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(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.
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An aneurysm is a vascular malformation that can be classified according to its location (cerebral, aortic) or shape (saccular, fusiform, and mycotic). Recently, the study of blood flow interaction with aneurysms has gained attention from physicians and engineers. Shear stresses, oscillatory shear index (OSI), gradient oscillatory number (GON), and residence time have been used as variables to describe the hemodynamics as well as the origin and evolution of aneurysms. However, the causes and hemodynamic conditions that promote their growth are still under debate. The present work presents numerical simulations of three types of aneurysms: two aortic and one cerebral. Simulation results showed that the blood rheology is not relevant for aortic aneurysms. However, for the cerebral aneurysm case, blood rheology could play a relevant role in the hemodynamics. The evaluated turbulence models showed equivalent results in both cases. Lastly, a simulation considering the fluid-structure interaction (FSI) showed that this phenomenon is the dominant factor for aneurysm simulation.
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The enantioselective synthesis of fluorinated indolizidinone derivatives has been developed. The process involved an enantioselective intramolecular aza-Michael reaction of conjugated amides bearing a pendant α,ß-unsaturated ketone moiety, catalyzed by the (S)-TRIP-derived phosphoric acid, followed by dimethyltitanocene methylenation and ring closing metathesis (RCM). Final indolizidine-derived products comprise a fluorine-containing tetrasubstituted double bond generated by the RCM reaction, which is a challenging task. The whole synthetic sequence took place in acceptable overall yields with excellent enantioselectivities.
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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.
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Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias Pancreáticas/cirugía , Procedimientos Quirúrgicos Robotizados/efectos adversos , Páncreas/cirugía , Pancreatectomía/efectos adversos , Pancreaticoduodenectomía/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos , Laparoscopía/efectos adversos , Sistema de Registros , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
BACKGROUND/PURPOSE: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers. METHODS: A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien-Dindo grade at least III complications, readmission, or mortality within 90 postoperative days. RESULTS: A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55-72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50-82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 ( P =0.016), intrahepatic versus extrahepatic tumor ( P =0.027), single versus multiple tumors ( P =0.007), those who underwent hepatic versus pancreatic resection ( P =0.017), or achieved versus failed TO ( P =0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11-15.94; P =0.03) was an independent prognostic factor of poor overall survival. CONCLUSIONS: Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.
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Neoplasias de los Conductos Biliares , Carcinoma Papilar , Humanos , Femenino , Anciano , Masculino , Conductos Biliares Intrahepáticos/cirugía , Estudios Retrospectivos , Conductos Biliares/patología , Carcinoma Papilar/cirugíaRESUMEN
The interest in 3,4-dihydropyrimidine-2(1H)-(thio)ones is increasing every day, mainly due to their paramount biological relevance. The Biginelli reaction is the classical approach to reaching these scaffolds, although the product diversity suffers from some limitations. In order to overcome these restrictions, two main approaches have been devised. The first one involves the modification of the conventional components of the Biginelli reaction and the second one refers to the postmodification of the Biginelli products. Both strategies have been extensively revised in this manuscript. Regarding the first one, initially, the modification of one of the components was covered. Although examples of modifications of the three of them were described, by far the modification of the keto ester counterpart was the most popular approach, and a wide variety of different enolizable carbonylic compounds were used; moreover, changes in two or the three components were also described, broadening the substitution of the final dihydropyrimidines. Together with these modifications, the use of Biginelli adducts as a starting point for further modification was also a very useful strategy to decorate the final heterocyclic structure.
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An enantioselective synthesis of polycyclic fluorinated pyrrolidines has been achieved by Cu-catalyzed intramolecular 1,3-dipolar cycloaddition of azomethine ylides with fluorinated dipolarophiles. The method displays a wide scope and afforded the desired cycloadducts in high yields with up to 99% ee. These results demonstrate that fluoroalkyl substituents are excellent activating groups in this transformation.
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Tiosemicarbazonas , Compuestos Azo , Catálisis , Reacción de Cicloadición , EstereoisomerismoRESUMEN
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.
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Colecistectomía Laparoscópica , Coledocolitiasis , Cálculos Biliares , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomía Laparoscópica/métodos , Coledocolitiasis/cirugía , Conducto Colédoco/cirugía , Cálculos Biliares/cirugía , Humanos , Recurrencia , Estudios RetrospectivosRESUMEN
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.
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Alcaloides , Iminas , Aminas , EstereoisomerismoRESUMEN
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.
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Colecistectomía Laparoscópica , Coledocolitiasis , Laparoscopía , Colecistectomía Laparoscópica/efectos adversos , Coledocolitiasis/diagnóstico por imagen , Coledocolitiasis/cirugía , Conducto Colédoco/cirugía , Conversión a Cirugía Abierta , Humanos , Laparoscopía/efectos adversos , Estudios RetrospectivosRESUMEN
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.
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A novel strategy for the synthesis of policyclic trifluoromethyl arenes has been devised. It involves a DBU-promoted tandem cycloaromatization reaction of dicyanoalkenes and fluorinated conjugated sulfinyl imines. This unprecedented transformation is a metal-free and air-tolerant process that takes place from readily available starting materials under mild reaction conditions.
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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.
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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.
