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Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered may-tansine site of tubulin. Using this assay, we have determined the dissociation constants of known may-ansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on β-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Background: Lower gastrointestinal bleeding represents 20 % of all gastrointestinal bleedings. Interventional radiology has transformed the treatment of this pathology, but the long-term outcome after selective embolization has been poorly evaluated. The aim of this study is thus to evaluate the short-term and long-term outcomes after selective embolization for colonic bleeding. Methods: From November 1998 to December 2010, all acute colonic embolizations for hemorrhage were retrospectively reviewed and analyzed. The risk factors for post-embolization ischemia were also assessed. Results: Twenty-four patients underwent colonic embolization. There were 6 men and 18 women with a median age of 80 years (range, 42-94 years). The underlying etiologies included diverticular disease (41.9 %), post-polypectomy bleeding (16.7 %), malignancy (8.2 %), hemorrhoid (4.1 %), and angiodysplasia (4.1 %). In 23 patients, bleeding stopped (95.8 %) after selective embolization. One patient presented a recurrence of bleeding with hemorrhagic shock and required urgent hemorrhoidal ligature. Four patients required an emergent surgical procedure because of an ischemic event (16.7 %). One patient died of ileal ischemia (mortality, 4.1 %). The level of embolization and the length of hypoperfused colon after embolization were the only risk factors for emergent operation. Mean hospital stay was 18 days (range, 9-44 days). After a mean follow-up of 28.6 months (range, 4-108 months), no other ischemic events occurred. Conclusion: In our series, selective transarterial embolization for acute colonic bleeding was clinically effective with a 21 % risk of bowel ischemia. The level of embolization and the length of the hypoperfused colon after embolization should be taken into consideration for emergent operation. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted Roux-en-Y gastric bypass (RYGBP) is rapidly evolving as an important surgical approach in the bariatric field. However, the specific learning curve associated with this new approach remains poorly investigated. This study aimed to evaluate the learning curve for robot-assisted RYGBP. Methods: A series of 64 consecutive robot-assisted RYGBP procedures were performed between December 2008 and December 2010 by a single surgeon already experienced in advanced laparoscopic procedures but not in bariatric surgery. All data were collected prospectively in a database and reviewed retrospectively. The learning curve was evaluated using the cumulative sum (CUSUM) method. Results: Women comprised 76.6% and men 23.4% of this series. These patients had a mean age of 43 years and a mean body mass index (BMI) of 44.5 kg/m. The mean operative time (OT) was 238.1 min (range, 150-400 min). A total of six complications occurred (9.4%). The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 14 cases; mean OT, 288.9 min) and phase 2 (the subsequent cases; mean OT, 223.6 min), which represented the mastery phase, with a decrease in OT ( P = 0.0001). The two groups were similar in terms of gender, age, and BMI. The two phases did not differ in terms of complications or hospital stay. Conclusions: This series confirms previous study findings concerning the feasibility and the safety of robotic RYGBP even after a limited experience with laparoscopic RYGBP. The data reported in this article suggest that the learning phase for robot-assisted RYGBP can be achieved with 14 cases. [ABSTRACT FROM AUTHOR]

Background: Recent population survey has shown a preference for transumbilical laparoendoscopic single-site surgery (U-LESS) compared with natural orifice transluminal endoscopic surgery (NOTES) for cholecystectomy, assuming similar surgical risk. This study was designed to evaluate the perception and preference of women regarding conventional laparoscopy, U-LESS, and transvaginal NOTES (TV-NOTES) with particular interest to access perception. Methods: An anonymous questionnaire on laparoscopic, U-LESS, and TV-NOTES cholecystectomy, without regards to risks or advantages, was given to female medical/paramedical staff ( n = 100), patients ( n = 100), and the general population ( n = 100). Women participants (median age, 35 (range, 16-79) years) were queried about preference, perception of the different accesses, and personal informations. Of the respondents, 54% had children, 79% had stable relationships, and 96% were sexually active (vaginal intercourse). Results: With similar operative risk, 87% preferred U-LESS, 4% TV-NOTES and 8% laparoscopy. LESS/NOTES choice was influenced by a desire of improved cosmetics (82%) and lower pain (44%). 96% had worries regarding transvaginal access, among them: dyspareunia (68%), decreased sensibility during intercourse (43%), refuse of short-term sexual abstinence (40%), and infertility (23%). Transumbilical access evocated worries in 35%: umbilical pain (19%), postoperative umbilical sensibility (15%), and incisional hernia (11%). Postoperative intercourse abstinence after TV-NOTES evocated worries in 76% (defined as 3 weeks in survey): feel less attractive (40%), less feminine (32%), tension with their intimate (35%), lover non-acceptation (20%), possible abortion of new relationship (26%), and feel less comfortable socially (16%). Conclusions: The high acceptation rate for U-LESS approach compared with TV-NOTES may be related to fears regarding postoperative sexuality and fertility. The importance of temporary postoperative sexual abstinence (vaginal intercourse) is high and may be difficult to influence. Future research on TV-NOTES should focus on the access risk to be able to scientifically reassure our patients. For now, U-LESS seems to be favor compared with TV-NOTES for cholecystectomy in female patients. [ABSTRACT FROM AUTHOR]

