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<b>Introduction:</b> Computer-based interactive techniques are becoming an important tool in medical education. One of the important benefits of the use of telemedicine in surgical training is the reduction of the number of people in the operating room. As shown in the studies, this can lead i.a. to the reduction in the risk of surgical site infections.<b>Aim:</b> The aim of this survey as held among fifth-year medical students at three academic centers was to assess the usefulness and effectiveness of telemedicine as a surgery-teaching tool.<b>Material and methods:</b> A transmission of a surgical procedure was carried out by each of the three participating centers according to a previously prepared schedule. Each transmission was preceded by the diagnostics, indications, and the course of the surgical procedure being discussed by the facilitator physician who also coordinated the transmission throughout the procedure. After the class, students received anonymous surveys consisting of fourteen questions as per the attached protocol so as to evaluate the class using the rating scale of 1 (the lowest rating) through 5 (the highest rating). The survey assessed the educational value (the knowledge acquired from the class), the form (interactivity, facilitator complicity), and the usefulness of the class for overall surgical education.<b>Results:</b> The survey was completed by 232 students, with 95% of respondents rating the usefulness of telemedicine classes in surgical education as very good or good. As many as 97% of students declared that the transmission had been a good or a very good tool in terms of delivery or adding to their knowledge of topographical anatomy and basic aspects of surgical technique. Higher ratings were given to the usefulness of comments and remarks by the facilitating physician (96% of very good or good ratings) who had been watching the procedure along with the students as compared to those provided by the operating physician (81%).<b>Discussion:</b> The use of telemedicine-based teaching models in surgical education facilitates a better view of the operating field for the students, greater accessibility of educational content delivered simultaneously to multiple groups of students, increased safety of the surgical procedure by reducing the number of people in the operating room as well as reduced burden on the operating physician (thanks to the introduction of class facilitator).<b>Conclusions:</b> In our opinion, the advantages of the presented teaching model are: better view (particularly in case of open procedures), ability to pinpoint surgical field structures (on the participants' and operator's monitors), absence of additional people (students) in the operating room (increasing the safety of the procedure and reducing the risk of surgical site infections) and the ability to go back to recorded operations and perform various types of educational analyses.
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Estudiantes de Medicina , Telemedicina , Humanos , Polonia , Estudiantes de Medicina/estadística & datos numéricos , Encuestas y Cuestionarios , Masculino , Femenino , Cirugía General/educación , Competencia Clínica , Educación de Pregrado en Medicina/métodos , AdultoRESUMEN
One of the target of perioperative tratment in surgery is decreasing intraoperative bleeding, which increases the number of perioperative procedures, mortality and treatment costs, and also causes the risk of transfusion of blood and its components. Trying to minimize the blood loss(mainly during the operation) as well as the need to transfuse blood and its components (broadly understood perioperative period) should be standard treatment for a patient undergoing a procedure. In the case of this method, the following steps should be taken: 1) in the preoperative period: identyfication of risk groups as quickly as possible, detecting and treating anemia, applying prehabilitation, modyfying anticoagulant treatment, considering donating one's own blood in some patients and in selected cases erythropoietin preparations; 2) in the perioperative period: aim for normothermia, normovolemia and normoglycemia, use of surgical methods that reduce bleeding, such as minimally invasive surgery, high-energy coagulation, local hemostatics, prevention of surgical site infection, proper transfusion of blood and its components if it occurs; 3) in the postoperative period: monitor the condition of patients, primarily for the detection of bleeding, rapid reoperation if required, suplementation (oral administration preferred) nutrition with microelements (iron) and vitamins, updating its general condition. All these activities, comprehensively and in surgical cooperation with the anesthesiologist, should reduce the blood loss and transfusion of blood and its components.
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Anemia , Hemostáticos , Humanos , Hemorragia , Transfusión Sanguínea/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
Introduction: Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. Aim: The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. Material and methods: The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. The recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. Results and conclusions: There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The second part of the guidelines covers sections 6 to12 and the following challenges for surgical practice: acute appendicitis, acute mesenteric ischemia, abdominal injuries, bowel obstruction, diverticulitis, laparoscopy in pregnancy and postoperative complications requiring a reoperation.