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Colectomía/métodos , Neoplasias Colorrectales/cirugía , Hepatectomía/métodos , Laparoscopía/métodos , Neoplasias Hepáticas/secundario , Anciano , Anciano de 80 o más Años , Colectomía/efectos adversos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Hepatectomía/efectos adversos , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
INTRODUCTION: Since the appearance of SARS-CoV-2 in December 2019 in the Chinese city of Wuhan, we have experienced a reduction in admissions in our Service and a decrease in urgent surgical activity. Therefore, this study aimed to assess the incidence of potentially surgical abdominal emergency in our center during the epidemic of COVID-19. METHODS: A retrospective study was designed. It included all patients admitted for urgent abdominal pathology with potential surgical treatment in our General and Digestive Surgery Department from February 24, 2020 to April 19, 2020. RESULTS: Eighty-nine patients with a mean age of 58.85±22.2 were included. The median time from symptom onset to the Emergency Department (ED) visit was 48 (P25-P75 = 24-96) hours. On arrival at the ED, 18 (20%) patients presented with systemic inflammatory response syndrome criteria. Fifty-one (57%) surgical procedures were performed. The rate of post-surgical complications at 30 days was 31% and the mortality rate was 2%. Concerning the same period from 2017 to 2019, the mean number of admissions from the ED to our Department decreased by 14% during the epidemic period. CONCLUSION: There has been a decrease in the number of patients admitted for urgent, potentially surgical, abdominal pathology during the period of the COVID-19 epidemic in our center.
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Abdomen/cirugía , COVID-19/epidemiología , Enfermedades del Sistema Digestivo/epidemiología , Enfermedades del Sistema Digestivo/cirugía , Servicio de Urgencia en Hospital , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pandemias , Admisión del Paciente/tendencias , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias , Estudios Retrospectivos , SARS-CoV-2 , España/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/epidemiologíaRESUMEN
Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.
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Acromegalia/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Validación como AsuntoRESUMEN
An organocatalytic desymmetrizing intramolecular aza-Michael reaction with vinyl sulfonamides as nucleophilic nitrogen source has been devised for the synthesis of a new family of 2,5,5-trisubstituted piperidines bearing a quaternary sterocenter. The process takes place with excellent levels of enantioselectivity and moderate to good diastereoselectivity. The vinyl sulfonamide moiety can be removed by means of an ozonolysis reaction.
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Mixed divalent Cu, Co, Ni and Zn complexes containing the new sulfonamide ligand N-(2-(pyridin-2-yl)ethyl)quinoline-8-sulfonamide (HQSEP) were prepared and characterized by physico-chemical techniques. The tetracoordinate [Cu(QSEP)X] [Xâ¯=â¯Br (1), Cl (2)] compounds present a seesaw geometry (τ4â¯=â¯0.56 (1) and 0.50 (2)). The Cu(II) in the [Cu(QSEP)(NO3)(MeOH)] (3) complex is five coordinate with a slightly distorted SP geometry (τâ¯=â¯0.11). The [M(QSEP)(benz)] [Mâ¯=â¯Cu(II) (4), Ni(II) (5), Co(II) (6) and Zn(II) (7); benzâ¯=â¯benzoate] compounds are configurationally isotypic. The coordination geometries of the M(II) ions can be best described as distorted SP (τâ¯=â¯0.29, 0.15, 0.34 and 0.18 for 4, 5, 6 and 7, respectively). The interaction of the compounds with CT-DNA was studied by different techniques. Notably, these studies indicated that the tetracoordinate complexes (1 and 2) present higher DNA affinity than pentacoordinate compounds (3-7). In line with the Irving-Williams order of stability, 5 presented higher propensity for DNA binding than 6. Interestingly, the cleavage activity of 1-4 in the presence of ascorbate/H2O2 follows the same trend as that found for DNA binding affinity, being the tetracoordinate 1 and 2 more effective as nucleases than the five coordinate 3 and 4. Also, the DNA cleavage reaction mechanism was investigated. DNA cleavage experiments upon irradiation indicated the important role of the aromatic nature of the coligand in the photocleavage activity of 1-4. Finally, the interaction of the compounds with bovine serum albumin (BSA) was studied and the binding constants were calculated.
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División del ADN , ADN/química , Desoxirribonucleasas/química , Metales/química , Albúmina Sérica Bovina/química , Sulfonamidas/químicaRESUMEN
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.
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INTRODUCTION: Laparoscopic left-sided pancreatectomy (LLP) is an increasingly used surgical technique for the treatment of benign and malignant lesions of the left side of the pancreas. The results of LLP as a treatment for primary pancreatic lesions of the head and tail of the pancreas were evaluated. METHODS: From November 2011 to November 2017, 18 patients underwent surgery for primary lesions of the pancreas by means of a laparoscopic distal pancreatectomy. An intra-abdominal drain tube was used in all cases, and the recommendations of the International Study Group for Pancreatic Fistula (ISGPF) were followed. RESULTS: The mean age was 66.5years (IQR 46-74). Among the 18 left pancreatectomies performed, four were with splenic preservation, and one was a central pancreatectomy. There were two conversions. The median surgical time was 247.5minutes (IQR 242-275). The median postoperative hospital stay was 7days (IQR 6-8). After 90days, complications were detected in five patients: three gradeII, one gradeIII and one gradeV according to the modified Clavien-Dindo classification. There was one gradeB pancreatic fistula, and four patients had to be readmitted to hospital because of peripancreatic collections. The anatomic pathology diagnosis was malignant neoplasm in 38.9% of cases, all of them with negative resection margins. CONCLUSIONS: LLP can be considered the technique of choice in the treatment of primary benign pancreatic lesions and an alternative to the open approach in selected patients diagnosed with malignant pancreatic lesions.