Enantioselective Desymmetrization of cis-3,5- O-Arylidenecyclohexanones Catalyzed by Cinchona-Derived Quaternary Ammonium Salts.

An enantioselective protocol for the desymmetrization of cis-3,5- O-arylidenecyclohexanones has been developed that proceeded under the catalysis of readily available and inexpensive Cinchona-derived quaternary ammonium salts. The synthetic relevance of the methodology was exemplified by the synthesis of a key intermediate that could be used in the preparation of the active pharmaceutical ingredient, paricalcitol (Zemplar).

Single-access laparoscopic "lavage" for purulent diverticulitis in a 96-year-old patient: how to reduce surgical trauma and standardize surgical technique.

INTRODUCTION: Recently, laparoscopic lavage emerged as an effective alternative for patients with perforated diverticulitis with purulent peritonitis. CASE REPORT: A 96-year-old woman, diagnosed with Hinchey 3 diverticulitis after a computed tomography scan, was operated on with a single-access "lavage" to reduce surgical trauma and to avoid stoma. METHODS: The procedure was performed under general anesthesia. Tracheal intubation, nasogastric tube, and urethral catheterization were mandatory. The patient was in a modified Lloyd-Davis position, with the table tilted in Trendelenburg position, left side up. Surgeons were on the right side. INSTRUMENTATION: The procedure was performed using a surgical technique similar to standard laparoscopy with traditional laparoscopic instruments. SURGICAL STEPS: The surgical procedure involved single-incision laparoscopic surgery (Covidien, Mansfield, MA) insertion, small bowel dissection, abscess opening, and peritoneal washing. RESULTS: The procedure was completed in 75 minutes with an estimated blood loss of 120 mL. The patient was kept in the intensive care unit for 1 day. She was on postoperative analgesia for 2 days and was discharged from the hospital on postoperative day 5. The patient was able to drink on day 1 and eat on day 3 after flatus.

Pharyngolaryngo-esophagectomy with laparoscopic gastric pull-up: a reappraisal for the pharyngoesophageal junction cancer.

BACKGROUND: Surgical treatment of advanced hypopharyngeal tumors is still a surgical challenge. We report a case of a hypopharyngeal tumor treated with a pharyngolaryngo-esophagectomy (PLE) and laparoscopic gastric tubulization and interposition. METHODS: A 56-year-old man presented with a relapsing hypopharynx carcinoma, after primary chemoradiation therapy. Preoperative workup showed a stage IV cancer with esophageal invasion and multiple cervical lymph node metastases. Surgical treatment consisted of a cervical phase, with larynx, pharynx, and esophagus dissection, radical lymph node dissection, homolateral hemithyroidectomy and definitive tracheostomy, and an abdominal phase with a 4-trocar laparoscopy. The gastrocolic ligament was opened, and short gastric and left gastric vessels were divided preserving an accessory left hepatic artery. Gastric tailoring was carried out with 45-mm linear staplers. The hiatus was opened and the esophagus dissected free with Ultracision (Ethicon Endo-Surgery, Cincinnati, OH) to the tracheal bifurcation. The upper esophagus was bluntly mobilized by finger and sponge stick dissection. The gastric tube was pulled up, and the anastomosis between the stomach and the tongue base was performed with a 2-layer interrupted hand-sewn technique. RESULTS: Total operative time was 390 min (abdominal time 180 min). Estimated blood loss was 400 cc. The number of dissected cervical lymph nodes was 32. Oral feeding was started after 10 days, and the patient was discharged after 14 days. Stage of disease was pT4N1M0 G3 R0. CONCLUSIONS: Laparoscopic surgery allows a minimally invasive gastric tailoring and tubulization and transhiatal esophageal dissection and represents a valuable alternative for intestinal reconstruction after PLE. CT scan showing a large hypopharynx carcinoma involving cervical lymph nodes and cervical esophagus.

Image-guided robotic radiosurgery (CyberKnife) for pancreatic insulinoma: is laparoscopy becoming old?

Insulinomas constitute about 25% of endocrine pancreatic tumors. Laparoscopic surgery is the treatment of choice. However, pancreas-related complications rate is very high, even in experienced hands, ranging up to 37%. Alternative procedures such as embolization with trisacryl have not been accepted by the surgical community. Image-guided robotic radiosurgery or stereotactic radiosurgery (CyberKnife) is a minimally invasive procedure delivering large doses of ionizing radiation to a well-defined target. CyberKnife radiosurgery is successfully used in brain cancer, lung cancer, prostate cancer, liver metastases, kidney cancer, and pancreatic cancer. The authors present the first case to their knowledge of a benign functioning insulinoma successfully treated by a CyberKnife technique with a 3-year follow-up.

Standard laparoscopic versus single-incision laparoscopic colectomy for cancer: early results of a randomized prospective study.

BACKGROUND: Standard laparoscopic colectomy (SLC) for cancer is a safe, feasible, and oncologically effective procedure with better short-term and similar long-term results of open colectomy. Conversely, owing to technical difficulties in colonic resection and full mesenteric dissection, single-incision laparoscopic colectomy (SILC) has been considered unsuitable for oncologic purposes. We compared the technical feasibility and early clinical outcomes of SLC and SILC for cancer. METHODS: In this prospective randomized clinical trial, 16 (50%) patients underwent SLC (10 left and 6 right) and 16 (50%) patients underwent SILC (8 left and 8 right). RESULTS: Demographics, preoperative data, and characteristics of the tumor were similar. The mean number of resected lymph nodes was 16 ± 5 in the SLC and 18 ± 6 in the SILC group (P = NS). Surgical time was 124 ± 8 minutes and 147 ± 5 minutes, respectively (P = NS). Surgical mortality was nil and the major morbidity rate was 6.3% in both groups. CONCLUSIONS: SILC for cancer is a technically feasible and safe oncologic procedure with short-term results similar to those obtained with a traditional laparoscopic approach.