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Introduction: Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. Aim: The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. Material and methods: The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. Results and conclusions: There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The first part of the guidelines covers 5 sections and the following challenges for surgical practice: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia and acute cholecystitis. Contraindications for laparoscopy and the ERAS program are discussed.
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Colorectal cancer (CRC) is the second most common cause of cancer-related death globally. Because of a tendency to be an asymptomatic primary tumor and therefore resulting in late detection, most CRC patients are diagnosed in the advanced stage. Several miRNAs have the potential to become novel noninvasive biomarkers measured as diagnostic and prognostic indicators of CRC to guide surgical therapies and promote the understanding of the carcinogenesis of CRC. Since the change of miR-3613-3p was associated with several types of cancer other than colorectal cancer, there is a lack of functional evidence and the results are inconsistent. We conducted a pilot microarray study in which we noted a decreased expression of miR-3613-3p in colorectal cancer cells, then we confirmed the expression of miR-3613-3p by qPCR on a group of 83 patients, including 65 patients with colorectal cancer, 5 with a benign tumor and 13 from the control group. We noted that in both malignant and benign tumors, miR-3613-3p is downgraded relative to the surrounding tissue. As a result of the study, we also observed colorectal tumor tissue and surrounding tissue in patients with colorectal cancer who received radiotherapy before surgery, which showed a significantly higher expression of miR-3613-3p compared to patients who did not receive radiotherapy. In addition, we noted that the tissue surrounding the tumor in patients with distant metastases showed a significantly higher expression of miR-3613-3p compared to patients without distant metastases. The increased expression of miR-3613-3p in patients after radiotherapy suggests the possibility of using this miR as a therapeutic target for CRC, but this requires confirmation in further studies.
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Neoplasias Colorrectales , MicroARNs , Oncología por Radiación , Humanos , MicroARNs/genética , Carcinogénesis , Neoplasias Colorrectales/genéticaRESUMEN
PURPOSE: Multimodal treatment is the standard of care in patients with locally advanced gastric cancer. Unfortunately, the response rate after neoadjuvant treatment remains limited. The ability to predict the response has a potential to improve patient outcomes by promoting a more individualized approach. We sought to describe the current state of research in pre-treatment molecular biomarkers of response to neoadjuvant therapy in gastric adenocarcinoma available for testing before the initiation of treatment and to perform a systematic review and meta-analysis in order to summarize and evaluate the potential methods. METHODS: A systematic MEDLINE, EMBASE and CENTRAL literature search was conducted to extract articles on potentially predictive molecular biomarkers of pathological response to neoadjuvant therapy in patients with gastric- and esophago-gastric junction adenocarcinoma. Fixed and random effects models were used to undertake the meta-analysis when appropriate. RESULTS: Data on predictive biomarkers was reported in 38 studies. These articles described 47 biomarkers showing statistical significance. After evaluation of all reported biomarkers, 3 of them met the inclusion criteria for meta-analysis. The meta-analysis results indicate that >5 âng/mL pre-therapeutic serum concentration of carcinoembryonic antigen (CEA; norm <5 âng/mL) is significantly associated with tumor response (RR â= â5.13, 95% CI 2.53-10.43, P â= â0.026). CONCLUSION: Previous studies describe a large number of candidate biomarkers. Our meta-analysis indicated pre-therapeutic serum concentration of CEA >5 âng/mL as a potential and easy-accessible biomarker available for use before initiation of treatment. However, it could be only an additional tool for complex qualification for neoadjuvant therapy.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Terapia Neoadyuvante/métodos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Antígeno Carcinoembrionario/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patologíaRESUMEN
INTRODUCTION: Correct surgical technique and perioperative care are two factors that can reduce the number of complications, improve treatment outcomes and shorten the length of hospital stay. The introduction of enhanced recovery protocols has changed the approach to patient care in some centers. However, there are significant differences among centers, and in some the standard of care has remained unchanged. AIM: the goal of the panel was to develop recommendations for modern perioperative care in accordance with current medical knowledge in order to reduce the number of complications associated with surgical treatment. An additional goal was to optimize and standardize perioperative care among Polish centers. MATERIALS AND METHODS: the development of these recommendations was based on a review of the available literature from the PubMed, Medline and Cochrane Library databases from January 1, 1985 to March 31, 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations were formulated in a directive form and were assessed using the Delphi method. RESULTS AND CONCLUSIONS: 34 recommendations for perioperative care were presented. They cover aspects of pre-, intra- and post-operative care. Implementation of the presented rules allows to improve the results of surgical treatment.
