The Effect of Daily Methylsulfonylmethane (MSM) Consumption on High-Density Lipoprotein Cholesterol in Healthy Overweight and Obese Adults: A Randomized Controlled Trial.

Interventions to decrease inflammation and improve metabolic function hold promise for the prevention of obesity-related diseases. Methylsulfonylmethane (MSM) is a naturally occurring compound that demonstrates antioxidant and anti-inflammatory effects. Improvements in measures of metabolic health have been observed in mouse models of obesity and diabetes following MSM treatment. However, the effects of MSM on obesity-related diseases in humans have not been investigated. Therefore, the purpose of this investigation was to determine whether MSM supplementation improves cardiometabolic health, and markers of inflammation and oxidative status. A randomized, double-blind, placebo-controlled design was utilized with a total of 22 overweight or obese adults completing the study. Participants received either a placebo (white rice flour) or 3 g MSM daily for 16 weeks. Measurements occurred at baseline and after 4, 8, and 16 weeks. Outcome measures included fasting glucose, insulin, blood lipids, blood pressure, body composition, metabolic rate, and markers of inflammation and oxidative status. The primary finding of this work shows that high-density lipoprotein cholesterol was elevated at 8 and 16 weeks of daily MSM consumption compared to baseline, (p = 0.008, p = 0.013). Our findings indicate that MSM supplementation may improve the cholesterol profile by resulting in higher levels of high-density lipoprotein cholesterol.

A Lin28 homologue reprograms differentiated cells to stem cells in the moss Physcomitrella patens.

Both land plants and metazoa have the capacity to reprogram differentiated cells to stem cells. Here we show that the moss Physcomitrella patens Cold-Shock Domain Protein 1 (PpCSP1) regulates reprogramming of differentiated leaf cells to chloronema apical stem cells and shares conserved domains with the induced pluripotent stem cell factor Lin28 in mammals. PpCSP1 accumulates in the reprogramming cells and is maintained throughout the reprogramming process and in the resultant stem cells. Expression of PpCSP1 is negatively regulated by its 3'-untranslated region (3'-UTR). Removal of the 3'-UTR stabilizes PpCSP1 transcripts, results in accumulation of PpCSP1 protein and enhances reprogramming. A quadruple deletion mutant of PpCSP1 and three closely related PpCSP genes exhibits attenuated reprogramming indicating that the PpCSP genes function redundantly in cellular reprogramming. Taken together, these data demonstrate a positive role of PpCSP1 in reprogramming, which is similar to the function of mammalian Lin28.

Digital gene expression profiling by 5'-end sequencing of cDNAs during reprogramming in the moss Physcomitrella patens.

Stem cells self-renew and repeatedly produce differentiated cells during development and growth. The differentiated cells can be converted into stem cells in some metazoans and land plants with appropriate treatments. After leaves of the moss Physcomitrella patens are excised, leaf cells reenter the cell cycle and commence tip growth, which is characteristic of stem cells called chloronema apical cells. To understand the underlying molecular mechanisms, a digital gene expression profiling method using mRNA 5'-end tags (5'-DGE) was established. The 5'-DGE method produced reproducible data with a dynamic range of four orders that correlated well with qRT-PCR measurements. After the excision of leaves, the expression levels of 11% of the transcripts changed significantly within 6 h. Genes involved in stress responses and proteolysis were induced and those involved in metabolism, including photosynthesis, were reduced. The later processes of reprogramming involved photosynthesis recovery and higher macromolecule biosynthesis, including of RNA and proteins. Auxin and cytokinin signaling pathways, which are activated during stem cell formation via callus in flowering plants, are also activated during reprogramming in P. patens, although no exogenous phytohormone is applied in the moss system, suggesting that an intrinsic phytohormone regulatory system may be used in the moss.

Adenoid cystic breast carcinoma: is axillary staging necessary in all cases? Results from the California Cancer Registry.

