RESUMO
Abnormal epigenetic patterns correlate with effector T cell malfunction in tumours1-4, but the cause of this link is unknown. Here we show that tumour cells disrupt methionine metabolism in CD8+ T cells, thereby lowering intracellular levels of methionine and the methyl donor S-adenosylmethionine (SAM) and resulting in loss of dimethylation at lysine 79 of histone H3 (H3K79me2). Loss of H3K79me2 led to low expression of STAT5 and impaired T cell immunity. Mechanistically, tumour cells avidly consumed methionine and outcompeted T cells for methionine by expressing high levels of the methionine transporter SLC43A2. Genetic and biochemical inhibition of tumour SLC43A2 restored H3K79me2 in T cells, thereby boosting spontaneous and checkpoint-induced tumour immunity. Moreover, methionine supplementation improved the expression of H3K79me2 and STAT5 in T cells, and this was accompanied by increased T cell immunity in tumour-bearing mice and patients with colon cancer. Clinically, tumour SLC43A2 correlated negatively with T cell histone methylation and functional gene signatures. Our results identify a mechanistic connection between methionine metabolism, histone patterns, and T cell immunity in the tumour microenvironment. Thus, cancer methionine consumption is an immune evasion mechanism, and targeting cancer methionine signalling may provide an immunotherapeutic approach.
Assuntos
Sistema L de Transporte de Aminoácidos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Histonas/metabolismo , Metionina/metabolismo , Metilação , Neoplasias/metabolismo , Sistema L de Transporte de Aminoácidos/deficiência , Animais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Epigênese Genética , Feminino , Histonas/química , Humanos , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Receptores de Antígenos de Linfócitos T/metabolismo , Fator de Transcrição STAT5/metabolismoRESUMO
Little is known about how the immune system impacts human colorectal cancer invasiveness and stemness. Here we detected interleukin-22 (IL-22) in patient colorectal cancer tissues that was produced predominantly by CD4(+) T cells. In a mouse model, migration of these cells into the colon cancer microenvironment required the chemokine receptor CCR6 and its ligand CCL20. IL-22 acted on cancer cells to promote activation of the transcription factor STAT3 and expression of the histone 3 lysine 79 (H3K79) methytransferase DOT1L. The DOT1L complex induced the core stem cell genes NANOG, SOX2, and Pou5F1, resulting in increased cancer stemness and tumorigenic potential. Furthermore, high DOT1L expression and H3K79me2 in colorectal cancer tissues was a predictor of poor patient survival. Thus, IL-22(+) cells promote colon cancer stemness via regulation of stemness genes that negatively affects patient outcome. Efforts to target this network might be a strategy in treating colorectal cancer patients.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Neoplasias Colorretais/imunologia , Interleucinas/imunologia , Metiltransferases/imunologia , Células-Tronco Neoplásicas/imunologia , Fator de Transcrição STAT3/imunologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CCL20/imunologia , Quimiocina CCL20/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Ativação Enzimática/imunologia , Células HT29 , Histona-Lisina N-Metiltransferase , Proteínas de Homeodomínio/imunologia , Proteínas de Homeodomínio/metabolismo , Humanos , Metiltransferases/metabolismo , Camundongos , Proteína Homeobox Nanog , Transplante de Neoplasias , Células-Tronco Neoplásicas/patologia , Fator 3 de Transcrição de Octâmero/imunologia , Fator 3 de Transcrição de Octâmero/metabolismo , Receptores CCR6/imunologia , Receptores CCR6/metabolismo , Fatores de Transcrição SOXB1/imunologia , Fatores de Transcrição SOXB1/metabolismo , Fator de Transcrição STAT3/metabolismo , Interleucina 22RESUMO
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.
Assuntos
Neoplasias Colorretais , MicroRNAs , Radioterapia (Especialidade) , Humanos , MicroRNAs/genética , Carcinogênese , Neoplasias Colorretais/genéticaRESUMO
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.
