BACKGROUND: Enhanced recovery program is a multimodal, multidisciplinary-team, evidence-based care approach to reduce perioperative surgical stress, decrease morbidity and hospital stay, and improve recovery after surgery. This program may be most beneficial for elderly (≥70 y), but sparse series have investigated this question. OBJECTIVE: Feasibility and efficiency of a dedicated enhanced recovery program in the elderly as compared with standard care were studied. DESIGN: This was a nonblinded, randomized controlled study. SETTINGS: This study was conducted in a single high-volume university hospital. PATIENTS: A total of 150 eligible elderly patients undergoing elective colorectal surgery were included. INTERVENTIONS: Enhanced recovery after colorectal elective surgery in elderly patients was studied. MAIN OUTCOME MEASURES: The primary outcome was 30-day postoperative morbidity. Additional outcomes included hospital stay, readmission, postoperative pain, opioid consumption, independence preservation, and protocol compliance. RESULTS: An enhanced recovery program reduces postoperative morbidity according to Clavien-Dindo classification by 47% as compared with standard care (35% vs 65%; p = 0.0003), total number of complications (54 vs 118; p = 0.0003), and infectious complications (13 vs 29; p = 0.001). No anastomotic leak was recorded in the enhanced recovery group versus 5 for the standard group (p = 0.01). The enhanced recovery program resulted in shorter hospital stay (7 vs 12 d; p = 0.003) and better independence preservation (home discharge, 87% vs 67%; p = 0.005). A high protocol compliance of 77.2% could be achieved in this population. According to multivariate analysis, enhanced recovery program was strongly associated with reduced morbidity (OR = 0.23 (95% CI, 0.09–0.57); p = 0.001), less severe complications (OR = 0.36 (95% CI, 0.15–0.84); p = 0.02), and shorter hospital stay (OR = 2.07 (95% CI, 1.33–3.22); p = 0.001). LIMITATIONS: Limitations were a single-center recruitment and the impossibility of subject or healthcare professional blinding attributed to the nature of this multimodal program. CONCLUSIONS: Enhanced recovery program is safe and improves postoperative recovery in elderly patients with decreased morbidity, shorter hospital stay, and better maintenance of independence. It should therefore be considered as a standard of care for elective colorectal surgery in elderly patients. See Video Abstract at http://links.lww.com/DCR/A981. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01646190. ENSAYO CONTROLADO ALEATORIZADO DE UN PROGRAMA DE RECUPERACIÓN INTENSIFICADA DEDICADO A PACIENTES DE EDAD AVANZADA DESPUÉS DE CIRUGÍA COLORECTAL ANTECEDENTES: El Programa de Recuperación Intensificada es un enfoque de atención multimodal, multidisciplinaria y basada en evidencia para reducir el estrés quirúrgico perioperatorio, disminuir la morbilidad y la estancia hospitalaria, y mejorar la recuperación después de la cirugía. Este programa puede ser más beneficioso para las personas mayores (≥70 años), pero pocas series han investigado esta pregunta. OBJETIVO: Viabilidad y eficiencia del Programa de Recuperación Intensificada dedicado en personas de edad avanzada en comparación con la atención estándar. DISEÑO: Este fue un estudio controlado, aleatorizado, sin método ciego. ESCENARIO: Este estudio se realizó en un único hospital universitario de alto volumen. PACIENTES: Un total de 150 pacientes de edad avanzada elegibles sometidos a cirugía colorrectal electiva fueron incluidos. INTERVENCIONES: Recuperación Intensificada después de cirugía electiva colorrectal en pacientes de edad avanzada. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue la morbilidad postoperatoria a 30 días. Los resultados adicionales incluyeron estancia hospitalaria, reingreso, dolor postoperatorio, consumo de opioides, preservación de la independencia y cumplimiento del protocolo. RESULTADOS: El Programa de Recuperación Intensificada reduce la morbilidad postoperatoria según la clasificación de Clavien-Dindo en un 47% en comparación con la atención estándar (35% vs 65%; p = 0.0003), número total de complicaciones (54 vs 118; p = 0.0003) y complicaciones infecciosas (13 vs 29; p = 0.001). No se registró ninguna fuga anastomótica en el grupo de Recuperación Intensificada frente a 5 para el grupo estándar (p = 0.01). El Programa de Recuperación Intensificada dio como resultado una estancia hospitalaria más corta (7 contra 12 días; p = 0.003) y una mejor conservación de la independencia (alta hospitalaria: 87% vs 67%; p = 0.005). Se pudo lograr un alto cumplimiento del protocolo del 77.2% en esta población. De acuerdo con el análisis multivariable, el Programa de Recuperación Intensificada se asoció fuertemente con la reducción de morbilidad (OR = 0.23; IC 95%: 0.09–0.57; p = 0.001), menos complicaciones graves (OR = 0.36; IC 95%: 0.15–0.84; p = 0.02) y estancia hospitalaria más corta (OR = 2.07; IC 95%: 1.33–3.22; p = 0.001). LIMITACIONES: Las limitaciones fueron un centro único de reclutamiento y la imposibilidad de que los pacientes o el profesional de la salud tuvieran cegamiento debido a la naturaleza de este programa multimodal. CONCLUSIONES: El Programa de recuperación Intensificada es seguro y mejora la recuperación postoperatoria en pacientes de edad avanzada, con menor morbilidad, menor estancia hospitalaria y mejor mantenimiento de la independencia. Por lo tanto, debe considerarse como un estándar de atención para la cirugía colorrectal electiva en pacientes de edad avanzada. Vea el Resumen en video en http://links.lww.com/DCR/A981.