Background: Although still under development, single-port access (SPA) approach may be of interest in patients prone to port-side incisional hernia, ensuring absence of increased fascial incision. This forms the basis for evaluating SPA for prosthetic ventral hernia repair. We report a new SPA technique of ventral hernia repair using working-channel endoscope, standard laparoscopic instruments, and 10-mm port. Methods: Prospective experience with SPA prosthetic repair of primary and incisional ventral hernia in 52 patients for 55 ventral hernias is presented. Median (range) patient age was 46 years (26-85 years), and BMI was 28 kg/m (20-38 kg/m). Mean fascial defect was 16.2 cm for primary hernia ( n = 23) and 48.3 cm for incisional hernia ( n = 32). Intraperitoneal composite mesh repair was achieved through single 10-mm flank port using working-channel endoscope. Meshes were fixed using absorbable tackers and transfascial stitches. Results: SPA repair of primary and incisional ventral hernia was completed in all cases without conversion to standard laparoscopy. Median (range) operative time was 54 min (39-95 min). Mesh size ranged from 118 to 500 cm. No intra- or postoperative complications were recorded, except two seromas. Median (range) hospital stay was 1 day (1-5 days). One patient presented prolonged postoperative pain on mesh fixation that resolved after 3 months. No recurrence or port-site incisional hernias have been recorded at median (range) follow-up of 16 months (3-28 months). Conclusions: SPA prosthetic repair of primary and incisional ventral hernia is easily feasible according to natural exposition by pneumoperitoneum and gravity. In the present series, SPA ventral hernia repair appears to be safe for experienced SPA surgeons. It may decrease parietal trauma and scarring in patients prone to incisional hernia. SPA repair may be associated with a decrease in rate of port-site incisional hernia compared with multiport laparoscopy, but this has to be verified by randomized trial with standard laparoscopic approach on long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Laparoendoscopic single-site surgery (LESS) and natural orifice translumenal endoscopic surgery (NOTES) are prospected as the future of minimally invasive surgery. While scarless surgery (NOTES and LESS) is gaining increasing popularity, perception of these approaches should be investigated. Methods: An anonymous questionnaire describing laparoscopy, LESS, and NOTES was given to medical staff ( n = 120), paramedical staff ( n = 100), surgical patients ( n = 100), and the general population ( n = 100). The survey participants (median age, 37 years; range, 18-81 years) were queried about their expectations for surgical treatment and their approach preference. Results: The first concern of the survey responders was the risk of surgical complications (92%). When asked about the respective importance of surgical safety, cure, and cosmetics, cure was placed first by 74%, safety by 33%, and cosmetics by 3%. These results were not influenced by sex, age, prior surgery or endoscopy, or education. When operative risk was similar, 90% of the participants preferred a scarless approach (75% preferred LESS and 15% preferred NOTES) to laparoscopy. The scarless approach preference was significantly higher among the younger participants (age <40 years; p = 0.026), whereas sex showed no influence. The LESS preference was significantly higher among patients and the general population (86%) than among medical (67%) and paramedical (70%) staffs ( p < 0.001). A decreasing trend of preference for LESS and NOTES was observed with increased procedural risks. Conclusion: Although cure and safety remain the main concern, the population has a favorable perception of scarless surgery, even in the case of increased procedural risk, with LESS favored over NOTES. Such a popular adoption of scarless surgery should warrant the promotion of further research, technological innovations, and the establishment of surgeon training to improve its safety. [ABSTRACT FROM AUTHOR]