Assuntos
Genes erbB-2 , Neoplasias Gástricas , Biomarcadores Tumorais , Variações do Número de Cópias de DNA , Junção Esofagogástrica , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Biópsia Líquida , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgiaRESUMO
B a c k g r o u n d: During COVID-19 pandemic, it is necessary to collect and analyze data concerning management of hospitals and wards to work out solutions for potential future crisis. The objective of the study was to investigate how surgical wards in Poland are managing during rapid development of the COVID-19 pandemic. M e t h o d s: An anonymous, online survey was designed and distributed to surgeons and surgery residents working in surgical departments during pandemic. Responders were divided into two groups: Group 1 (responders working in a "COVID-19-dedicated" hospital) and Group 2 (responders working in other hospitals). Results: Overall, 323 responders were included in the study group, 30.03% of which were female. Medical staff deficits were reported by 21.15% responders from Group 1 and 29.52% responders from Group 2 (p = 0.003). The mean number of elective surgeries performed weekly prior to the pandemic in Group 1 was 40.37 ± 46.31 and during the pandemic was 13.98 ± 37.49 (p < 0.001). In Group 2, the mean number of elective surgeries performed weekly before the start of the pandemic was 26.85 ± 23.52 and after the start of the pandemic, it was 7.65 ± 13.49 (p <0.001). There were significantly higher reported levels of preparedness in Group 1 in terms of: theoretical training of the staff, equipping the staff and adapting the operating theater to safely perform procedures on patients with COVID-19. Overall, 62.23% of responders presume being infected with SARS-CoV-2. C o n c l u s i o n s: SARS-CoV-2 pandemic had a significantly negative impact on surgical wards. Despite the preparations, the number of responders who presume being infected with SARS-CoV-2 during present crisis is high.
Assuntos
COVID-19/epidemiologia , Procedimentos Cirúrgicos Eletivos/tendências , Corpo Clínico Hospitalar/provisão & distribuição , Centro Cirúrgico Hospitalar , Feminino , Mão de Obra em Saúde , Hospitais Especializados , Humanos , Masculino , Polônia/epidemiologia , SARS-CoV-2 , Procedimentos Cirúrgicos Operatórios/tendências , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: OncoGel (Protherics Salt Lake City, Inc, Salt Lake City, UT) is paclitaxel (PTX) formulated in a thermosensitive, biodegradable copolymer for focused cytotoxicity and radiosensitization. A phase 2a study suggested that EUS-guided PTX injection into esophageal tumors subsequently receiving radiotherapy was safe. METHODS: In an international multicenter, prospective, randomized phase 2b study, patients with local or locoregional adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus/gastroesophageal junction and eligible for neoadjuvant chemoradiotherapy (CRT) before surgery were randomized to standard of care (SOC) plus EUS-guided PTX injection or SOC alone. PTX was injected in 0.5 to 1.0 mL aliquots throughout the tumor. Planned CRT as SOC was intravenous 5-fluorouracil for the first 4 days (weeks 1 and 5), intravenous cisplatin on the first day of each 5-fluorouracil course, and radiotherapy over 5.5 weeks. Patients were evaluated weekly during CRT and re-evaluated at 12 weeks for surgical eligibility and CT for change in overall tumor volume. RESULTS: The analysis included 137 patients (97 males; mean age, 58 ± 9.1 years) randomized to PTX + SOC (n = 72) and SOC (n = 65) by using a modified intention-to-treat approach. Overall response by tumor volume between the PTX (12.5%) and the SOC group (20.0%; P = .24; odds ratio, 0.57; 95% confidence interval, 0.23-1.44) was similar. Pathologic complete response was higher in the SOC group (26.2% vs 12.5%; P = .046); however, 12-month survival (P = .412) and the overall frequency of 1 or more adverse events (P = .17) were similar between the 2 groups. CONCLUSIONS: SOC + PTX is safe but does not improve overall survival or overall tumor response at the primary tumor site for patients with local or locoregional cancer of the esophagus/gastroesophageal junction. (Clinical trial registration number: NCT00573131.).
Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Adenocarcinoma/secundário , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/secundário , Quimiorradioterapia , Cisplatino/administração & dosagem , Endossonografia , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Fluoruracila/administração & dosagem , Humanos , Injeções Intralesionais , Análise de Intenção de Tratamento , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia , Critérios de Avaliação de Resposta em Tumores Sólidos , Taxa de Sobrevida , Carga TumoralRESUMO
BACKGROUND: Since the "War on Cancer" was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. DISCUSSION: Only a few types of cancer have been described that are associated with one major signaling pathway. This enabled the initial successful deployment of targeted therapy for such cancers. However, soon after this targeted approach was initiated, it was subverted as cancer cells learned and reacted to the initial treatments, oftentimes rendering the treatment less effective or even completely ineffective. During the past 30 plus years, the cancer classification used had, as its primary aim, the facilitation of communication and the exchange of information amongst those caring for cancer patients with the end goal of establishing a standardized approach for the diagnosis and treatment of cancers. This approach should be modified based on the recent research to affect a change from a service-based to an outcome-based approach. The vision of achieving long-term control and/or eradicating or curing cancer is far from being realized, but not impossible. In order to meet the challenges in getting there, any newly proposed anticancer strategy must integrate a personalized treatment outcome approach. This concept is predicated on tumor- and patient-associated variables, combined with an individualized response assessment strategy for therapy modification as suggested by the patient's own results. As combined strategies may be outcome-orientated and integrate tumor-, patient- as well as cancer-preventive variables, this approach is likely to result in an optimized anticancer strategy. SUMMARY: Herein, we introduce such an anticancer strategy for all cancer patients, experts, and organizations: Imagine a World without Cancer.
Assuntos
Detecção Precoce de Câncer , Neoplasias/diagnóstico , Neoplasias/terapia , Medicina de Precisão , Protocolos Antineoplásicos , Terapia Combinada , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/tendências , Humanos , Neoplasias/patologia , Medicina de Precisão/métodos , Medicina de Precisão/tendênciasRESUMO
BACKGROUND: The alimentary tract mucosa continuously releases mucus-rich secretion. Mucin, the major component of mucus, determines its viscosity and provides lubrication for the luminal content of indigestible food particles. AIMS: To measure mucin secretion rate and its viscosity in patients with chronic constipation (CC) and in asymptomatic volunteers. METHODS: Nineteen patients with symptoms of CC and 19 controls were included in the study. Mucin secretion and viscosity were assessed in aspirated gastric juice in basal conditions and after stimulation with pentagastrin (1 h each). Mucin content was tested by PAS methodology. Viscosity was measured using cone/plate digital viscometer. RESULTS: Mucin secretion rates in basal and stimulated conditions in controls were 65 and 42 % higher than in patients with CC (P < 0.05 and P < 0.001, respectively). Basal viscosity in controls was 48 % higher than in CC (P < 0.05) at the lowest and 55 % higher (P < 0.05) at the middle velocities. Viscosity in pentagastrin-stimulated conditions in controls was 71 % higher than in CC (P < 0.01) at the lowest and 35 % higher (P < 0.05) at the middle velocities. CONCLUSIONS: (1) The significantly lower rate of soluble mucin secretion in patients with CC than in normal volunteers may reflect impairment in mucin-related lubrication. (2) Significantly lower viscosity of gastric secretion in patients with CC may result from the lower rate of mucin secretion and may also diminish lubrication within the alimentary tract. (3) This may potentially set the stage for the development of symptoms related to chronic constipation and open a new therapeutic avenue for this patient population.
