Long-term follow-up of patients with high-risk facial basal cell carcinoma treated with interferon.

BACKGROUND: Surgery is the treatment of choice for patients with basal cell carcinoma (BCC). When surgery is not a choice, only radiotherapy is recommended for patients with high-risk facial BCC. Interferon could be an acceptable therapeutic option for these patients. OBJECTIVE: To evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC. METHODS: Patients with high-risk facial BCC were treated with perilesional injections of alpha-2b+ gamma interferons. Those with incomplete clinical response were reevaluated, their residual tumors excised, and declared cured. Patients treated with interferon and those treated with interferon plus surgery were followed for five years. Time to recurrence and the emergence of a new facial BCC were estimated by Kaplan-Meier survival analysis. Adverse events were documented. RESULTS: This study included 195 participants; 143 (73.3%) showed a complete response (95% CI 67.2‒80.1). Patients developed recurrence after a mean of 55 months (95% CI 53.8‒57.4). The estimated rate of recurrence was 12.3% (95% CI 7.4‒17.1). Patients developed a new BCC after a mean of 52.7 months (95% CI 50.4‒54.9). The estimated rate for development of a new BCC was 20.0% (95% CI 14.4‒25.9). Fifteen (7.7%) patients abandoned the study during follow-up. Adverse events were frequent but moderate or mild; fever and local pain were the most frequent. STUDY LIMITATIONS: Observational cohort design without a control group for comparison. CONCLUSIONS: Perilesional injections of alpha-2b+ gamma interferons in patients with facial high-risk BCC offer a satisfactory cure rate after five years of follow-up with an acceptable safety profile.

Chemistry towards Biology-Instruct: Snapshot.

The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.

Small Molecules Targeting SARS-CoV-2 Spike Glycoprotein Receptor-Binding Domain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic. Several variants of SARS-CoV-2 have emerged worldwide. These variants show different transmissibility infectivity due to mutations in the viral spike (S) glycoprotein that interacts with the human angiotensin-converting enzyme 2 (hACE2) receptor and facilitates viral entry into target cells. Despite the effective SARS-CoV-2 vaccines, we still need to identify selective antivirals, and the S glycoprotein is a key target to neutralize the virus. We hypothesize that small molecules could disrupt the interaction of S glycoprotein with hACE2 and inhibit viral entry. We analyzed the S glycoprotein-hACE2 complex structure (PDB: 7DF4) and created models for different viral variants using visual molecular dynamics (VMD) and molecular operating environment (MOE) programs. Moreover, we started the hits search by performing structure-based molecular docking virtual screening of commercially available small molecules against S glycoprotein models using OEDocking FRED-4.0.0.0 software. The FRED-4.0.0.0 Chemguass4 scoring function was used to rank the small molecules based on their affinities. The best candidate compounds were purchased and tested using a standard SARS-CoV-2 pseudotyped cell-based bioassay to investigate their antiviral activity. Three of these compounds, alone or in combination, showed antiviral selectivity. These small molecules may lead to an effective antiviral treatment or serve as probes to better understand the biology of SARS-CoV-2.

Algal and Cyanobacterial Lectins and Their Antimicrobial Properties.

Lectins are proteins with a remarkably high affinity and specificity for carbohydrates. Many organisms naturally produce them, including animals, plants, fungi, protists, bacteria, archaea, and viruses. The present report focuses on lectins produced by marine or freshwater organisms, in particular algae and cyanobacteria. We explore their structure, function, classification, and antimicrobial properties. Furthermore, we look at the expression of lectins in heterologous systems and the current research on the preclinical and clinical evaluation of these fascinating molecules. The further development of these molecules might positively impact human health, particularly the prevention or treatment of diseases caused by pathogens such as human immunodeficiency virus, influenza, and severe acute respiratory coronaviruses, among others.