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Procedimientos Quirúrgicos Electivos , Atención Perioperativa , Humanos , Consenso , Atención Perioperativa/métodos , Complicaciones Posoperatorias , Tiempo de InternaciónRESUMEN
BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. METHODS: A total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). RESULTS: The 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. CONCLUSIONS: A clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.
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Nomogramas , Neoplasias Gástricas , Humanos , Pronóstico , Estadificación de Neoplasias , Neoplasias Gástricas/patología , Ganglios Linfáticos/patologíaRESUMEN
<b><br>Introduction:</b> Neoadjuvant chemotherapy (NAC) is a part of the current standard of care in a locally advanced gastric adenocarcinoma (GA) and esophagogastric junction adenocarcinoma (EGJA), but only patients with good pathomorphological response (pR) to NAC benefit from prolonged overall survival.</br> <b><br>Aim:</b> The study aims to evaluate ApoA-I and ApoB as candidate pre-treatment biomarkers of pR to NAC in patients with GA and EGJA.</br> <b><br>Materials and methods:</b> Serum samples were collected from 18 patients with GA and 9 with EGJA before the initiation of NAC to determine the ApoA-I and ApoB levels. After NAC tumor regression grade (TRG) was evaluated in resected specimens according to the Mandard's tumor regression grading system and correlated with pre-treatment ApoA-I and ApoB serum concentration, and ApoB-to-ApoA-I serum concentration ratio.</br> <b><br>Results:</b> We found a positive correlation of ApoA-I level and pR (95% CI: -0.863 to -0.467; P < 0.0001), a negative correlation of ApoB level and pR (95% CI: 0.445 to 0.857; P < 0.0001), a negative correlation of ApoB-to-ApoA-I ratio and pR (95% CI: 0.835 to 0.964; P < 0.0001).</br> <b><br>Conclusions:</b> ApoA-I and ApoB levels, and ApoB-to-ApoA-I ratio are candidate pre-treatment predictors of pR to NAC in GA and may help to guide personalized therapy.</br>Our work fits into the dynamically developing trend of personalized treatment. It describes a potentially important rationale for further evaluation of apolipoprotein A-I and apolipoprotein B as predictors of cancer response to neoadjuvant therapy.
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Adenocarcinoma , Apolipoproteína A-I , Apolipoproteínas B , Biomarcadores , Neoplasias Gástricas , Humanos , Adenocarcinoma/tratamiento farmacológico , Apolipoproteína A-I/análisis , Apolipoproteínas B/análisis , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
Surgical procedures are extremely burdensome for patients, as in addition to complications directly related to the intervention, they expose the patient to further complications resulting from the disturbance of key functions of homeostasis in the body's systems, particularly the circulatory, respiratory, and nervous systems. Furthermore, they may contribute to the exacerbation of symptoms of underlying chronic diseases. This paper focuses on the most common possible neurological complications that may occur after surgical procedures and includes topics such as stroke, chronic pain, neuropathy, and delirium. The risk factors for neurological deficits, their known or possible etiology, the most characteristic symptoms, and potential preventive actions are discussed. The paper analyzes articles from the PubMed, ResearchGate, and Scopus databases. A surge0on's knowledge of possible complications that may occur in the perioperative period enables early recognition and effective reduction of their negative impact on the patient's functioning and quality of life after surgery, contributing to better overall treatment outcomes.