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 maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine 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.

ChemInformVolume 47, Issue 24 Natural Products ChemInform Abstract: Total Synthesis and Biological Assessment of Mandelalide A (I). Tobias Michael Bruetsch, Tobias Michael Bruetsch Dep. Chem. Appl. Biosci., Inst. Pharm. Sci., ETH, CH-8093 Zuerich, Switz.Search for more papers by this authorPascal Bucher, Pascal Bucher Dep. Chem. Appl. Biosci., Inst. Pharm. Sci., ETH, CH-8093 Zuerich, Switz.Search for more papers by this authorKarl-Heinz Altmann, Karl-Heinz Altmann Dep. Chem. Appl. Biosci., Inst. Pharm. Sci., ETH, CH-8093 Zuerich, Switz.Search for more papers by this author Tobias Michael Bruetsch, Tobias Michael Bruetsch Dep. Chem. Appl. Biosci., Inst. Pharm. Sci., ETH, CH-8093 Zuerich, Switz.Search for more papers by this authorPascal Bucher, Pascal Bucher Dep. Chem. Appl. Biosci., Inst. Pharm. Sci., ETH, CH-8093 Zuerich, Switz.Search for more papers by this authorKarl-Heinz Altmann, Karl-Heinz Altmann Dep. Chem. Appl. Biosci., Inst. Pharm. Sci., ETH, CH-8093 Zuerich, Switz.Search for more papers by this author First published: 27 May 2016 https://doi.org/10.1002/chin.201624213Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume47, Issue24May, 2016 RelatedInformation

The picture shows the marine macrolide mandelalide A together with the starting materials and advanced intermediates that have enabled a highly convergent total synthesis of the macrolactone core of this complex natural product. Like other bioactive macrocycles, mandelalide A is of polyketide origin and it has been described to exhibit antiproliferative activity against some human cancer cell lines, but not others. Here, mandelalide A was found to reduce the proliferation of two lung cancer cell lines with nM potency, but it did not kill all cells even at much higher concentrations. More information can be found in the Full Paper by K.-H. Altmann et al. on page 1292 ff.

Superior lumbar triangle hernia, also known as Grynfeltt-Lesshaft hernia, denotes a subtype of abdominal wall hernia, and more specifically of lumbar hernia, occurring between the 12th rib, the internal oblique muscle, and the quadratus lumborum muscle. We report the case of a 92-year-old female patient in which this form of hernia occurred, complicated by incarceration and acute bowel obstruction. The discussion contains a short résumé of the different kinds of abdominal wall hernias.

