Use and outcome of minimally invasive pancreatic surgery in the European E-MIPS registry.

BACKGROUND: The European registry for minimally invasive pancreatic surgery (E-MIPS) collects data on laparoscopic and robotic MIPS in low- and high-volume centers across Europe. METHODS: Analysis of the first year (2019) of the E-MIPS registry, including minimally invasive distal pancreatectomy (MIDP) and minimally invasive pancreatoduodenectomy (MIPD). Primary outcome was 90-day mortality. RESULTS: Overall, 959 patients from 54 centers in 15 countries were included, 558 patients underwent MIDP and 401 patients MIPD. Median volume of MIDP was 10 (7-20) and 9 (2-20) for MIPD. Median use of MIDP was 56.0% (IQR 39.0-77.3%) and median use of MIPD 27.7% (IQR 9.7-45.3%). MIDP was mostly performed laparoscopic (401/558, 71.9%) and MIPD mostly robotic (234/401, 58.3%). MIPD was performed in 50/54 (89.3%) centers, of which 15/50 (30.0%) performed ≥20 MIPD annually. This was 30/54 (55.6%) centers and 13/30 (43%) centers for MIPD respectively. Conversion rate was 10.9% for MIDP and 8.4% for MIPD. Overall 90 day mortality was 1.1% (n = 6) for MIDP and 3.7% (n = 15) for MIPD. CONCLUSION: Within the E-MIPS registry, MIDP is performed in about half of all patients, mostly using laparoscopy. MIPD is performed in about a quarter of patients, slightly more often using the robotic approach. A minority of centers met the Miami guideline volume criteria for MIPD.

Two Decades of Progress in the Asymmetric Intramolecular aza-Michael Reaction.

The asymmetric intramolecular aza-Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen-substituted stereocenters. Due to the ubiquitous presence of these skeletons in natural products, the IMAMR has found widespread applications in the total synthesis of alkaloids and biologically relevant compounds. The development of asymmetric versions of the IMAMR are quite recent, most of them reported in this century. The fundamental advances in this field involve the use of organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone-derived primary amines and quaternary ammonium salts, and BINOL-derived phosphoric acids account for the success of those methodologies. Moreover, the use of N-sulfinyl imines with a dual role, as nitrogen nucleophiles and as chiral auxiliaries, appeared as a versatile mode of performing the asymmetric IMAMR.

Predictors for stone recurrence after a successful common bile duct surgical exploration for choledocholithiasis.

BACKGROUND: Recurrence after common bile duct stone (CBDS) clearance is the major long-term drawback of their management. Its prevalence is significant, and it occurs after all primary therapeutic alternatives. The aim of this study was to determine the predictive factors associated with stone recurrence after surgical common bile duct exploration (CBDE). METHODS: A retrospective cohort study based on patients undergoing CBDE between 2000 and 2018 was conducted. Uni- and multivariate hierarchical regression analyses were performed to assess the independent predictive factors associated with recurrent CBDS in patients with initially successful surgery. RESULTS: A total of 365 patients underwent successful surgical procedures. After a median follow-up of 43.2 (IQR 84) months, 31 (8.4%) patients were diagnosed with CBD stone recurrence. The median time to recurrence was 30.3 (IQR 38) months. The only variable associated with CBDS recurrence was preoperative endoscopic sphincterotomy (HR 2.436, 95% CI: 1.031-5.751, P = 0.042)). CONCLUSION: Patients who undergo preoperative endoscopic sphincterotomy and then cholecystectomy with successful common bile duct clearance may be at increased risk for recurrent stone disease compared to those who go straight to surgery.

Conversion to open surgery during laparoscopic common bile duct exploration: predictive factors and impact on the perioperative outcomes.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is an effective treatment for choledocholithiasis. The aim of this study was to determine the predictive factors associated with conversion during LCBDE and to assess the implications of conversion on the patients' postoperative course. METHODS: A retrospective cohort study based on patients undergoing LCBDE between 2000 and 2018 was conducted. Uni- and multivariate regression analyses were performed. RESULTS: A total of 357 patients underwent LCBDE, and the conversion rate was 14.2%. The main reasons for conversion were lithiasis extraction (21; 41%) and difficult dissection (13; 26%). Independent predictors for conversion were increasing levels of serum bilirubin prior to surgery (OR=4.745, 95% CI: 1.390-16.198; p=0.013), and emergency setting (OR=4.144, 95% CI: 1.449-11.846; p=0.008). Age was independently associated with lower odds of conversion (OR=0.979, 95% CI: 0.960-0.999; p=0.036). Conversion had a negative impact on the patients' postoperative course, including severe complication (21.6% vs. 5.2% p<0.001) and surgical reintervention (11.8% vs. 2.6% p=0.002) rates. CONCLUSION: Conversion to open surgery during LCBDE was associated with increased postoperative morbidity. Emergency surgery and increasing levels of serum bilirubin previous to surgery independently increase the probability of conversion; however age was independently associated with lower odds of conversion.

