Mechanical bowel preparation and antimicrobial prophylaxis in elective colorectal surgery in Switzerland—a survey

Background: The aim of this study was to assess the use of mechanical bowel preparation (MBP) and antimicrobial prophylaxis in elective colorectal surgery in Switzerland. Methods: Ninety-eight heads of surgical departments in Switzerland and 42 visceral surgeons in private practice were asked to answer an 18-item questionnaire in October 2008 about arguments in favor of or against MBP. The participants also indicated whether they use MBP and antimicrobial prophylaxis in colorectal surgery, and if so, what agents were used. Of the participants, 117/140 (83%) responded. Additional data were collected pertaining to the respondents' experience and work situation. Results: MBP was used significantly more often for rectal surgery than for left colonic resections (83% vs. 53%; p < 0.001) and more often for left than for right colonic resections (53% vs. 43%; p = 0.001), regardless of the open or laparoscopic approach. Younger surgeons and surgeons with a higher case load in colorectal surgery used MBP significantly less frequently in open right colonic resections. For MBP, cathartics were used in 90% of patients, and enemas were used in 10% of patients. Of the respondents, 37% considered MBP to be useful, even very useful. Based on the literature, because of introduction of fast-track protocols or for considerations of patient comfort, 86% of the respondents had changed the bowel preparation regime during the last 10years in terms of a reduction of the quantity of cathartics or restricted the indications for MBP. Antimicrobial prophylaxis was used by 100% of the respondents, 88% used a single prophylactic dose only, while 70% administered the antibiotics 30-59min before the incision. Most of the surgeons used second-generation cephalosporins in combination with metronidazole, and 24% changed the antibiotic agent or reduced the duration of administration of antibiotics during the last 10years. Conclusions: MBP is often used in open and laparoscopic rectal surgery, but not in right colonic resections. Scientific evidence regarding MBP has yielded a rethinking about rigorous bowel preparation regimes. As of now, surgeons in Switzerland are not yet unanimously ready to abandon MBP in elective colorectal surgery. In Switzerland, surgeons are influenced by the benefit of antimicrobial prophylaxis in colorectal surger

Mitochondrial DNA Content in Human Omental Adipose Tissue

Background: Impairment of mitochondrial function plays an important role in obesity and the development of insulin resistance. The aim of this project was to investigate the mitochondrial DNA copy number in human omental adipose tissue with respect to obesity. Methods: The mitochondrial DNA (mtDNA) content per single adipocyte derived from abdominal omental adipose tissue was determined by quantitative RT-PCR in a group of 75 patients, consisting of obese and morbidly obese subjects, as well as non-obese controls. Additionally, basal metabolic rate and fat oxidation rate were recorded and expressed as total values or per kilogram fat mass. Results: MtDNA content is associated with obesity. Higher body mass index (BMI) resulted in a significantly elevated mtDNA count (ratio = 1.56; p = 0.0331) comparing non-obese (BMI < 30) to obese volunteers (BMI ≥ 30). The mtDNA count per cell was not correlated with age or gender. Diabetic patients showed a trend toward reduced mtDNA content. A seasonal change in mtDNA copy number could not be identified. In addition, a substudy investigating the basal metabolic rate and the fasting fat oxidation did not reveal any associations to the mtDNA count. Conclusions: The mtDNA content per cell of omental adipose tissue did not correlate with various clinical parameters but tended to be reduced in patients with diabetes, which may partly explain the impairment of mitochondrial function observed in insulin resistance. Furthermore, the mtDNA content was significantly increased in patients suffering from obesity (BMI above 30). This might reflect a compensatory response to the development of obesity, which is associated with impairment of mitochondrial functio

Systematic identification of novel cancer genes through analysis of deep shRNA perturbation screens.

