Werner Syndrome (WRN) is an autosomal recessive disorder with an elevated risk of cancer resulting from mutations in the WRN DNA helicase/exonuclease gene. Lymphoblastoid cells (LCLs) from WRN patients have previously been shown to have increased toxicity after exposure to 4‐nitroquinoline‐N‐oxide (4NQO) and to camptothecin. Exposure to camptothecin leads to trapping of DNA topoisomerase I molecules onto the DNA, whereas 4NQO may induce diverse forms of chromatin damage. To elucidate the nature of the chromatin lesion(s) to which WRN deficient cells are sensitive, we exposed LCLs to drugs with a spectrum of biochemically defined mechanisms. We found that WRN deficient LCLs show elevated sensitivity to melphalan, chlorambucil, mitomycin C, and cis‐platinum(II)diammine dichloride, but not to trans‐platinum(II)diammine dichloride, etoposide, berenil, daunomycin, adriamycin, mitoxantrone, and echinomycin. The drugs to which WRN deficient LCLs are more sensitive all induce apoptosis in S phase and all share the formation of DNA‐interstrand cross‐links as a common biochemical lesion. We hypothesize that cells deficient for WRN function may have a reduced capacity to remove DNA‐interstrand cross‐links, which may lead to apoptosis, increased chromosome aberrations, and cancer in WRN patients.

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Transvaginal placement of synthetic mesh to repair large porcine hernia using NOTES technology appears to be a feasible alternative to traditional techniques.

The foundation for natural orifice transluminal endoscopic surgery (NOTES) is to access the peritoneal and other body cavities through the wall of the alimentary tract via natural orifices, with the goal of performing procedures within the peritoneum and other cavities, without the need to make incisions in the abdominal wall. We have made great progress in the field of NOTES since the publication of the White Paper in 2006. There are still major fundamental goals as outlined by the Society of American Gastrointestinal and Endoscopic Surgeons/American Society for Gastrointestinal Endoscopy joint committee that need to be evaluated and answered before NOTES is ready for widespread clinical use. These include prevention of infection, instrument development, creation of a multitasking platform, and the ability to recognize and treat intraperitoneal complications such as hemorrhage and other physiological adverse events. In response to this need, recent abstracts and papers have focused on the management of intraoperative complications. The next phase is to focus on controlled prospective multicenter clinical trials that compare defined NOTES procedure to standard laparoscopy. The goal is to produce reliable and convincing data for the United States Food and Drug Administration, insurance companies, the physician community and the general public. At the present time, we still have many important milestones that still need to be met. Most investigators agree that a hybrid technique and not a pure NOTES practice should be advocated until devices can meet the current and new challenges in this field.

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Placement of fully covered metal stents is feasible. The use of small pigs with a thin small bowel wall in combination with relatively large stents was most likely the reason for complications found in all stented animals. Further studies of GJ leaks using these stents will require larger pigs or a different species.

NOTES cholecystectomy without laparoscopic support is feasible but challenging using prototype flexible endoscopic devices. A prototype clip applier was effective in controlling the cystic duct. Further improvements in instrument design to ensure precision and safety are needed before flexible devices should be used for pure NOTES procedures in humans.

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