Double asymmetric intramolecular aza-Michael reaction: a convenient strategy for the synthesis of quinolizidine alkaloids.

A new methodology to access the quinolizidine skeleton in an asymmetric fashion was devised. It involves two consecutive intramolecular aza-Michael reactions of sulfinyl amines bearing a bis-enone moiety, in turn generated by a monodirectional cross metathesis reaction. The sequence, which takes place with excellent yields and diastereocontrol, was applied to the total synthesis of alkaloids lasubine I and myrtine.

Laparoscopic staged colon-first resection for metastatic colorectal cancer: Perioperative and midterm outcomes from a single-center experience.

INTRODUCTION: The present study aimed to evaluate the short- and mid-term outcomes of laparoscopic colon-first staged resection for colorectal cancer (CRC) and colorectal cancer liver metastases (CRCLM). METHODS: This study included patients with metastatic CRC who underwent laparoscopic surgical staged resection for the primary tumor and CRCLM between June 2013 and December 2018. Data collection included the baseline patient's and tumor features, the perioperative and histopathologic outcomes from both surgical procedures, and the oncologic follow-up. RESULTS: Twenty-five patients were eligible for the study. Three major and 22 minor laparoscopic liver resections were performed following laparoscopic CRC surgery. Five patients required conversion to laparotomy during CRCLM resection, but no conversion was needed for the colorectal procedures. The rate of severe intraoperative complications (CLASSIC grade III-IV) was 8% and 16% during CRC and CRCLM resection, respectively. Three patients (12%) developed major postoperative complications (Clavien-Dindo grade > III) after both interventions, including one death due to intraoperative bleeding. During a median follow-up of 30 months, 15 patients were diagnosed with disease recurrence. The 3-year disease-free survival and overall survival were 33.3% and 73.9%, respectively. CONCLUSIONS: Laparoscopic staged resection for CRC and CRCLM is safe, feasible, and offers acceptable midterm oncological outcomes in patients with metastatic colorectal cancer.

Optimum Expanded Fraction for an Industrial, Collins-Based Nitrogen Liquefaction Cycle.

Industrial nitrogen liquefaction cycles are based on the Collins topology but integrate variations. Several pressure levels with liquefaction to medium pressure and compressor-expander sets are common. The cycle must be designed aiming to minimise specific power consumption rather than to maximise liquid yield. For these reasons, conclusions of general studies cannot be extrapolated directly. This article calculates the optimal share of total compressed flow to be expanded in an industrial Collins-based cycle for nitrogen liquefaction. Simulations in Unisim Design R451 using Peng Robinson EOS for nitrogen resulted in 88% expanded flow, which is greater than the 75-80% for conventional Collins cycles with helium or other substances. Optimum specific compression work resulted 430.7 kWh/ton of liquid nitrogen. For some operating conditions, the relation between liquid yield and specific power consumption was counterintuitive: larger yield entailed larger consumption. Exergy analysis showed 40.3% exergy efficiency of the optimised process. The exergy destruction distribution and exergy flow across the cycle is provided. Approximately 40% of the 59.7% exergy destruction takes place in the cooling after compression. This exergy could be used for secondary applications such as industrial heating, energy storage or for lower temperature applications as heat conditioning.

Tandem Organocatalytic Cycloaromatization/Intramolecular Friedel-Crafts Alkylation Sequence for the Synthesis of Indolizinones and Pyrrolo-azepinone Derivatives.

The organocatalytic synthesis of indolizinones and pyrrolo-azepinones has been accomplished in a tandem fashion through a sequence that comprises initial cycloaromatization followed by intramolecular Friedel-Crafts alkylation. The process takes place under Brønsted acid catalysis, giving rise to final products in moderate to good yields. Attempts to carry out the tandem protocol in an enantioselective fashion were performed with chiral (R)-BINOL-derived N-triflyl phosphoramides. After initial optimization, the tandem process took place with moderate levels of enantioselectivity.

Synthesis of substituted piperidines by enantioselective desymmetrizing intramolecular aza-Michael reactions.

An organocatalytic enantioselective intramolecular aza-Michael reaction has been described for the first time in a desymmetrization process employing substrates different from cyclohexadienones. By using 9-amino-9-deoxy-epi-hydroquinine as the catalyst and trifluoroacetic acid as a co-catalyst, a series of enantiomerically enriched 2,5-and 2,6-disubstituted piperidines have been obtained in good yields and with moderate diastereoselectivity. Depending on the catalyst/co-catalyst loading ratio, either the major or the minor diastereoisomer of the final piperidine products was achieved with high levels of enantioselectivity. Finally, some mechanistic insights have been considered by means of theoretical calculations which were in agreement with the experimental results obtained in the desymmetrization reaction.