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Complicaciones Posoperatorias , Calidad de Vida , Humanos , Resultado del Tratamiento , Factores de Riesgo , Periodo Perioperatorio , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
This document - "Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022" - represents an expert consensus following a year's worth of dedicated effort by a team of specialists throughout 2021, put forward in a conference in December 2021 in Krakow, and finalized below for publication in 2022. The effective date of this document is June 14th 2022. The work that went into updating this consensus was made under auspices of the Polish Society of Surgical Oncology and the Association of Polish Surgeons.
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Neoplasias Gástricas , Consenso , Humanos , Polonia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapiaRESUMEN
Over the years, the rise in the obesity epidemic has led to an increasing demand for bariatric surgery. Considering the rapidly growing number of bariatric surgery procedures performed, intensive development of postoperative care and surveillance programs should be expected. However, the effectiveness of follow-up after bariatric surgery appears to be surprisingly low. The purpose of this review is to draw attention to the quality of follow-up programs and to encourage health care providers to make efforts to ensure adequate post-operative data collection. Awareness should be raised about inadequate data collection to strengthen the credibility and authenticity of treatment results, thus providing a clearer picture of treatment efficacy.
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The COVID-19 (coronavirus disease 2019) pandemic has markedly affected the life of people worldwide. In Poland, one of its consequences consisted in new laws being put into force to regulate the provision of healthcare services. This gave rise to much anxiety and concern within the healthcare community, particularly among the specialists in interventional medicine. Taking into account all signals received by the National Consultant, Voivodeship Consultants, as well as the Association of Polish Surgeons and the Polish Chamber of Physicians and Dentists, the new regulations negatively affect the performance of healthcare professionals, e.g. in the context of diagnostic and therapeutic decision-making or activities potentially beneficial for patients not being undertaken. The authors of the article have analyzed the regulations in force in an attempt to bring their interpretation into line with their substance and their objective, as well as to provide comprehensive answers to questions and concerns as raised by interventional surgeons.
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COVID-19 , Criminales , Cirujanos , Atención a la Salud , Humanos , Pandemias , SARS-CoV-2RESUMEN
The paper was prepared by an expert group appointed by the Polish Society of Gastroenterology with an aim to update and systematize the knowledge about diagnosis and treatment of gastroesophageal reflux disease (GERD). Based on the previously published guidelines of international societies, expert consensuses, and recently published good quality data, we formulated 74 statements regarding the definition, diagnosis and treatment of GERD and assessed the level of acceptance of these statements and the reliability of the data. We discussed in details the possibilities and limitations of the available diagnostic methods and therapies, with particular emphasis on the diversity of gastroesophageal reflux symptoms and complications including Barrett's esophagus. Practical principles regarding interpretation of the diagnostic tests are presented. In addition, we discussed the indications for surgical treatment as well as the situations in which surgical treatment is not indicated with emphasis on the importance of preoperative diagnostics. The role of add-on therapy and indications for maintenance treatment are defined.
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Gastroenterología , Reflujo Gastroesofágico , Consenso , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/terapia , Humanos , Polonia , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Gastrointestinal fistula is one of the most difficult problems in gastrointestinal surgery. It is associated with high morbidity and mortality, numerous complications, prolonged hospitalization, and high cost of treatment. AIM: This project aimed to develop recommendations for the treatment of gastrointestinal fistulas, based on evidence-based medicine and best clinical practice to reduce treatment-related mortality and morbidity. MATERIAL AND METHODS: The preparation of these recommendations is based on a review of the literature from the PubMed, Medline, and Cochrane Library databases from 1.01.2010 to 31.12.2020, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations in the form of a directive were formulated and assessed using the Delphi method. RESULTS AND CONCLUSIONS: Nine recommendations were presented along with a discussion and comments of experts. Treatment should be managed by a multidisciplinary team (surgeon, anesthetist, clinical nutritionist/dietician, nurse, pharmacist, endoscopist).