Despite improvements in minimally invasive techniques over recent decades, kidney implantation into the iliac fossa has remained a domain of open surgery. However, it was hypothesized that it would be feasible to perform robotic transplant kidney implantation as a means of reducing surgical trauma. Two robotic kidney transplantations into the iliac fossa were attempted in human cadavers. In the first cadaver, a 5 cm incision was placed in the right lower abdomen, the peritoneum was mobilized in a cranial direction, the iliac vessels were identified, and the kidney placed in the pre-peritoneal space. The incision was sealed with a gel port through which the Vinci Surgical System was installed. In the second cadaver, a robotic kidney implantation with robotically sutured vascular and ureteric anastomoses was performed trans-abdominally. Open incision, identification, placement of gel port, and robotic docking were feasible. Robotic performance of vascular anastomosis was not possible in the first cadaver because of advanced decay and excess fat in the surgical field. Robotic kidney positioning was feasible and anastomoses were performed successfully in the second cadaver within 35, 25, and 20 min (arterial, venous, and ureteric, respectively). Robotic kidney transplantation seems feasible in human cadavers if tissue condition is suitable, but is very technically challenging. Because of the delicacy of anatomical structures, the cadaveric model with the risk of advanced decay and the absence of circulation sets limits on the exploration of this complex procedure. Hence, further research and animal work in this area is critical to improve understanding of the benefits and limitations of robotic kidney implantation. [ABSTRACT FROM AUTHOR]

Laparoscopic gastrojejunostomy allows effective palliation and rapid recovery for the patient with limited survival due to advanced pancreatic cancer presenting with gastric outlet obstruction. Transumbilical single-incision laparoscopic surgery (SILS) offers excellent cosmetic results and may be associated with decreased postoperative pain, reduced need for analgesia, and thus accelerated recovery. The authors report the first transumbilical single-incision laparoscopic intracorporeal anastomosis for gastrojejunostomy. Preliminary experience with transumbilical single-incision, intracorporeal anastomosis for gastrojejunostomy for a patient with gastric outlet obstruction caused by advanced pancreatic cancer is reported. Transumbilical single-incision laparoscopic intracorporeal anastomosis for gastrojejunostomy was performed with a linear endoscopic stapler using an omega loop. The operative time was 117 min. No intra- or postoperative complications were recorded. Transumbilical single-incision laparoscopic intracorporeal anastomoses are feasible using the endoscopic linear stapler. Transumbilical single-incision gastrojejunostomy for gastric outlet obstruction may improve cosmetic results and allow accelerated recovery for patients with limited survival. This anastomosis technique of single-incision laparoscopic surgery for other digestive tract procedures needs further evaluation. [ABSTRACT FROM AUTHOR]

Single port access (SPA) surgery is a rapidly evolving field as it combines some of the cosmetic advantage of the Natural Orifice Translumenal Endoscopic Surgery (NOTES) and allows performing surgical procedure with standard surgical instruments. We report in this paper a new technique of umbilical SPA right hemicolectomy with conventional surgical oncologic principle and technique of minimally invasive colectomy. Preliminary experience with umbilical SPA right hemicolectomy in a patient with degenerated ascending colon polyp. Umbilical SPA right hemicolectomy was feasible with conventional laparoscopic instruments. Carcinologic surgical principle can be respected using this technique as pathological specimen had sufficient surgical margins (>10 cm) and lymph nodes (33). Operative time was 158 min. No peroperative or postoperative complications were recorded. SPA right hemicolectomy is feasible and safe when performed by experienced laparoscopic surgeons. SPA right hemicolectomy may have the advantage over NOTES approach to offer the safety of laparoscopic colectomy especially for haemostasis and anastomosis. It has to be determined whether or not this approach would offer benefit to patients, except in cosmesis, compared to standard laparoscopic right hemicolectomy. [ABSTRACT FROM AUTHOR]

A number of surgical techniques for colorectal anastomosis have been described for laparoscopic left-sided colectomies. Due to the complexity of these procedures, open preparation of the proximal bowel for circular stapler anastomosis through a Pfannenstiel incision has become the gold standard. We report a new laparoscopic technique for totally intracorporeal colorectal circular anastomosis (TLCCA) using a circular stapler. Preliminary experience using TLCCA in three patients scheduled for laparoscopic left colectomies (two) and sigmoidectomy (one). Side-to-end colorectal anastomosis through TLCCA was feasible in all patients scheduled for preliminary experience. Median time from anvil insertion into abdominal cavity to anastomosis was 14 (11–17) minutes. No postoperative complications were recorded. Side-to-end anastomosis can be easily and safely performed using conventional circular stapler through TLCCA. TLCCA is performed using four laparoscopic ports without additional skin incision (except trocars incision) and allows the retrieval of surgical pieces through a specimen bag. [ABSTRACT FROM AUTHOR]