Fluorine and Gold: A Fruitful Partnership.

Gold-catalyzed reactions have witnessed an exponential growth in the past decade. When the unique modes of activation exhibited by gold species meet species with either fluorinated building blocks or fluorinating reagents, new opportunities arise for the development of new methodologies in fluoroorganic chemistry. Indeed, gold and fluorine truly formed a very fruitful partnership, and different types of reactivity emerged from their combination. This review gives an overview of such endeavors. The special properties imparted by fluorine to organic molecules have been exploited in gold-catalyzed processes, allowing for the generation of unprecedented fluorinated chemical entities. Thus, the interaction of gold salts with fluorinated building blocks has been revised. In a second section, recent developments in gold-catalyzed nucleophilic fluorinations have been covered. The development of new gold catalysts that stabilize the Au-F bond as well as recent mechanistic studies in the field raised the interest of these types of methodologies for the generation of new C-F bonds. The use of electrophilic fluorine sources enabled new modes of gold catalysis. The incorporation of Selectfluor as an external oxidant constituted a new paradigm in gold chemistry, incorporating the elusive Au(I)/Au(III) redox couple in gold-catalyzed transformations. This strategy provided access to both new fluorinated chemical entities and nonfluorinated derivatives by means of coupling reactions. Those topics have been reviewed in the last two sections.

Intramolecular Nitrone Cycloaddition of α-(Trifluoromethyl)styrenes. Role of the CF3 Group in the Regioselectivity.

The intramolecular 1,3-dipolar cycloaddition of ortho-substituted 1,1,1-trifluoromethylstyrene-derived nitrones is described. Tricyclic fused isoxazolidines were obtained as major or exclusive products, in contrast to the case for nonfluorinated substrates, which rendered the bridged derivatives. This change in the regioselectivity was attributed to the electronic and, particularly, steric requirements of the trifluoromethyl group in comparison to the methyl group. It is worth mentioning that trifluoromethylstyrenes have been employed for the first time as dipolarophiles in a 1,3-dipolar intramolecular cycloaddition reaction, leading to the corresponding isoxazolidines bearing a quaternary trifluoromethyl moiety. Finally, the synthetic utility of the developed methodology has been illustrated with the synthesis of a family of bicyclic fluorinated 1,3-amino alcohols.

Gold-Catalyzed Povarov-Type Reaction of Fluorinated Imino Esters and Furans.

A gold-catalyzed Povarov-type reaction of fluorinated imino esters and furans is described. The process, which takes place in dichoromethane at room temperature, gives rise to novel fluorinated tetrahydrofuran-fused tetrahydroquinolines in good yields and moderate levels of diastereoselectivity in a very simple manner. The reported examples expand the versatility of the Povarov reaction to unprecedented fluorinated substrates, generating scaffolds that contain quaternary α-amino acid units.

Eleven years of primary closure of common bile duct after choledochotomy for choledocholithiasis.

BACKGROUND: The choice of surgical technique to extract stones from the common bile duct (CBD) depends on local experience, anatomical characteristics and also on the size, location and number of stones. Most authors consider choledochotomy an alternative to failed transcystic exploration, although some use it exclusively. Although the CBD is traditionally closed with T-tube drainage after choledochotomy, its use is associated with 11.3-27.5 % morbidity. This study examined the efficacy of laparoscopic CBD exploration (LCBDE) with primary closure for the treatment of CBD stones using intraoperative cholangiography (IOC). METHODS: Retrospective study of 160 patients who underwent LCBDE with primary closure after choledochotomy between January 2001 and December 2012. RESULTS: The diagnosis of choledocholithiasis was definitively made in all cases by IOC. The overall complication rate was 15 % and the biliary complication rate was 7.5 %. Bile leakage was reported in 11 patients (6.8 %). In over half the cases (63.6 %), no further action was required and the leak closed spontaneously. Six patients were reoperated (3.75 %), two for bile peritonitis and four for haemoperitoneum. The success rate for stone clearance was 96.2 %. The mortality rate and CBD stricture rate were 0 %. CONCLUSION: Primary closure after choledochotomy to clear stones from the CBD is a safe technique that confers excellent results and allows one-stage treatment.

Laparoscopic surgery and polycystic liver disease: Clinicopathological features and new trends in management.