A new convergent total synthesis of the marine macrolide mandelalide A (1) has been developed that is based on macrocyclic ring closure by a Shiina-type macrolactonization and the construction of the requisite precursor seco acid by a highly efficient Sonogashira cross-coupling reaction between two fragments of comparable complexity. Key steps in the elaboration of the acid building block were the enantioselective, catalytic addition of a protected acetylene to crotonaldehyde and the construction of the tetrahydropyran unit that is embedded in the macrocycle by means of an acid-catalyzed Prins reaction. The synthesis of the alcohol fragment features the formation of the trisubstituted tetrahydrofuran ring through an acetal cleavage/epoxide opening cascade reaction and a rarely used radical alkynylation of a primary alkyl iodide. Intriguingly, the dihydroxylation of a terminal double bond as part of the synthesis of this building block gave the same major product for both the α- and β-AD-mix reagents, albeit with moderate or low selectivity. Synthetic mandelalide A (1) was a potent proliferation inhibitor of A549, HT460, and H1299 human lung cancer cells in vitro, but not of SK-N-SH neuroblastoma cells. However, in no case did we observe complete cell kill even at the highest compound concentration tested (5 μm).

Duodenal diverticula (DD) are frequently encountered and are usually asymptomatic, with an incidence at autopsy of 22%. Perforation of DD is a rare complication (around 160 cases reported) with potentially dramatic consequences. However, little evidence regarding its treatment is available in the literature. The aim of this study was to review our experience of perforated DD, with a focus on surgical management. Between January 2001 and June 2011, all perforated DD were retrospectively reviewed at a single centre. Seven cases (5 women and 2 men; median age: 72.4 years old, rang: 48-91 years) were found. The median American Society of Anesthesiologists' score in this population was 3 (range: 3-4). The perforation was located in the second portion of duodenum (D2) in six patients and in the third portion (D3) in one patient. Six of these patients were treated surgically: five patients underwent DD resection with direct closure and one was treated by surgical drainage and laparostomy. One patient was treated conservatively. One patient died and one patient presented a leak that was successfully treated conservatively. The median hospital stay was 21.1 d (range: 15-30 d). Perforated DD is an uncommon presentation of a common pathology. Diverticular excision with direct closure seems to offer the best chance of survival and was associated with a low morbidity, even in fragile patients.

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(2). 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.

Single access endoscopic surgery, also called laparoendoscopic single site surgery, single port access or single incision laparoscopic surgery has rapidly emerged in clinical practice for some specific indications. Among them single access cholecystectomy is rapidly diffusing in an attempt to improve cosmetic results, reduce parietal trauma, fasten recovery and answer patient's demand of this frequent surgery. While this approach is diffusing some limitations still persist in its feasibility, which have to be overcome by new development in instrumentations and refinement in techniques. And, on the other hand safety principle of minimally invasive cholecystectomy should be strictly respected to ensure our patients safe surgeries. Recent experiences and reports have shown that all these points can be respected, at least by experienced teams, while offering patients the first steps towards routine clinical scarless surgery. In this paper we will review the current status of cholecystectomy through single access endoscopic surgery regarding techniques, indications and results.