Tumor de células granulares: a propósito de un caso / Granulle cell tumor: a case report

RESUMEN Fundamento: el mioblastoma de células granulares también conocido como tumor de Abrikossoff es una neoplasia benigna de rara frecuencia formada por células de aspecto granular. Objetivo: exponer aspectos clínicos del mioblastoma de células granulares. Presentación del caso: se reportó el caso de un paciente masculino de raza negra, 50 años de edad, que fue remitido de la Atención Primaria con impresión clínica de fibroma lingual, al examen bucal se observó lesión ovoide de 3 cm de diámetro en el dorso de la lengua, asintomática, firme, hipocoloreada, consistencia dura y bordes precisos. Se realizó exéresis mediante biopsia escisional. El diagnóstico histopatológico determinó mioblastoma de células granulares. Conclusiones: tanto las características clínicas como histológicas del tumor de células granulares son muy semejantes a otras neoplasias malignas que se asientan en la lengua como el carcinoma epidermoide por tanto su diagnóstico constituye un reto para el estomatólogo.

ABSTRACT Background: granular cell tumor known as Abrikossoff´s tumor is a benign neoplasm of rare incidence formed by cell of granular aspects. Objective: to expose clinical aspects of granular cell tumor. Case report: a clinical case is reported of a 50 years-old black male patient. He was remitted of Primary Health Service with diagnostic impression of tongue's fibroma, in the oral exam was detected an oval lesion of 3cm of diameter on dorsum of the tongue, asymptomatic, firm consistency, and well defined. The lesion was removed by excision biopsy. The histological-pathological study determined a granular cell tumor. Conclusions: both the clinical and histological characteristics of the granular cell tumor are very similar to other malignant neoplasm that settle on the tongue such as epidermoid cell carcinoma therefore its diagnosis constitutes a challenge for the dentistry.

Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs.

Ion channels are macromolecular complexes present in the plasma membrane and intracellular organelles of cells. Dysfunction of ion channels results in a group of disorders named channelopathies, which represent an extraordinary challenge for study and treatment. In this review, we will focus on voltage-gated potassium channels (KV), specifically on the KV4-family. The activation of these channels generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current) and from the somata of hippocampal neurons (ISA). In the heart, KV4 dysfunctions are related to Brugada syndrome, atrial fibrillation, hypertrophy, and heart failure. In hippocampus, KV4.x channelopathies are linked to schizophrenia, epilepsy, and Alzheimer's disease. KV4.x channels need to assemble with other accessory subunits (ß) to fully reproduce the ITO and ISA currents. ß Subunits affect channel gating and/or the traffic to the plasma membrane, and their dysfunctions may influence channel pharmacology. Among KV4 regulatory subunits, this review aims to analyze the KV4/KChIPs interaction and the effect of small molecule KChIP ligands in the A-type currents generated by the modulation of the KV4/KChIP channel complex. Knowledge gained from structural and functional studies using activators or inhibitors of the potassium current mediated by KV4/KChIPs will better help understand the underlying mechanism involving KV4-mediated-channelopathies, establishing the foundations for drug discovery, and hence their treatments.

Hierarchically Imprinted Polymer for Peptide Tag Recognition Based on an Oriented Surface Epitope Approach.

FLAG tag (DYKDDDDK) is a short peptide commonly used for the purification of recombinant proteins. The high price of the affinity columns and their limited reusability are a shortcoming for their widespread use in biotechnology applications. Molecularly imprinted polymers (MIPs) can circumvent some of the limitations of bioaffinity columns for such applications, including long-term stability, reusability, and cost. We report herein the synthesis of MIPs selective to the FLAG tag by hierarchical imprinting. Using the epitope imprinting approach, a 5-amino acid peptide DYKDC was selected as a template and was covalently immobilized on the surface of microporous silica beads, previously functionalized with different aminosilanes, namely, 3-(2-aminoethylamino)propyldimethoxymethylsilane, AEAPMS, and N-(2-aminoethyl)-2,2,4-trimethyl-1-aza-2-silacyclopentane, AETAZS. We investigated the effect of the type of silane on the production of homogeneous silane-grafted layers with the highest extent of silanol condensation as possible using 29Si CP/MAS NMR. We observed that the right orientation of the imprinted cavities can substantially improve analyte recoveries from the MIP. After template and silica removal, the DYKDC-MIPs were used as sorbents for solid-phase extraction (molecularly imprinted solid-phase extraction) of the FLAG peptide, showing that the polymer prepared with AETAZS-bound silica beads contained binding sites more selective to the tag (RMIP-AZA = 87.4% vs RNIP-AZA = 4.1%, n = 3, RSD ≤ 4.2%) than those prepared using AEAPMS (RMIP-DM = 73.4% vs RNIP-DM = 23.2%, n = 3, RSD ≤ 4.0%) as a functionalization agent. An extensive computational molecular modeling study was also conducted, shedding some light on the interaction mechanism between the FLAG peptide and the imprinted template in the binding cavities.