BACKGROUND: Polycystic liver disease (PLD) has a low frequency overall in the worldwide population. As the patient's symptoms are produced by the expansion of hepatic volume, the different therapeutic alternatives are focused on reducing it. Surgery is still considered the most effective treatment for symptomatic PLD. The aim of this study was to evaluate the long-term outcomes of laparoscopic surgery for PLD. MATERIALS AND METHODS: This study included 14 patients who were diagnosed with symptomatic PLD and underwent surgery by a laparoscopic approach between 2004 and 2012. It involved collecting data on the characteristics of those patients and their liver disease, surgical procedures, intra- and postoperative complications, and the long-term follow-up. RESULTS: Twelve laparoscopic multiple-cyst fenestrations and two segmentary liver resections associated with remaining-cyst fenestration were performed. One procedure required conversion to laparotomy and the other was complicated by anhepatic severe bleeding. The rest of the procedures were uneventful. One patient developed persistent self-limited ascites in the immediate postoperative period. Symptoms disappeared after surgical intervention in all patients. During a median follow-up of 62 months (range 14-113 months), there were two clinical recurrences and one asymptomatic radiological recurrence. One patient required further surgery. CONCLUSION: Laparoscopic cystic fenestration and laparoscopic liver resection are safe and long-term, effective procedures for the treatment of symptomatic PLD. Severity and morphological characteristics of the hepatic disease will determine the surgical indication and the optimal approach for each patient.

Enantioselective Palladium-Catalyzed Oxidative ß,ß-Fluoroarylation of α,ß-Unsaturated Carbonyl Derivatives.

The site-selective palladium-catalyzed three-component coupling of deactivated alkenes, arylboronic acids, and N-fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step-economical approach to the stereoselective ß-fluorination of α,ß-unsaturated systems.

Gold-catalyzed tandem hydroamination/formal aza-Diels-Alder reaction of homopropargyl amino esters: a combined computational and experimental mechanistic study.

A tandem gold-catalyzed hydroamination/formal aza-Diels-Alder reaction is described. This process, which employs quaternary homopropargyl amino ester substrates, leads to the formation of an intrincate tetracyclic framework and involves the generation of four bonds and five stereocenters in a highly diastereoselective manner. Theoretical calculations have allowed us to propose a suitable mechanistic rationalization for the tandem protocol. Additionally, by studying the influence of the ligands on the rate of the gold-catalyzed reactions, it was possible to establish optimum conditions in which to perform the process with a variety of substituents on the amino ester substrates. Notably, the asymmetric version of the tandem reaction was also evaluated.

A general overview of the organocatalytic intramolecular aza-Michael reaction.

The organocatalytic intramolecular aza-Michael reaction gives access to enantiomerically enriched nitrogen-containing heterocycles in a very simple manner. Enals, enones, conjugated esters and nitro olefins have been employed as Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides, carbamates and amides have been shown to be appropriate Michael donors in this type of reaction. Additionally, the process has been performed under both covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones, thioureas and chiral binol phosphoric acids being the most frequently used catalysts. The level of efficiency reached with this protocol is demonstrated by the implementation of numerous tandem processes, as well as the total synthesis of several natural products.

Tandem cross enyne metathesis (CEYM)-intramolecular Diels-Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds.

A new tandem cross enyne metathesis (CEYM)-intramolecular Diels-Alder reaction (IMDAR) has been carried out. It involves conjugated ketones, esters or amides bearing a remote olefin and aromatic alkynes as the starting materials. The overall process enables the preparation of a small family of linear bicyclic scaffolds in a very simple manner with moderate to good levels of diastereoselectivity. This methodology constitutes one of the few examples that employ olefins differently than ethylene in tandem CEYM-IMDAR protocols.

Microwave-assisted tandem organocatalytic peptide-coupling intramolecular aza-Michael reaction: α,ß-unsaturated N-acyl pyrazoles as Michael acceptors.

Conjugated N-acyl pyrazoles have been successfully employed in the organocatalytic enantioselective intramolecular aza-Michael reaction as ester surrogates. Bifunctional squaramides under microwave irradiation provided the best results in this transformation. Furthermore, this protocol has been combined with a peptide-coupling reaction in a tandem sequence. The final products were easily converted into the corresponding ethyl esters.

Tandem gold self-relay catalysis for the synthesis of 2,3-dihydropyridin-4(1 H)-ones: combination of σ and π Lewis acid properties of gold salts.

The dual ability of gold salts to act as π- and σ Lewis acids has been exploited in a tandem self-relay catalysis. Thus, triphenylphosphanegold(I) triflate mediated the intramolecular carbonyl addition of the amide functionality of homoprogargyl amides to a triple bond. The formation of a σ complex of the gold salt with the intermediate oxazine promoted a nucleophilic addition followed by a Petasis-Ferrier rearrangement. This tandem protocol, catalyzed by the same gold salt under the same reaction conditions, gave rise to the efficient synthesis of 2,3-dihydropyridin-4-(1 H)-ones, which contain a cyclic quaternary α-amino acid unit. The asymmetric version was performed by generating the starting materials from the corresponding sulfinylimines.