Systematic perturbation screens provide comprehensive resources for the elucidation of cancer driver genes. The perturbation of many genes in relatively few cell lines in such functional screens necessitates the development of specialized computational tools with sufficient statistical power. Here we developed APSiC (Analysis of Perturbation Screens for identifying novel Cancer genes) to identify genetic drivers and effectors in perturbation screens even with few samples. Applying APSiC to the shRNA screen Project DRIVE, APSiC identified well-known and novel putative mutational and amplified cancer genes across all cancer types and in specific cancer types. Additionally, APSiC discovered tumor-promoting and tumor-suppressive effectors, respectively, for individual cancer types, including genes involved in cell cycle control, Wnt/β-catenin and hippo signalling pathways. We functionally demonstrated that LRRC4B, a putative novel tumor-suppressive effector, suppresses proliferation by delaying cell cycle and modulates apoptosis in breast cancer. We demonstrate APSiC is a robust statistical framework for discovery of novel cancer genes through analysis of large-scale perturbation screens. The analysis of DRIVE using APSiC is provided as a web portal and represents a valuable resource for the discovery of novel cancer genes

Genomic analysis of focal nodular hyperplasia with associated hepatocellular carcinoma unveils its malignant potential: a case report.

Background Focal nodular hyperplasia (FNH) is typically considered a benign tumor of the liver without malignant potential. The co-occurrence of FNH and hepatocellular carcinoma (HCC) has been reported in rare cases. In this study we sought to investigate the clonal relationship between these lesions in a patient with FNH-HCC co-occurrence. Methods A 74-year-old female patient underwent liver tumor resection. The resected nodule was subjected to histologic analyses using hematoxylin and eosin stain and immunohistochemistry. DNA extracted from microdissected FNH and HCC regions was subjected to whole exome sequencing. Clonality analysis were performed using PyClone. Results Histologic analysis reveals that the nodule consists of an FNH and two adjoining HCC components with distinct histopathological features. Immunophenotypic characterization and genomic analyses suggest that the FNH is clonally related to the HCC components, and is composed of multiple clones at diagnosis, that are likely to have progressed to HCC through clonal selection and/or the acquisition of additional genetic events. Conclusion To the best of our knowledge, our work is the first study showing a clonal relationship between FNH and HCC. We show that FNH may possess the capability to undergo malignant transformation and to progress to HCC in very rare cases

Standardizing Patient-Derived Organoid Generation Workflow to Avoid Microbial Contamination From Colorectal Cancer Tissues.

The use of patient-derived organoids (PDO) as a valuable alternative to in vivo models significantly increased over the last years in cancer research. The ability of PDOs to genetically resemble tumor heterogeneity makes them a powerful tool for personalized drug screening. Despite the extensive optimization of protocols for the generation of PDOs from colorectal tissue, there is still a lack of standardization of tissue handling prior to processing, leading to microbial contamination of the organoid culture. Here, using a cohort of 16 patients diagnosed with colorectal carcinoma (CRC), we aimed to test the efficacy of phosphate-buffered saline (PBS), penicillin/streptomycin (P/S), and Primocin, alone or in combination, in preventing organoid cultures contamination when used in washing steps prior to tissue processing. Each CRC tissue was divided into 5 tissue pieces, and treated with each different washing solution, or none. After the washing steps, all samples were processed for organoid generation following the same standard protocol. We detected contamination in 62.5% of the non-washed samples, while the use of PBS or P/S-containing PBS reduced the contamination rate to 50% and 25%, respectively. Notably, none of the organoid cultures washed with PBS/Primocin-containing solution were contaminated. Interestingly, addition of P/S to the washing solution reduced the percentage of living cells compared to Primocin. Taken together, our results demonstrate that, prior to tissue processing, adding Primocin to the tissue washing solution is able to eliminate the risk of microbial contamination in PDO cultures, and that the use of P/S negatively impacts organoids growth. We believe that our easy-to-apply protocol might help increase the success rate of organoid generation from CRC patients

Transcriptional Enhancer Factor Domain Family member 4 Exerts an Oncogenic Role in Hepatocellular Carcinoma by Hippo-Independent Regulation of Heat Shock Protein 70 Family Members.