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Procedimientos Quirúrgicos del Sistema Digestivo , Fístula , Medicina Basada en la Evidencia , Humanos , Polonia , Guías de Práctica Clínica como AsuntoRESUMEN
Perianal fistulas in Crohn's disease (CD) are a major problem. In majority of patient, inflammation involves the rectum. Perianal fistulas in CD pose a diagnostic and therapeutic challenge due to severe symptoms and worse prognosis compared to cryptogenic fistulas. The accurate diagnosis is crucial for an effective treatment of CD-related perianal fistulas, and the following should be determined: anatomy of the fistula, possible strictures and inflammation of the alimentary tract, including the rectum and the anal canal. Treatment of fistulas might be challenging and requires cooperation between the colorectal surgeon and the gastroenterologist. The combination of surgical and pharmacological therapy is more effective than surgical or pharmacological therapy alone. In conservative treatment, aminosalicylates or steroids have little significance. In everyday practice, antibacterial chemotherapeutics, antibiotics and thiopurines are applied. The most effective are TNF-neutralizing antibodies, i.e. infliximab (IFX), adalimumab (ADA) and certolizumab (CER). Surgical management can be urgent including drainage. Elective procedures include dissection of the fistula (simple fistula) or more complex interventions such as mucosal flap or ligation of the intersphincteric portion of the fistula. Surgical interventions can be enhanced using the video-assisted anal fistula treatment (VAAFT) or negative-pressure therapy. In extreme cases, creation of a stoma may be necessary. Also, tissue glues or so-called plugs may be applied in managing perianal fistulas. The use of stem cells seems promising, i.e. application of multipotent non-hematopoietic stem cells around the fistula in order to induce immunomodulation and wound healing.
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Enfermedad de Crohn , Fístula Rectal , Terapia Combinada , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Drenaje , Humanos , Polonia , Fístula Rectal/etiología , Fístula Rectal/terapia , Resultado del TratamientoRESUMEN
BACKGROUND Boerhaave syndrome is a rare esophageal injury associated with a high mortality rate of 14.8%. Immediate diagnosis and treatment have been associated with a better outcome. Surgery remains the mainstay of treatment for those who present early with widespread septic contamination. One of the most difficult dilemmas in the treatment of Boerhaave syndrome is selection of the most appropriate management for late perforations with severe septic complications. In this situation, aggressive surgical approach with esophagectomy and immediate or postponed reconstruction is usually recommended. CASE REPORT We report a patient with spontaneous esophageal rupture successfully treated by late endoscopic stent-grafting. The patient was transferred from a rural hospital after initial non-effective conservative treatment. Endoscopic stent-grafting was performed 7 days from the onset of symptoms. A self-expanding plastic stent-graft (Polyflex) used initially very early migrated to the stomach. The plastic stent-graft was then replaced by a fully covered self-expandable metal stent-graft (EndoMAXX), which was wider and equipped with anti-migration struts. Implantation of the EndoMAXX stent-graft resulted in clinical success, with the closure of esophageal rupture confirmed 8 weeks after stent-grafting. CONCLUSIONS Our case indicates that even late after spontaneous esophageal perforation, less invasive treatment by endoscopic stent-grafting with adequate drainage of septic contamination may be an attractive option for preserving the esophagus in selected patients in stable hemodynamic condition. Our case also supports implantation of wider metallic stent-grafts to seal benign esophageal perforation above the esophago-gastric junction to prevent early migration to the stomach.