Structural Changes of Sarco/Endoplasmic Reticulum Ca2+-ATPase Induced by Rutin Arachidonate: A Molecular Dynamics Study.

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) maintains the level of calcium concentration in cells by pumping calcium ions from the cytoplasm to the lumen while undergoing substantial conformational changes, which can be stabilized or prevented by various compounds. Here we attempted to clarify the molecular mechanism of action of new inhibitor rutin arachidonate, one of the series of the acylated rutin derivatives. We performed molecular dynamics simulations of SERCA1a protein bound to rutin arachidonate positioned in a pure dipalmitoylphosphatidylcholine bilayer membrane. Our study predicted the molecular basis for the binding of rutin arachidonate towards SERCA1a in the vicinity of the binding site of calcium ions and near the location of the well-known inhibitor thapsigargin. The stable hydrogen bond between Glu771 and rutin arachidonate plays a key role in the binding. SERCA1a is kept in the E2 conformation preventing the formation of important salt bridges between the side chains of several residues, primarily Glu90 and Lys297. All in all, the structural changes induced by the binding of rutin arachidonate to SERCA1a may shift proton balance near the titrable residues Glu771 and Glu309 into neutral species, hence preventing the binding of calcium ions to the transmembrane binding sites and thus affecting calcium homeostasis. Our results could lead towards the design of new types of inhibitors, potential drug candidates for cancer treatment, which could be anchored to the transmembrane region of SERCA1a by a lipophilic fatty acid group.

In silico design and molecular basis for the selectivity of Olinone toward the first over the second bromodomain of BRD4.

Bromodomains (BrDs), a conserved structural module in chromatin-associated proteins, are well known for recognizing ε-N-acetyl lysine residues on histones. One of the most relevant BrDs is BRD4, a tandem BrD containing protein (BrD1 and BrD2) that plays a critical role in numerous diseases including cancer. Growing evidence shows that the two BrDs of BRD4 have different biological functions; hence selective ligands that can be used to study their functions are of great interest. Here, as a follow-up of our previous work, we first provide a detailed characterization study of the in silico rational design of Olinone as part of a series of five tetrahydropyrido indole-based compounds as BRD4 BrD1 inhibitors. Additionally, we investigated the molecular basis for Olinone's selective recognition by BrD1 over BrD2. Molecular dynamics simulations, free energy calculations, and conformational analyses of the apo-BRD4-BrD1|2 and BRD4-BrD1|2/Olinone complexes showed that Olinone's selectivity is facilitated by five key residues: Leu92 in BrD1|385 in BrD2 of ZA loop, Asn140|433, Asp144|His437 and Asp145|Glu438 of BC loop, and Ile146|Val49 of helix C. Furthermore, the difference in hydrogen bonds number and in mobility of the ZA and BC loops of the acetyl-lysine binding site between BRD4 BrD1/Olinone and BrD2/Olinone complexes also contribute to the difference in Olinone's binding affinity and selectivity toward BrD1 over BrD2. Altogether, our computer-aided molecular design techniques can effectively guide the development of small-molecule BRD4 BrD1 inhibitors, explain their selectivity origin, and further open doors to the design of new therapeutically improved derivatives.