BACKGROUND AND STUDY AIMS:Very recently, robotic single site cholecystectomy (RSSC) has been reported feasible and safe for selected cases. While an intra-operative cholangiography can be performed, data is scarce with respect to its use. Indocyanin green (ICG) has been shown to be a viable option to visualize biliary anatomy. Since the introduction of a new near infrared camera integrated to the da Vinci Si System (Intuitive Surgical, Sunnyvale, CA), the surgeon is able to assess the biliary anatomy by a non-invasive and non-ionizing method. This paper presents the first report of ICG imaging during a RSSC.PATIENTS AND METHODS:Twelve consecutive patients presenting symptomatic cholelithiasis were prospectively enrolled. They underwent RSSC approximately 45 minutes after intravenous administration of ICG (2.5 mg). The biliary anatomy was analyzed using a near infrared camera integrated to the robot before and after the robotic dissection.RESULTS:Eight women and four men underwent the procedure. There was a port addition in one case and no peri-operative complications. Mean operative time was 85 minutes (range: 57-125). The cystic, common bile and common hepatic ducts were recognized by fluorescence imaging before the dissection in 91.7%, 50%, and 33.3% of patients, respectively. At least one structure was visualized in 100% of patients. After the completion of Calot's triangle dissection, the cystic, common bile, and common hepatic ducts were recognized in 100%, 83.3%, and 66.7% of cases respectively.CONCLUSIONS:RSSC using ICG for biliary tree fluorescence imaging can be performed safely. Fluorescent cholangiography enabled real-time identification of the extra-hepatic biliary anatomy using a near infrared camera integrated to the robot. Its routine clinical use merits further investigations.

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.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.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.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.

QUESTIONS UNDER STUDY/PRINCIPLES: In most centers, Upper Gastrointestinal series (UGI) following Roux-en-Y Gastric Bypass (RYGB) is performed to rule out GJ anastomotic leak. According to the introduction of robotic technology associated with a hypothetical decrease of anastomotic complications, we aim to assess the validity and cost effectiveness of early routine UGI following robot-assisted RYGB.METHODS: Between July 2006 and December 2010, 167 robot-assisted RYGB were performed at a single institution. All data were collected prospectively in a computerised database and reviewed retrospectively. Patients underwent a gastrografin UGI at postoperative day 2 to exclude anastomotic leak or stenosis.RESULTS: None of the 167 patients who underwent an early UGI experienced leak radiologically and clinically. The only radiological abnormalities were two GJ edema (1.2%) and one jejunojenunostomy stenosis (0.6%), all treated conservatively with success. The total cost for the 167 UGI was CHF 93,520 (= USD 96,886).CONCLUSIONS: In most centres, the risk of anastomotic leak has been the rationale for obtaining an UGI following RYGB. However, provided low leak rates as for our experience with robotic RYGB, the authors show this exam to be expensive and of limited value. A decisional algorithm for on demand UGI has been developed according to patient's characteristics and is now under validation.

BackgroundSingle-port laparoscopy attempts to further reduce thesurgical impact of minimally invasive surgery whencompared to conventional laparoscopy [1–4]. Single-portlaparoscopy might in general result in enhanced cosmeticoutcomes and potentially reduced pain when compared tothe conventional multi-port technique [5–8]. While manualsingle-port laparoscopy comes with certain technical lim-itations [1], a newly approved single-site platform usedwith the da Vinci Si Surgical System (Intuitive Surgical,Sunnyvale, CA, USA) might facilitate this technique. Wepresent the video of our 2nd patient undergoing this newtechnique.MethodsA 44-year-old female patient with a BMI of 26.8 kg/m

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.

Journal of the American College of Surgeons 212(3):p 422-423, March 2011. | DOI: 10.1016/j.jamcollsurg.2010.12.009

Background New technologies can considerably improve preoperative planning, enhance the surgeon's skill and simplify the approach to complex procedures. Augmented reality techniques, robot assisted operations and computer assisted navigation tools will become increasingly important in surgery and in residents’ education. Methods We obtained 3D reconstructions from simple spiral computed tomography (CT) slides using OsiriX, an open source processing software package dedicated to DICOM images. These images were then projected on the patient's body with a beamer fixed to the operating table to enhance spatial perception during surgical intervention (augmented reality). Results Changing a window's deepness level allowed the surgeon to navigate through the patient's anatomy, highlighting regions of interest and marked pathologies. We used image overlay navigation for laparoscopic operations such cholecystectomy, abdominal exploration, distal pancreas resection and robotic liver resection. Conclusions Augmented reality techniques will transform the behaviour of surgeons, making surgical interventions easier, faster and probably safer. These new techniques will also renew methods of surgical teaching, facilitating transmission of knowledge and skill to young surgeons.