Adenoid cystic carcinoma (ACC) is an uncommon type of breast cancer. There are limited data about its epidemiology, tumor characteristics, and outcomes. Using a large, population-based data base, this study aimed to identify specific characteristics of patients with adenoid cystic breast cancer, investigate its natural history, and determine its long-term prognosis. The California Cancer Registry, a population-based registry, was reviewed from the years 1988 to 2006. The data were analyzed with relation to patient age, tumor size and stage, and overall survival. Relative cumulative actuarial survival was determined using the Berkson-Gage life table method. A total of 244 cases of invasive adenoid cystic cancer were identified in women during this time period. The patients' median age was 61.9 years. Most cases were diagnosed in non-Hispanic White women (82%, n = 200), followed by African American (6%, n = 15), Asian/Pacific-Islander (5.7%, n = 14) and Hispanic women (4.4%, n = 12). The remainder of the patients was of unknown or other ethnicity. Tumors were between 1 and 140 mm in size. At the time of diagnosis, 92% (n = 225) of patients had localized disease, 5% (n = 12) of patients had regional disease, and even fewer (n = 7) had either distant or unknown staged disease. Lymph node involvement was not present in any tumors smaller than 1.4 cm. The relative cumulative survival of patients with adenoid cystic breast carcinoma was 95.6% at 5 years and 94.9% at 10 years. ACC of the breast is a rare disease with an overall good prognosis. Knowing that this cancer usually presents as localized disease, with lymph node involvement seen only with larger tumors, can help clinicians plan the operative management of these tumors.

Fluorescence laparoscopy imaging of pancreatic tumor progression in an orthotopic mouse model.

BACKGROUND: The use of fluorescent proteins to label tumors is revolutionizing cancer research, enabling imaging of both primary and metastatic lesions, which is important for diagnosis, staging, and therapy. This report describes the use of fluorescence laparoscopy to image green fluorescent protein (GFP)-expressing tumors in an orthotopic mouse model of human pancreatic cancer. METHODS: The orthotopic mouse model of human pancreatic cancer was established by injecting GFP-expressing MiaPaCa-2 human pancreatic cancer cells into the pancreas of 6-week-old female athymic mice. On postoperative day 14, diagnostic laparoscopy using both white and fluorescent light was performed. A standard laparoscopic system was modified by placing a 480-nm short-pass excitation filter between the light cable and the laparoscope in addition to using a 2-mm-thick emission filter. A camera was used that allowed variable exposure time and gain setting. For mouse laparoscopy, a 3-mm 0° laparoscope was used. The mouse's abdomen was gently insufflated to 2 mm Hg via a 22-gauge angiocatheter. After laparoscopy, the animals were sacrificed, and the tumors were collected and processed for histologic review. The experiments were performed in triplicate. RESULTS: Fluorescence laparoscopy enabled rapid imaging of the brightly fluorescent tumor in the pancreatic body. Use of the proper filters enabled simultaneous visualization of the tumor and the surrounding structures with minimal autofluorescence. Fluorescence laparoscopy thus allowed exact localization of the tumor, eliminating the need to switch back and forth between white and fluorescence lighting, under which the background usually is so darkened that it is difficult to maintain spatial orientation. CONCLUSION: The use of fluorescence laparoscopy permits the facile, real-time imaging and localization of tumors labeled with fluorescent proteins. The results described in this report should have important clinical potential.

Clinical experience with a multifunctional, flexible surgery system for endolumenal, single-port, and NOTES procedures.

BACKGROUND: Single-port and incisionless surgical approaches hold the promise of fewer complications, reduced pain, faster recovery, and improved cosmesis compared with traditional open or laparoscopic approaches. The ability to select an access approach (i.e., endolumenal, single-port, transvaginal, or transgastric) with one platform may be important to optimization of individual patient results. The authors report their results using these four separate surgical approaches tailored to three different therapeutic procedures, all with the use of a single flexible platform, the Incisionless Operating Platform (IOP). METHODS: After institutional review board approval, the IOP was used to perform nine cholecystectomies via transvaginal (TV) (n=4), transgastric (TG) (n=4), and single-port transumbilical (TU) (n=1) access. Two appendectomies were performed via TG access. Endolumenal access was used for 18 gastric pouch and stoma reductions after Roux-en-Y gastric bypass. The TG and TV procedures involved the use of one to three trocars. The recorded data included safety, procedural success, operative time, patient pain assessment (on a 0-10 scale) at discharge, and length of hospital stay. RESULTS: Procedural success was achieved for 16 of 18 endolumenal procedures, 1 of 1 single-port procedure, and 10 of 10 NOTES procedures. For 5 of 10 NOTES procedures, only one small trocar was required. The mean operative times were 79 min for pouch with stoma reduction, 171 min for cholecystectomy, and 274 min for appendectomy. Of 29 patients, 27 were discharged in 24 h or less. The average pain scores were 0.44 for pouch with stoma reduction, 1.3 for cholecystectomy, and 2.5 for appendectomy. No significant complications occurred. The ergonomics of IOP allowed the surgeon to interface with the system using an endoscopic or laparoscopic orientation. CONCLUSION: Availability of a multifunctional, flexible surgery platform provides a choice of a single-port or incisionless surgical approach with the potential to reduce complications, pain, and recovery time while improving cosmesis.