Anastomotic dehiscence is the most severe surgical complication after large bowel resection. This study was designed to assess the incidence, to observe the consequences, and to identify the risk factors associated with anastomotic leakage after colorectal surgery. All procedures involving anastomoses of the colon or the rectum, which were performed between November 2002 and February 2006 in a single institution, were prospectively entered into a computerized database. One thousand eighteen colorectal resections and 811 anastomoses were performed over this 40-month period. The most frequent procedures were sigmoid (276) and right colectomies (217). The overall anastomotic leak rate was 3.8%. The mortality rate associated with anastomotic leak was 12.9%. In univariate analysis, the following parameters were associated with an increased risk for anastomotic dehiscence: (1) ASA score ≥ 3 ( p = 0.004), (2) prolonged (>3 h) operative time ( p = 0.02), (3) rectal location of the disease ( p < 0.001), (4) and a body mass index > 25 ( p = 0.04). In multivariate analysis, ASA score ≥ 3 (OR = 2.5; 95% CI 1.5–4.3, p < 0.001), operative time > 3 h [OR = 3.0; 95% CI 1.1–8.0, p = 0.02), and rectal location of the disease (OR = 3.75; 95% CI 1.5–9.0 (vs left colon), p = 0.003; OR = 7.69; 95% CI 2.2–27.3 (vs right colon), p = 0.001] were factors significantly associated with a higher risk of anastomotic dehiscence. Three risk factors for anastomotic leak have been identified, one is patient-related (ASA score), one is disease-related (rectal location), the third being surgery-related (prolonged operative time). These factors should be considered in perioperative decision-making regarding defunctioning stoma formation. [ABSTRACT FROM AUTHOR]

Aim: Postoperative ileus is an important factor of complications following gastrointestinal procedures. Its pathophysiology and the parameters, which may impact on its duration, remain unclear. The aim of this study was to measure the role of various clinical determinants on restoration of intestinal function after elective colorectal surgery. Methods: From July 2002 to September 2003, all patients who underwent laparotomy for colectomy (laparoscopic resections excluded) with either an ileotransverse, colocolic, or high colorectal anastomosis were entered in this prospective study. The intervals in hours between the end of the surgical procedure and passing of flatus (PG) and passing of stool (PS) were recorded by an independent investigator. PG and PS were eventually correlated with the following parameters: type of colectomy, early removal of nasogastric tube (NGT), mechanical bowel preparation (MBP), type of underlying disease, systemic administration of opiates, and surgical training (colorectal fellowship or other). Results: One hundred twenty-four patients were entered in this study. Four patients (3.2%) developed septic complications (3 anastomotic leaks and 1 intraabdominal abscess) and were excluded from the analysis. Median age in this population was 68 (range 30–95) years. Mean duration of postoperative ileus was 70±28 h (PG) and 99±34 h (PS). The type of colectomy, underlying disease, MBP, and early NGT removal failed, in univariate analysis, to correlate with the duration of postoperative ileus. By contrast, time intervals PG and PS were statistically shorter in the group of patients treated by a colorectal surgeon [56±23 vs 74±28 h (PG); 82±26 vs 103±35 h (PS), p=0.004], as well as in patients who received systemic opiates for less than 2 days [64±27 vs 75±28 h (PG), p=0.04; 88±32 vs 108±33 h (PS), p=001]. Conclusion: Restoration of normal intestinal function after elective open colectomy takes 3 (PG) to 4 (PS) days. In our series, specialized training in colorectal surgery has a positive impact on the duration of postoperative ileus. Surgical specialization should be considered an important parameter in future clinical trials aiming to minimize postoperative ileus. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article related to laparoscoendoscopic cholecystectomy and occult gallbladder cancer, published in a previous issue.

A letter to the editor is presented in respone to an article on single-port access to laparoendoscopic single-site cholecystectomy that was published in a previous issue.

A letter to the editor is presented in response to the article regarding transvaginal endoscopic appendectomy in human, and the letters regarding the natural orifice transluminal endoscopic surgery (NOTES) procedures in the 2008 issue.