Carcinoma epidermoide de seno maxilar: a propósito de un caso / Squamous cell carcinoma of the maxillary sinus: a case report

RESUMEN Fundamento: el carcinoma epidermoide de seno maxilar es de poca frecuencia, capaz de provocar compromiso estético-funcional por lo que su diagnóstico temprano permitirá al paciente un mejor pronóstico. Objetivo: exponer aspectos clínicos del carcinoma epidermoide de seno maxilar. Caso clínico: paciente masculino de raza blanca, 64 años de edad, con aumento de volumen en región orbito-cigomática izquierda de un mes de evolución. La tomografía axial computarizada de senos paranasales reveló imagen heterogénea sugestiva de tumor de seno maxilar del lado izquierdo. El diagnóstico histopatológico reportado fue de carcinoma epidermoide bien diferenciado. Se instauró el tratamiento con quimioterapia y radioterapia concurrente. El motivo de mostrar este caso consiste en aportar experiencias que permitan el diagnóstico temprano de la enfermedad y así mejorar el pronóstico para el paciente. Conclusiones: un examen clínico minucioso conducirá a un diagnóstico precoz de estas enfermedades que presentan una evolución tórpida y carecen de signos patognomónicos sobre todo en sus estadios iniciales. Es de vital importancia el papel protagónico que tiene la Atención Primaria de Salud para la detección del cáncer el cual constituye una de las primeras causas de muerte en Cuba.

ABSTRACT Background: squamous cell carcinomas of maxillary sinus are rare. It causes esthetic-functional compromise. Therefore, its early diagnosis will allow the patient better prognosis. Objective: to expose clinical aspects of squamous cell carcinoma in maxillary sinus. Case report: a clinical case is reported from 64-year-old white male patient with swelling over the orbit-zygomatic area that progressed over 1 month. The paranasal sinus CAT scan showed a heterogenic image suggesting a left maxillary tumor. The histopathological diagnosis reported a well- differentiated squamous cell carcinoma. Chemotherapy and radiotherapy can be used in this case. The scope of showing this case is to provide some aspects that allow the early diagnosis of the aforementioned disease as well as to improve the patients' prognosis. Conclusions: the deep clinical examination in patients will allow a soon diagnosis of these pathologies that present a torpid evolution lacking pathognomonic signs mainly in first stages. It is of paramount importance the role of the Primary Health Service in the early detection of cancer, which constitutes one of the main causes of death in Cuba.

Estudio clínico-epidemiológico de pacientes con cáncer en suelo de boca / Clinical-epidemiological study of patients with cancer in the mouth floor

RESUMEN Fundamento: el suelo de boca es constituido solo por tejidos blandos y carentes de planos de referencia ósea; representa una de las regiones más delicadas de la cavidad oral. En este sitio anatómico es frecuente la aparición de neoplasias malignas, las que motivan consultas médicas, cirugías, tratamientos oncológicos y muertes. Objetivo: caracterizar a la población con cáncer en suelo de boca en cuanto a las variables sociodemográficas: edad, sexo, presencia de factores de riesgo, síntomas clínicos de la enfermedad y las características anatomoclínicas de la lesión. Método: se realizó un estudio descriptivo y retrospectivo de 7 años en la población, objeto de estudio que asistió a la consulta de Cirugía Maxilofacial del Hospital Oncológico María Curie de Camagüey, desde enero de 2011 hasta enero de 2018. El estudio incluyó un total de 34 pacientes con diagnóstico de cáncer en suelo de boca, basado en un interrogatorio, examen físico y biopsia. Resultados: hubo mayor incidencia en el grupo de edad de 60-69 años (41,17 %) y predominó el sexo masculino (76,47 %). Los factores de riesgo con mayores valores fueron el tabaquismo (73,52 %) y alcoholismo (38,23 %).Dentro de las manifestaciones clínicas el dolor fue la sintomatología más común y predominaron las lesiones del tipo ulceradas (35,29 %). Conclusiones: predominaron las edades por encima de los 60 años al igual que el sexo masculino, la población mostró una adicción marcada al tabaquismo y al alcoholismo, el dolor constituyó el principal síntoma en la primera consulta, las lesiones del tipo ulceradas fueron las más frecuentes.