Robotic single-incision transabdominal and transvaginal surgery: initial experience with intersecting robotic arms.

BACKGROUND: Single-incision laparoscopic and natural orifice translumenal endoscopic surgery (NOTES) are technically challenging methods. Robotics might have the potential to overcome such hurdles with computer technology. METHODS: The da Vinci Standard and S System (Intuitive, Sunnyvale, USA) were used in human cadavers and pigs to perform single-incision transabdominal and transvaginal surgery. Robotic arms were crossed and control-switched to achieve intuitive control. RESULTS: It was possible to perform robotic single-incision laparoscopy in the typical, intuitive fashion. Transvaginal set-up, including docking of the system and introduction of instruments into the abdominal cavity, was possible but no useful manipulation could be performed. CONCLUSIONS: While robotic NOTES with the da Vinci surgical system was not successful, robotic single-incision surgery is feasible using the above set-up. This new approach seems to offer the advantages of single-incision surgery while maintaining the intuitive control of robotic surgery. Clinical application appears justified.

Incisionless revision of post-Roux-en-Y bypass stomal and pouch dilation: multicenter registry results.

BACKGROUND: Surgical revision for weight regain after Roux-en-Y gastric bypass (RYGB) has been tempered by the high complication rates associated with standard approaches. Endoluminal revision of stoma and pouch dilation should intuitively confer a better risk profile. However, questions of clinical safety, durability, and weight loss need to be answered. We report our multicenter intraoperative experience and postoperative follow-up to date using the Incisionless Operating Platform for this patient subset. METHODS: The patients who had regained significant weight >or=2 years after RYGB after losing >or=50% of excess body weight after RYGB were endoscopically screened for stomal and/or pouch dilation. Qualified patients underwent incisionless revision using the Incisionless Operating Platform to reduce the stoma and pouch size by placing anchors to create tissue plications. Data on the safety, intraoperative performance, postoperative weight loss, and anchor durability were recorded to date as a part of 2 years of postoperative follow-up. RESULTS: A total of 116 consecutive patients were prospectively studied. Anchors were successfully placed in 112 (97%) of 116 patients, with an average intraoperative stoma diameter and pouch length reduction of 50% and 44%, respectively. The operating room time averaged 87 minutes. No significant complications occurred. At 6 months after the procedure (n = 96), an average of 32% of weight regain that had occurred after RYGB had been lost. The percentage of excess weight loss averaged 18%. The 12-month esophagogastroduodenoscopy results confirmed the presence of the anchors and durable tissue folds. CONCLUSIONS: Incisionless revision of stoma and pouch dilation using the Incisionless Operating Platform can be performed safely. The data to date have demonstrated mild-to-moderate weight loss, and the early 12-month endoscopic images have confirmed anchor durability. Patients were actively followed up to document the long-term durability of this intervention in the entire patient subset.

Early ambulation after percutaneous femoral access with use of closure devices and hemostatic agents.

BACKGROUND: Patient satisfaction after percutaneous endovascular procedures is significantly influenced by the amount of time to ambulation postprocedure. The purpose of this study was to assess the complication rates of early ambulation after use of closure devices or topical hemostatic agents for femoral access sites for endovascular procedures. METHODS: A retrospective review was performed of all patients who underwent an endovascular procedure from a femoral access site between January 2004 and March 2008. The access site was closed with an Angio-Seal, StarClose, or D-Stat Dry with pressure. Patients ambulated 2 hr postprocedure when a closure device was used and 4 hr postprocedure when a D-Stat pad was applied. Access-site bleeding complications were assessed. Sheath size, closure method, patient characteristics, and antiplatelet status were analyzed. RESULTS: A total of 245 patients with a mean age of 70 years were identified. Of these, 154 (63%) patients were treated with a D-Stat pad with pressure, Angio-Seal was used on 83 (34%), and StarClose was used on eight (3%). The overall complication rate was 5.7%. Complications increased with increasing age (p = 0.003) and use of StarClose (p = 0.0001). The D-Stat pad was associated with a decreased complication rate (p = 0.03). Sheath size did not influence the incidence of bleeding. There was no significant increase in complications in patients taking an antiplatelet agent. CONCLUSION: With a protocol using closure devices and hemostatic agents, early ambulation after percutaneous femoral access can be achieved safely with an acceptable complication rate in patients with peripheral vascular disease.

Supra-pubic single incision cholecystectomy.