Transcriptional enhancer factor domain family member 4 (TEAD4) is a downstream effector of the conserved Hippo signaling pathway, regulating the expression of genes involved in cell proliferation and differentiation. It is up-regulated in several cancer types and is associated with metastasis and poor prognosis. However, its role in hepatocellular carcinoma (HCC) remains largely unexplored. Using data from The Cancer Genome Atlas, we found that TEAD4 was overexpressed in HCC and was associated with aggressive HCC features and worse outcome. Overexpression of TEAD4 significantly increased proliferation and migration rates in HCC cells in vitro as well as tumor growth in vivo. Additionally, RNA sequencing analysis of TEAD4-overexpressing HCC cells demonstrated that TEAD4 overexpression was associated with the up-regulation of genes involved in epithelial-to-mesenchymal transition, proliferation, and protein-folding pathways. Among the most up-regulated genes following TEAD4 overexpression were the 70-kDa heat shock protein (HSP70) family members HSPA6 and HSPA1A. Chromatin immunoprecipitation-quantitative real-time polymerase chain reaction experiments demonstrated that TEAD4 regulates HSPA6 and HSPA1A expression by directly binding to their promoter and enhancer regions. The pharmacologic inhibition of HSP70 expression in TEAD4-overexpressing cells reduced the effect of TEAD4 on cell proliferation. Finally, by overexpressing TEAD4 in yes-associated protein (YAP)/transcriptional coactivator with PDZ binding motif (TAZ)-knockdown HCC cells, we showed that the effect of TEAD4 on cell proliferation and its regulation of HSP70 expression does not require YAP and TAZ, the main effectors of the Hippo signaling pathway. Conclusion: A novel Hippo-independent mechanism for TEAD4 promotes cell proliferation and tumor growth in HCC by directly regulating HSP70 family members

Drain-Site Hernia Containing the Vermiform Appendix: Report of a Case

The herniated vermiform appendix has been described as content of every hernia orifice in the right lower quadrant. While the femoral and inguinal herniated vermiform appendix is frequent enough to result in an own designation, port-site or even drain-site hernias are less frequently described. We report the case of a 62-year-old woman who presented with right lower quadrant pain seven years after Roux-en-Y Cystojejunostomy for a pancreatic cyst. CT scan showed herniation of the vermiform appendix through a former drain-site. A diagnostic laparoscopy with appendectomy and direct closure of the abdominal wall defect combined with mesh reinforcement was performed. Despite the decreasing use of intraperitoneal drains over the recent years, a multitude of patients had intraperitoneal drainage in former times. These patients face nowadays the risk of drain-site hernias with sometimes even unexpected structures inside

Giant Symptomatic Rectal Mucocele following Subtotal Colectomy

Introduction: Rectal mucoceles rarely occur and only a few cases are described in the literature. They usually appear after subtotal colectomy or Hartmann procedure originating from persisting rectal mucus production and simultaneous stenosis of the anal canal. Case Presentation: A 74-year-old female patient presented with the feeling of an abdominal growing mass. Complex medical history included a subtotal colectomy with an end ileostomy and a mucous fistula at the descending colon due to Crohn disease at the age of 16 years. MRI showed a massive dilatation of the remaining colon and the rectum. Endoscopy failed due to complete anal stenosis and stenosis of the descending colon at the stoma site. A total proctocolectomy was performed. The pathology report showed a dilated rectum and sigma with large amounts of partly calcified mucus. There was no evidence of dysplasia, malignancy, or Crohn manifestation in the completely obliterated proximal colon and the anus. Conclusion: Our case report underlines the importance of active endoscopic surveillance of the remaining colon and rectum in patients with diverting stomas and inflammatory bowel disease in order to detect stenosis. If endoscopic control is not possible due to obliteration, surgical therapy must be discussed due to the risk of developing cancer

Primitive neuroectodermal tumor of the kidney in an adult: a case report

INTRODUCTION: Primitive neuroectodermal tumors (PNETs) occur predominantly in childhood preferentially in the soft tissues of the lower extremity and the paraspinal region. We present here a rare case of a PNET of the kidney in an adult. CASE PRESENTATION: A tumor adjacent to the right kidney was detected by ultrasound coincidentally at a routine check-up in a 46-year-old woman with irritable bowel syndrome in her medical history. The patient had no clinical signs. Contrast-enhanced computerized tomography scan of the abdomen demonstrated a highly vascularized renal tumor. A retroperitonealectomy with en-bloc resection of the kidney was performed, and histopathological work-up showed a primitive neuroectodermal tumor of the kidney with the characteristic translocation t(11;22)(q24;q12). CONCLUSION: This tumor entity must be accurately distinguished from other renal neoplasms because of the prognostic and therapeutic impact