ABSTRACT Background: the floor of the mouth constituted only by soft tissues and lacking of plans of osseous reference represents one of the most delicate areas of the oral cavity. The appearance of malignat neoplasias is frequently seen in this anatomic site which is the cause of medical consultations, surgeries, oncologic treatments and deaths. Objective: to characterize the population of patients with cancer on the floor of the mouth based on the sociodemographic variables such as age, sex, riskfactors, clinical symptoms of the disease and anatomic-pathological characteristics of the lesion. Methods: A descriptive and observational retrospective study during 7 years was carried out in the object of study population, which attended the Maxillofacial Surgery Consultation at Maria Curie Oncologic Hospital from January 2011 to January 2018. The study included 34 patients diagnosed with cancer on the floor of the mouth based on the interview, the physical examination and the biopsy. Results: There was a great incidence in the age groups between 60 and 69 years old (41,17 %), belonging to the male sex (76,47 %).The most common risk factors were nicotine (73,52 %) and alcoholism (38,23 %). Among the clinical manifestations, the pain was the most common clinical symptom and there was a prevalence of ulcerative lesions (35.29 %). Conclusions: There was a prevalence in the age groups older than 60 years old and male sex,the population showed a marked nicotine and alcohol addiction. The pain was the main symptom in the first consultation and there was a prevalence of ulcerative lesions.

A Solid-Phase Approach to Accessing Bisthioether-Stapled Peptides Resulting in a Potent Inhibitor of PRC2 Catalytic Activity.

Stapled peptides have emerged as a new class of therapeutics to effectively target intractable protein-protein interactions. Thus, efficient and versatile methods granting easy access to this class of compounds and expanding the scope(s) of the currently available ones are of great interest. Now, a solid phase approach is described for the synthesis of bisthioether stapled peptides with multiple architectures, including single-turn, double-turn, and double-stapled macrocycles. This method allows for ligation with all-hydrocarbon linkers of various lengths, avoiding the use of unnatural amino acids and expensive catalysts, and affords cyclopeptides with remarkable resistance to proteolytic degradation. The potential of this procedure is demonstrated by applying it to generate a stapled peptide that shows potent in vitro inhibition of methyltransferase activity of the polycomb repressive complex 2 (PRC2) of proteins.

Modulating Mineralocorticoid Receptor with Non-steroidal Antagonists. New Opportunities for the Development of Potent and Selective Ligands without Off-Target Side Effects.

Steroidal mineralocorticoid receptor (MR) antagonists are used for treatment of a range of human diseases, but they present challenging issues of complex chemical synthesis, undesirable physical properties, and poor selectivity along with unwanted side effects. Therefore, there is a great interest in the discovery of non-steroidal ligands able to bind to the ligand-binding domain of the MR and recruit different co-regulators to produce tissue-specific therapeutic effects. Several academic groups and pharmaceutical companies have been developing a series of non-steroidal ligands that consist of different chemical scaffolds, yielding MR antagonists currently evaluated in clinical studies for the treatment of congestive heart failure, hypertension, or diabetic nephropathy. The main focus of this Perspective is to review the reported structure-activity relationships of the different series of compounds, as well as the structural studies that contribute to a better understanding of the receptor active site and are also helpful for optimization processes.

EYA1's Conformation Specificity in Dephosphorylating Phosphothreonine in Myc and Its Activity on Myc Stabilization in Breast Cancer.

EYA1 is known to be overexpressed in human breast cancer, in which the Myc protein is also accumulated in association with decreased phospho-T58 (pT58) levels. We have recently reported that EYA1 functions as a unique protein phosphatase to dephosphorylate Myc at pT58 to regulate Myc levels. However, it remains unclear whether EYA1-mediated Myc dephosphorylation on T58 is a critical function in regulating Myc protein stability in breast cancer. Furthermore, EYA1's substrate specificity has remained elusive. In this study, we have investigated these questions, and here, we report that depletion of EYA1 using short hairpin RNA (shRNA) in breast cancer cells destabilizes the Myc protein and increases pT58 levels, leading to an increase in the doubling time and impairment of cell cycle progression. In correlation with EYA1-mediated stabilization of cMyc and reduced levels of pT58, EYA1 greatly reduced cMyc-FBW7 binding and cMyc ubiquitination, thus providing novel insight into how EYA1 acts to regulate the FBW7-mediated Myc degradation machinery. We found that the conserved C-terminal haloacid dehalogenase domain of EYA1, which has been reported to have only tyrosine phosphatase activity, has dual phosphatase activities, and both the N- and C-terminal domains interact with substrates to increase the catalytic activity of EYA1. Enzymatic assay and nuclear magnetic resonance (NMR) analysis demonstrated that EYA1 has a striking conformation preference for phospho-T58 of Myc. Together, our results not only provide novel structural evidence about the conformation specificity of EYA1 in dephosphorylating phosphothreonine in Myc but also reveal an important mechanism contributing to Myc deregulation in human breast cancer.