INTRODUCTION: Surgery is moving towards less invasive and cosmetically superior approaches such as single incision laparoscopy (SIL). While trans-umbilical SIL is gaining popularity, incisions may lead to post-operative deformations of the umbilicus and the possibility of an increased rate of incisional hernias. Access within the pubic hairline allows preservation of the umbilicus and results in a scar which is concealed within the pubic hair. METHODS: Supra-pubic single incision cholecystectomy was performed in a 30-year-old patient with symptomatic gallstones. A 2.5-cm transverse incision was placed within the pubic hairline and a subcutaneous tunnel was formed. Three 5-mm ports were introduced into the tunnel and perforated the anterior rectus sheath superior to the skin incision. The surgical procedure was then undertaken with conventional laparoscopic instrumentation. The adjacent 5-mm incisions were merged for gallbladder removal. The entry site was closed under direct vision. RESULTS: The above procedure was technically feasible and without complication. Operative time was 45 min, and the patient was discharged 5 h post-operatively. CONCLUSIONS: Supra-pubic single incision laparoscopic cholecystectomy may offer a more cosmetically appealing result than standard umbilical access. The operation can be performed by surgeons skilled in single incision techniques with good result.

Attaining negative margins in breast-conservation operations: is there a consensus among breast surgeons?

BACKGROUND: The purpose of this survey was to ascertain the most common surgical practices for attaining negative (tumor-free) surgical margins in patients desiring breast-conservation treatment for breast cancer to see if a consensus exists for optimal treatment of patients. STUDY DESIGN: We sent a survey to 1,000 surgeons interested in the treatment of breast cancer. Three hundred eighty-one surgeons responded to this survey and 351 were used for the analysis (response rate of 38%). RESULTS: Answers showed a large variety in clinical practices among breast surgeons across the country. There was little intraoperative margin analysis; only 48% of surgeons examine the margins grossly with a pathologist and even fewer used frozen sections or imprint cytology. Decisions to reexcise specific margins varied greatly. For example, 57% of surgeons would never reexcise for a positive deep margin, but 53% would always reexcise for a positive anterior margin. Most importantly, there was a large range in answers about acceptable margins with ductal carcinoma in situ and invasive carcinoma. Fifteen percent of surgeons would accept any negative margin, 28% would accept a 1-mm negative margin, 50% would accept a 2-mm negative margin, 12% would accept a 5-mm negative margin, and 3% would accept a 10-mm negative margin. CONCLUSIONS: Results of this survey highlight the wide variety of practice patterns in the US for handling surgical margins in breast-conservation treatment. This issue remains controversial, with no prevailing standard of care. Consequently, additional study is needed in the modern era of multimodality treatment to examine the minimal amount of surgical treatment necessary, in conjunction with chemotherapy and radiation, to attain adequate local control rates in breast-conservation treatment.

Transrectal endoscopic retrorectal access (TERA): a novel NOTES approach to the peritoneal cavity.

BACKGROUND: As the field of natural orifice translumenal endoscopic surgery (NOTES) expands, new access sites are being investigated. One access site to the peritoneal cavity, which has not been the subject of much investigation, is transrectal access. The aim of this article is to describe a new method to peritoneal access: transrectal endoscopic retrorectal access (TERA). MATERIALS AND METHODS: Three pigs were placed in the supine position under general anesthesia, and an umbilical port was placed for the pneumoperitoneum, as well as visualization of the pelvic dissection and access. A rectotomy was made under direct vision above the dentate line posteriorly. The flexible endoscope was introduced into the retrorectal space, balloon dilation was used to open and dissect the retrorectal plane, and the peritoneal cavity was entered with a needle knife. After peritoneal exploration, the endoscope was withdrawn and the rectotomy was closed under direct vision. RESULTS: Each of the 3 cases was successful with entry into the peritoneal cavity to the right of the sacral promontory. Direct visualization allowed the avoidance of injury to the ureter, vessels, and nervous structures of the pelvis. The flexible endoscope allowed an easy direct visualization of the upper abdominal organs. In addition, retroflexion allowed a view of the pelvic organs. Mean operative time was 40 minutes. CONCLUSIONS: TERA is a novel access route to the peritoneal cavity that can be performed by using readily available instrumentation. When performed under direct view, injury to the adjacent structures can be avoided while obtaining access. Unresolved issues include sterility of the procedure and reproducibility, and future survival studies will delineate long-term safety.

Treatment of chylothorax by robotic thoracic duct ligation.

This is the first report describing the use of robotic technology for the treatment of chylothorax. We present a 22-year-old with mixed embryonal cell and seminoma germ cell cancer refractory to medical and surgical treatment. The patient had rising markers and a growing left lower lung lobe metastasis. After left lower lobectomy, left-sided chylothorax developed. Conservative management failed, and a robotic right-sided thoracic duct ligation was performed. Other treatment options are reviewed.