Assuntos
Constipação Intestinal/patologia , Mucinas Gástricas/química , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Mucinas Gástricas/fisiologia , Motilidade Gastrointestinal/fisiologia , Humanos , Pessoa de Meia-Idade , Viscosidade , Adulto JovemRESUMO
BACKGROUND: It has been previously demonstrated that the exposure of the lower esophageal mucosa to acid and pepsin results in significant increase in salivary protective factors secretion, mediated by the esophago-salivary reflex. The impact of the upper esophageal mucosal exposure to acid and pepsin on salivary secretory response remains unknown. AIMS: To investigate the rate of salivary protective factors secretion during the upper esophageal mucosal exposure to acid and pepsin and to compare with the corresponding results recorded during the lower esophageal mucosal exposure, in the same group of asymptomatic volunteers. METHODS: The study was conducted in 10 asymptomatic volunteers. Salivary samples were collected during the esophageal mucosal exposure to saline, followed by acid/pepsin and the final saline, using the esophageal perfusion catheter. Salivary bicarbonate and non-bicarbonate buffers were analyzed using TitraLab. Salivary mucin and protein were quantified through PAS and Lowry methodologies, respectively, whereas PE2 using radioimmunoassay. Statistical analysis was performed using Σ-Stat software. RESULTS: The rate of salivary bicarbonate secretion was significantly higher (3.1-fold) during the upper versus the lower esophageal mucosal exposure to acid and pepsin (87.5 ± 14.4 vs. 28.0 ± 7.70 µEq/min, p < 0.05). The volumes of saliva, pH, salivary protein, mucin and PE2 were similar in both esophageal perfusions. CONCLUSIONS: Threefold stronger secretion of salivary bicarbonate could be a major factor protecting the upper esophageal mucosa. This phenomenon may represent an ultimate defense mechanism potentially preventing further complications within the upper esophageal mucosa; however, it needs to be confirmed in patients of gastroesophageal reflux disease.
Assuntos
Bicarbonatos/química , Esôfago/patologia , Refluxo Gastroesofágico/patologia , Saliva/química , Adulto , Feminino , Ácido Gástrico , Humanos , Masculino , Pessoa de Meia-Idade , Pepsina ARESUMO
<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.
Assuntos
Estudantes de Medicina , Telemedicina , Humanos , Polônia , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários , Masculino , Feminino , Cirurgia Geral/educação , Competência Clínica , Educação de Graduação em Medicina/métodos , AdultoRESUMO
BACKGROUND: Laparoscopic cholecystectomy has become the treatment of choice for gallstone disease. Advantages of the laparoscopic approach include lower morbidity and mortality rates, reduced length of hospital stay, and earlier return to work. In acute cholecystitis, severe inflammation makes laparoscopic dissection technically more demanding, with a higher risk of related complications that require conversion to open cholecystectomy. METHODS: We reviewed the records of 5,596 patients who underwent cholecystectomy between 1993 and 2011 in a single institution. A laparoscopic approach was undertaken in 4,105 patients (73.4 %). The ultrasound signs of acute cholecystitis were found in 542 patients (13.2 %) who underwent laparoscopic cholecystectomy. We analyzed the ultrasound presentations of acute cholecystitis in patients who required conversion to open cholecystectomy and compared them with the ultrasound signs of acute cholecystitis in patients who had a completed laparoscopic cholecystectomy. RESULTS: A conversion to open cholecystectomy in patients with acute cholecystitis was necessary in 24 % (n = 130) of the patients compared to 3.4 % of the patients with uncomplicated gallstone disease. The most frequent ultrasound findings in patients requiring conversion were a pericholecystic exudate in 42 %, a difficult identification of anatomical structures due to local severe inflammation in 34 %, and gallbladder wall thickening of >5 mm in 31 %. Additionally, when the duration of symptoms exceeded 3 days, more than half of the patients required conversion to open cholecystectomy and the conversion rate was fivefold higher than for those with a shorter duration of acute cholecystitis. CONCLUSIONS: In patients with severe acute cholecystitis found on ultrasound, combined with gallbladder wall thickening to >5 mm, pericholecystic exudates or abscess adjacent to the gallbladder, difficulty identifying anatomical structures within Calot's triangle, specifically when the duration of symptoms exceeds 3 days, cholecystectomy should be done as an open approach because of the high risk of conversion.