Structure-Guided Discovery of Selective Antagonists for the Chromodomain of Polycomb Repressive Protein CBX7.

The chromobox 7 (CBX7) protein of the polycomb repressive complex 1 (PRC1) functions to repress transcription of tumor suppressor p16 (INK4a) through long noncoding RNA, ANRIL (antisense noncoding RNA in the INK4 locus) directed chromodomain (ChD) binding to trimethylated lysine 27 of histone H3 (H3K27me3), resulting in chromatin compaction at the INK4a/ARF locus. In this study, we report structure-guided discovery of two distinct classes of small-molecule antagonists for the CBX7ChD. Our Class A compounds, a series including analogues of the previously reported MS452, inhibit CBX7ChD/methyl-lysine binding by occupying the H3K27me3 peptide binding site, whereas our Class B compound, the newly discovered MS351, appears to inhibit H3K27me3 binding when CBX7ChD is bound to RNA. Our crystal structure of the CBX7ChD/MS351 complex reveals the molecular details of ligand recognition by the aromatic cage residues that typically engage in methyl-lysine binding. We further demonstrate that MS351 effectively induces transcriptional derepression of CBX7 target genes, including p16 (INK4a) in mouse embryonic stem cells and human prostate cancer PC3 cells. Thus, MS351 represents a new class of ChD antagonists that selectively targets the biologically active form of CBX7 of the PRC1 in long noncoding RNA- and H3K27me3-directed gene transcriptional repression.

Small-molecule modulators of methyl-lysine binding for the CBX7 chromodomain.

Chromobox homolog 7 (CBX7) plays an important role in gene transcription in a wide array of cellular processes, ranging from stem cell self-renewal and differentiation to tumor progression. CBX7 functions through its N-terminal chromodomain (ChD), which recognizes trimethylated lysine 27 of histone 3 (H3K27me3), a conserved epigenetic mark that signifies gene transcriptional repression. In this study, we report the discovery of small molecules that inhibit CBX7ChD binding to H3K27me3. Our crystal structures reveal the binding modes of these molecules that compete against H3K27me3 binding through interactions with key residues in the methyl-lysine binding pocket of CBX7ChD. We further show that a lead compound, MS37452, derepresses transcription of Polycomb repressive complex target gene p16/CDKN2A by displacing CBX7 binding to the INK4A/ARF locus in prostate cancer cells. These small molecules have the potential to be developed into high-potency chemical modulators that target CBX7 functions in gene transcription in different disease pathways.

Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression.

Lysine acetylation regulates gene expression through modulating protein-protein interactions in chromatin. Chemical inhibition of acetyl-lysine binding bromodomains of the major chromatin regulators BET (bromodomain and extraterminal domain) proteins has been shown to effectively block cell proliferation in cancer and inflammation. However, whether selective inhibition of individual BET bromodomains has distinctive functional consequences remains only partially understood. In this study, we show that selective chemical inhibition of the first bromodomain of BET proteins using our small-molecule inhibitor, Olinone, accelerated the progression of mouse primary oligodendrocyte progenitors toward differentiation, whereas inhibition of both bromodomains of BET proteins hindered differentiation. This effect was target specific, as it was not detected in cells treated with inactive analogs and independent of any effect on proliferation. Therefore, selective chemical modulation of individual bromodomains, rather than use of broad-based inhibitors, may enhance regenerative strategies in disorders characterized by myelin loss such as aging and neurodegeneration.