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Perforación del Esófago , Perforación del Esófago/etiología , Perforación del Esófago/cirugía , Esofagoscopía , Humanos , Enfermedades del Mediastino , Stents , Resultado del TratamientoRESUMEN
Mutations in IFN and MHC signaling genes endow immunotherapy resistance. Patients with colorectal cancer infrequently exhibit IFN and MHC signaling gene mutations and are generally resistant to immunotherapy. In exploring the integrity of IFN and MHC signaling in colorectal cancer, we found that optineurin was a shared node between the two pathways and predicted colorectal cancer patient outcome. Loss of optineurin occurs in early-stage human colorectal cancer. Immunologically, optineurin deficiency was shown to attenuate IFNGR1 and MHC-I expression, impair T-cell immunity, and diminish immunotherapy efficacy in murine cancer models and patients with cancer. Mechanistically, we observed that IFNGR1 was S-palmitoylated on Cys122, and AP3D1 bound with and sorted palmitoylated IFNGR1 to lysosome for degradation. Unexpectedly, optineurin interacted with AP3D1 to prevent palmitoylated IFNGR1 lysosomal sorting and degradation, thereby maintaining IFNγ and MHC-I signaling integrity. Furthermore, pharmacologically targeting IFNGR1 palmitoylation stabilized IFNGR1, augmented tumor immunity, and sensitized checkpoint therapy. Thus, loss of optineurin drives immune evasion and intrinsic immunotherapy resistance in colorectal cancer. SIGNIFICANCE: Loss of optineurin impairs the integrity of both IFNγ and MHC-I signaling pathways via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation, thereby driving immune evasion and intrinsic immunotherapy resistance in colorectal cancer. Our work suggests that pharmacologically targeting IFNGR1 palmitoylation can stabilize IFNGR1, enhance T-cell immunity, and sensitize checkpoint therapy in colorectal cancer.See related commentary by Salvagno and Cubillos-Ruiz, p. 1623.This article is highlighted in the In This Issue feature, p. 1601.
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Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorrectales/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Receptores de Interferón/metabolismo , Animales , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Femenino , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Interferón gamma/metabolismo , Lipoilación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Transporte de Proteínas , Organismos Libres de Patógenos Específicos , Receptor de Interferón gammaRESUMEN
BACKGROUND: The COVID-19 global pandemic left the unprepared health care systems struggling to mount a measured response. This gave rise to important questions about surgeons' attitude towards surgical practice and the level of preparation at work. METHODS: Cross-sectional web-based national survey distributed to general surgeons by email over a period of 7 days. RESULTS: Among 304 responders, 42.6% were working in the hospital with COVID-19 patients. Three quarters of all surgeons (74.5%) were afraid of contracting the disease. While 42% expressed a fear for their own life while caring for COVID-19 patients, 90.1% were afraid of transmitting the disease to family members. The average reported level of PPE provided at the workplace was significantly higher among the group which was not afraid of contracting COVID-19 than among the group afraid of contracting COVID-19 (4.0 vs. 3.12, pâ¯= 0.02). Nearly all surgeons (93.8%) agreed that cancer surgeries should be continued during the pandemic and 49% perceived laparoscopy as a safe approach when operating on COVID-19 positive patients. CONCLUSION: A high proportion of surgeons admitted being afraid of working during the COVID-19 pandemic, which had various implications for their attitude towards surgical practice. Protecting health care workers is an important component of public health measures for addressing the epidemic.
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BACKGROUND: Amplification of HER2 gene (ERBB2) and overexpression of HER2 protein on cancer cells are found in 10-26% of gastric cancer (GC) and esophagogastric junction cancer (EGJC). Gene copy number variation (CNV) could be detected in these patients in liquid biopsy and in cancer cells. METHODS: We analysed HER2 gene CNV used qPCR method in 87 sera collected from GC and EGJC patients before surgical treatment and in 40 sera obtained from healthy donors. HER2 gene CNV was also assessed in formalin-fixed paraffin-embedded (FFPE) tumor tissue. Furthermore, we assessed the number of HER2 gene copies and HER2 expression in cancer cells using the fluorescent in situ hybridization method (FISH) and immunohistochemistry (IHC). RESULTS: We found that the HER2 gene copy number in liquid biopsy was higher in GC and EGJC patients compared to healthy people (p = 0.01). Moreover, EGJC patients had higher number of HER2 gene copies than healthy donors (p = 0.0016). HER2 CNV examination could distinguish healthy individuals and patients with gastric or esophagogastric junction cancers with sensitivity and specificity of 58% and 98% (AUC = 0.707, 95% CI 0.593-0.821, p = 0.004). We found that patients with a high copy number of the HER2 gene in the tumor tissue assessed by qPCR (but not by FISH) have significantly more often a high number of HER2 gene copies in liquid biopsy (p = 0.04). CONCLUSIONS: We suggested that HER2 testing in liquid biopsy could be used as an auxiliary method to analysis of HER2 status in tumor tissue in gastric or esophagogastric junction cancers.