Laparoscopic left nephrectomy with "en bloc" distal splenopancreatectomy.

BACKGROUND: Multiorgan resection for cancer is considered a demanding laparoscopic procedure. We report a laparoscopic radical nephrectomy and distal splenopancreatectomy for a locally advanced kidney tumor. METHODS: A 67-year-old woman presented with left flank pain and hematuria. CT scan showed a left kidney upper pole large mass with direct extension to spleen and pancreatic tail, but not metastases. With the patient on the right flank, three 10-mm trocars were placed forming an isosceles triangle in the left subcostal arch. Entering the lesser sac, splenic vessels were separately divided between clips. The pancreatic tail was dissected free and divided with Ultracision. The left renal vein was dissected free, and the aorta was exposed to perform the lymphadenectomy. Superior mesenteric artery and left renal vein and artery were isolated, and renal vessels were separately divided with a vascular stapler. The left kidney was mobilized. The specimen was inserted in a bag and retrieved transvaginally through a posterior colpotomy. RESULTS: Total operation time was 210 minutes. Estimated blood loss was 250 mL. The patient was discharged after 7 days. Final stage of disease was pT4N0M0 G2 R0 renal cell carcinoma. The patient came back 6 years later presenting a ductal adenocarcinoma of pancreatic head. At the second look laparoscopy, very few adhesions were found in right upper quadrant, and the posterior colpotomy scar was very small. The patient died 1 year after Whipple operation. CONCLUSIONS: Oncologic rules of an "en bloc" resection can be respected also with a laparoscopic approach.

Unexpected side reactions of imidazolium-based ionic liquids in the base-catalysed Baylis-Hillman reaction.

Low yields are obtained when the Baylis-Hillman reaction is conducted in the presence of an imidazolium-based ionic liquid due to direct addition of the deprotonated imidazolium salt to the aldehyde. Ionic liquids are evidently not inert.

Rate acceleration of the Baylis-Hillman reaction in polar solvents (water and formamide). Dominant role of hydrogen bonding, not hydrophobic effects, is implicated.

A substantial acceleration of the Baylis-Hillman reaction between cyclohexenone and benzaldehyde has been observed when the reaction is conducted in water. Several different amine catalysts were tested, and as with reactions conducted in the absence of solvent, 3-hydroxyquinuclidine was found to be the optimum catalyst in terms of rate. The reaction has been extended to other aldehyde electrophiles including pivaldehyde. Attempts to extend this work to acrylates was only partially successful as rapid hydrolysis of methyl and ethyl acrylates occurred under the base-catalyzed and water-promoted conditions. However, tert-butyl acrylates were sufficiently stable to couple with relatively reactive electrophiles. Further studies on the use of polar solvents revealed that formamide also provided significant acceleration and the use of 5 equiv of formamide (optimum amount) gave faster rates than reactions conducted in water. Using formamide, further acceleration was achieved in the presence of Yb(OTf)(3) (5 mol %). The scope of the new conditions was tested with a range of Michael acceptors and benzaldehyde and with a range of electrophiles and ethyl acrylate. The origin of the rate acceleration is discussed.

Metal- and Ligand-Accelerated Catalysis of the Baylis-Hillman Reaction.

The Baylis-Hillman reaction, the coupling of an unsaturated carbonyl compound/nitrile with aldehydes, is a valuable reaction but is limited in its practicality by poor reaction rates. We have endeavored to accelerate the reaction using Lewis acids and found that while conventional Lewis acids gave reduced rates group III, and lanthanide triflates (5 mol %) gave increased rates. The optimum metal salts were La(OTf)(3) and Sm(OTf)(3), which gave rate accelerations (k(rel)) of approximately 4.7 and 4.9, respectively, in reactions between tert-butyl acrylate and benzaldehyde when using stoichiometric amounts of DABCO. At low loadings of DABCO (up to 10 mol %), no reaction occurred due to association of DABCO with the metal. Use of additional ligands to displace the DABCO from the metal was studied, and the rate of reaction was found to increase further in most cases. Of the ligands tested, at 5 mol %, (+)-binol gave one of the largest rate accelerations (3.4-fold) and was studied in more detail. It was found that reactions occurred even at low DABCO concentration so that here the Lewis base and Lewis acid were able to promote the reaction without interference from each other. While the (+)-binol (and other chiral ligands) failed to provide any significant asymmetric induction, a substantial nonlinear effect was observed with binol. Thus, use of racemic binol gave no effect on the rate. In seeking to maximize the rate attainable, more soluble (liquid) ligands were studied. Diethyl tartrate and triethanolamine gave rate enhancements of 5.2x and 3.5x at 50 mol %, respectively, versus 1.5x and 2.3x at 5 mol %. The best protocol was to use 100 mol % DABCO, 50 mol % triethanolamine, and 5 mol % La(OTf)(3). This gave overall rate accelerations of between 23-fold and 40-fold depending on the acrylate and approximately 5-fold for acrylonitrile. A simple acid wash removed the reagents, leaving the product in the organic phase. While triethanolamine accelerated the reaction without the lanthanum triflate (18-22-fold at 80 mol %), the reaction in the presence of the metal salt was faster. The system was tested synthetically on various substrates and found to give good rate accelerations with both activated (benzaldehyde and p-nitrobenzaldehyde) and less activated aldehydes (anisaldehyde and cyclohexanecarboxaldehyde) with acrylates. The limited amount of dimerized acrylate in the latter reactions is noteworthy and should extend the range of substrates that can be made by the Baylis-Hillman reaction using our optimum conditions.