Manejo de las lesiones de la vía biliar postcolecistectomía laparoscópica mediante colangiopancreatografía retrógrada endoscópica / Management of post-cholecystectomy bile duct injuries under endoscopic retrograde cholangiopancreatography

Introducción: la colecistectomía laparoscópica ha sustituido a la cirugía convencional por sus múltiples ventajas, pero se asocia a un incremento en la incidencia de lesiones de la vía biliar, para las cuales, entre los diferentes enfoques terapéuticos, la opción de la colangiopancreatografía retrógrada endoscópica constituye una herramienta fundamental. Objetivo: describir una serie de casos con lesiones postquirúrgicas de la vía biliar manejados mediante colangiopancreatografía retrógrada endoscópica. Métodos: se efectuó un estudio descriptivo, transversal en pacientes que se les realizó la colangiopancreatografía retrógrada endoscópica en el periodo comprendido desde 23 de febrero del 2010 hasta el 30 de noviembre del 2013, quedando conformada la población de estudio por 13 pacientes con diagnóstico de lesión de la vía biliar post-colecistectomía laparoscópica. Se analizaron las siguientes variables: edad, sexo, tipo de lesión, coledocolitiasis asociada, tratamiento, resultados del tratamiento y complicaciones. Las lesiones se clasificaron según la clasificación de Ámsterdam. Las fugas además se clasificaron en de alto grado y bajo grado. Resultados: predominó el sexo femenino y la edad media de los pacientes fue de 49,9 años. La lesión más frecuente fue la tipo A asociada a coledocolitiasis, solucionándose mediante esfinterotomía endoscópica y extracción de cálculos. Solamente un caso presentó complicación post-CPRE y no hubo mortalidad. Conclusiones: la introducción de la colangiopancreatografía retrógrada endoscópica en la provincia de Matanzas ha permitido utilizarla como una herramienta útil en el manejo de las lesiones de la vía biliar secundarias a colecistectomía laparoscópica.

Introduction: laparoscopic cholecystectomy has replaced traditional cholecystectomy due to its multiple advantages, however it is associated to the increase of bile duct injury against which the option of endoscopic retrograde cholangiopancreatography is a main tool, among different therapeutic approaches. Objective: to describe a series of cases with postsurgical bile duct injuries managed by endoscopic retrograde cholangiopancreatography.Methods: It was performed a descriptive, cross-sectional study on patients treated by endoscopic retrograde cholangiopancreatography from February 23rd 2010 up to November 30th 2013, being the study population 13 patients with a diagnose of post laparoscopic cholecystectomy bile duct injury. The following variables were analyzed: age, gender, kind of injury, associated choledocholithiasis, treatment, treatment results and complications. Injuries were classified according to Amsterdam classification. Leakages were also classified as high and low degree. Results: female genre prevailed and the patients mean age was 49,9. The most frequent injury was type A, associated to choledocholithiasis which was solved by endoscopic sphincterotomy and stones removal. There was only one case with post ERCP complications, without mortality.Conclusions: the introduction of endoscopic retrograde cholangiopancreatography in Matanzas province has allowed using it as a helpful tool in the treatment of bile duct injuries resulting from laparoscopic cholecystectomy.

Colangiopancreatografía Retrógrada Endoscópica en un hospital de nivel secundario / Endoscopic Retrograde Cholangiopancreatography in a secondary level hospital