Assuntos
Colecistectomia Laparoscópica , Colecistectomia , Colecistite Aguda/diagnóstico por imagem , Colecistite Aguda/cirurgia , Conversão para Cirurgia Aberta , Abscesso/diagnóstico por imagem , Bilirrubina/análise , Ducto Colédoco/diagnóstico por imagem , Exsudatos e Transudatos/diagnóstico por imagem , Vesícula Biliar/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Fatores de Tempo , UltrassonografiaRESUMO
BACKGROUND: Obesity has become a global epidemic and a leading metabolic disease in the world. Laparoscopic surgeries may influence the function of the immunologic system. The percentages of CD4+ and CD8+ T lymphocyte cells have been described as prognostic factors for patients undergoing abdominal surgeries. This study aimed to evaluate the changes in CD4+ and CD8+ T lymphocyte cells, the ratio of CD4+ to CD8+ cells, and the ZAP-70 kinase expression on T CD3+ and B CD19+ cells in obese and normal-weight individuals undergoing laparoscopic cholecystectomy (LC). METHODS: The study group consisted of 46 asymptomatic patients with gallstones shown by ultrasound examination but without signs of any gallbladder complications. The patients underwent planned LC. Blood samples were obtained at three times, and the percentages of studied cells were measured by flow cytometry. Patients were enrolled to two groups: N group (body mass index [BMI], ≤ 25 kg/m(2)) and O group (BMI, ≥ 30 kg/m(2)). For statistical analysis, the Mann-Whitney U test and the Wilcoxon matched-pairs signed-ranks test were used. All p values lower than 0.05 were considered significant. RESULTS: The percentage of CD4+ T cells did not differ between the N and O groups before or after the surgery. Only in the N group did the percentage of CD4+ lymphocytes increase from 0 to 48 h. A higher percentage of CD8+ lymphocytes was observed in the O group postoperatively than in the N group. Differences of ZAP-70 kinase expression in the O group were observed at 24 and 48 h of the study. Decreased expression of ZAP-70 kinase was shown in the N group at both 0-24 and 24-48 h. In the O group, this tendency was noted at 24-48 h. CONCLUSIONS: Immunologic activation after LC was confirmed in both weight groups. However, higher modulation, more typical for open surgeries, was observed in the obese group.
Assuntos
Colecistectomia Laparoscópica , Cálculos Biliares/cirurgia , Obesidade/imunologia , Linfócitos T/imunologia , Proteína-Tirosina Quinase ZAP-70/metabolismo , Adulto , Idoso , Antígenos CD19/metabolismo , Complexo CD3/metabolismo , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Cálculos Biliares/enzimologia , Cálculos Biliares/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/enzimologia , Adulto JovemRESUMO
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.
Assuntos
Complicações Pós-Operatórias , Qualidade de Vida , Humanos , Resultado do Tratamento , Fatores de Risco , Período Perioperatório , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
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.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Antígeno Carcinoembrionário/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologiaRESUMO
<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.
Assuntos
Adenocarcinoma , Apolipoproteína A-I , Apolipoproteínas B , Biomarcadores , Neoplasias Gástricas , Humanos , Adenocarcinoma/tratamento farmacológico , Apolipoproteína A-I/análise , Apolipoproteínas B/análise , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológicoRESUMO
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.
RESUMO
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.
Assuntos
Nomogramas , Neoplasias Gástricas , Humanos , Prognóstico , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Linfonodos/patologiaRESUMO
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.
Assuntos
Procedimentos Cirúrgicos Eletivos , Assistência Perioperatória , Humanos , Consenso , Assistência Perioperatória/métodos , Complicações Pós-Operatórias , Tempo de InternaçãoRESUMO
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.
RESUMO
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.