the past decade, the use of mobile phones has increased significantly. However, with every technological development comes some element of health concern, and cell phones are no exception. Recently, various studies have highlighted the negative effects of cell phone exposure on human health, and concerns about possible hazards related to cell phone exposure have been growing. This is a comprehensive, up-to-the-minute overview of the effects of cell phone exposure on human health. The types of cell phones and cell phone technologies currently used in the world are discussed in an attempt to improve the understanding of the technical aspects, including the effect of cell phone exposure on the cardiovascular system, sleep and cognitive function, as well as localized and general adverse effects, genotoxicity potential, neurohormonal secretion and tumour induction. The proposed mechanisms by which cell phones adversely affect various aspects of human health, and male fertility in particular, are explained, and the emerging molecular techniques and approaches for elucidating the effects of mobile phone radiation on cellular physiology using high-throughput screening techniques, such as metabolomics and microarrays, are discussed. A novel study is described, which is looking at changes in semen parameters, oxidative stress markers and sperm DNA damage in semen samples exposed in vitro to cell phone radiation.

Lifestyle and testicular dysfunction: a brief update.

The incidence of testicular cancer, cryptorchidism and defective spermatogenesis is increasing probably due to environmental and lifestyle-related factors. The aim of this review is to briefly describe and comment on the principal lifestyle factors. The recent findings that the electromagnetic waves following the use of the cell phone and the prolonged exposure to the noise stress cause relevant testicular dysfunction in man or animals reinforce the hypothesis of the importance of lifestyle-related factors.