Introducción: se introduce la colangiopancreatografía retrógrada endoscópica en la provincia de Matanzas en el año 2010 como complemento de un servicio de Cirugía de Mínimo Acceso con años de experiencia. Objetivo: describir nuestros resultados en 3 años de trabajo. Métodos: se realizó un estudio descriptivo, transversal en pacientes que se realizaron la colangiopancreatografía retrógrada endoscópica en el servicio de Cirugía de Mínimo Acceso del Hospital Universitario Clínico-Quirúrgico Comandante Faustino Pérez Hernández de Matanzas en el periodo comprendido desde 23 de febrero del 2010 hasta el 23 febrero del 2013. Aplicados los criterios de inclusión y exclusión, la población de estudio quedó constituida por 240 pacientes en los que se realizaron 269 procederes. Se analizaron variables demográficas, variables relacionadas con aspectos técnicos, y variable clínicas. Resultados: predominó el sexo femenino con 61,25 por ciento de los pacientes. El grupo etario más frecuente fue de 56 a 65 años con 22,91 por ciento. La efectividad en la canulación del conducto deseado fue del 91,67 por ciento, realizándose precorte solo en 4,16 por ciento. Resultó ser el diagnóstico más frecuente (35,74 por ciento) la litiasis coledociana. El 85,94 por ciento de los procederes requirió intervención terapéutica. Se presentaron complicaciones en 7,43 por ciento de las CPRE y la más frecuente fue la colangitis aguda (3,34 por ciento). La mortalidad fue de 1,86 por ciento. Conclusiones: los resultados de este estudio son similares a los de otros centros nacionales e internacionales, considerándose la CPRE un proceder seguro en nuestro medio.

Introduction: the endoscopic retrograde cholangiopancreatography is introduced in Matanzas province in 2010 as complement to a Minimum Access Surgery service with several years of experience. Objective: to describe our results during three years of work.Methods: a descriptive, cross section study was carried out on patients treated with the endoscopic retrograde cholangiopancreatography (ERCP) in the Minimum Access Surgery service at Matanzas Comandante Faustino Pérez Hernández Clinical-Surgical University Hospital during the period February 23rd 2010- February 23rd 2013. Applying inclusion and exclusion criteria the sample was made up of 240 patients in which 269 procedures were carried out. Demographic variables, variables related to technical aspects, as well as clinical variables were analyzed. Results: female prevailed with 61,25 percent of the patients. The most frequent age bracket was 56 to 65 years with 22,91 percent.The effectiveness in the cannulation of the desired duct was 91,67 per cent carrying out precut only in 4,16 percent. The most frequent diagnosis was choledocholithiasis (35,74 percent). 85,94 percent of the procedures required therapeutic operation. There were complications in 7,43 percent of the endoscopic retrograde cholangiopancreatographies and the most frequent complication was acute cholangitis (3,34 percent). Mortality was 1,86 percent. Conclusions: the results of our study are similar to those from other national and international health centers, considering the endoscopic retrograde cholangiopancreatography a safe procedure in our environment.

Síndrome de Mirizzi tipo IV: diagnóstico y manejo mediante colangiopancreatografía retrógrada endoscópica: reporte de caso / Mirizzi Syndrome Type IV: diagnosis and management through retrograde endoscopic cholangiopancreatography: case report

El síndrome de Mirizzi es una rara complicación de la colelitiasis, caracterizado por obstrucción mecánica del conducto hepatocolédoco por un cálculo impactado en el cístico o en el cuello vesicular. Después de un período de tiempo puede desarrollarse una fístula colecistobiliar por destrucción de la pared del colédoco. Según la clasificación de Csendes, el tipo IV es el menos frecuente. Se presentó un caso con antecedente de colelitiasis que ingresa con cuadro clínico compatible con colangitis aguda. Se realiza CPRE electiva, diagnosticándose síndrome de Mirizzi tipo IV y se coloca prótesis como puente para el tratamiento quirúrgico. Ante un paciente con esas características, la CPRE resulta un método diagnóstico y terapéutico indispensable.

The Mirizzi syndrome is a cholelithiasis rare complication, characterized by the mechanical obstruction of the hepato choledocus duct by a calculus impacted in the cystic or in the vesicular neck. We presented a case with cholelithiasis antecedents entering the hospital with a clinical picture compatible with acute cholangitis. We made an elective cholangiopancreatography finding a big protraction of the intrahepatic biliary tracts, stretch of the supraduodenal choledoc with a common cystic-vesicular neck and choledocian environment, forming a great duct of near 20 mm diameter, having inside an ovoid filling mistake which bigger diameter is 15 mm, directed to the choledocus and to the vesicle. We diagnosed a Mirizzi syndrome Type IV. In a patient with those characteristics, the cholangiopancreatography is an unavoidable diagnostic and therapeutic method.