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1.
Inflamm Bowel Dis ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582044

RESUMO

Crohn's disease (CD) is a chronic inflammatory bowel disease with a multifactorial pathogenesis involving environmental and genetic factors. Since the late 20th century, the discovery of the first susceptibility gene (NOD2, previously referred to as CARD15) for CD has paved the way for further investigations into the correlations between clinical features and genetics, and its potential impact on clinical practice has fueled the research in the last 2 decades. Recent therapeutic advancements involving novel biologic drugs and small molecules have shifted inflammatory bowel disease management from a disease-centered to a patient-centric approach. To date, the role of NOD2 has not been fully understood yet. Recent data suggest that its clinical impact may be greater than currently recognized. This review overviews the most common NOD2 variants' role in real-life clinical practice. These genetic variants increase the risk of developing the disease and can aid in tailoring diagnosis and treatment. They are associated with the stricturing phenotype and ileal involvement and increase the risk of steroid refractoriness. In the meantime, limited and inconclusive evidence exists regarding their predictive role in response to azathioprine, biologic drugs, and small molecules. Eventually, their role in increasing the risk for surgery is evident, especially in those with the L1007fs variant. If further trials will support the initial evidence reported so far, NOD2 genetic variants will emerge as possible candidates for developing precision medicine in CD.


NOD2 is the most relevant susceptibility gene for Crohn's disease. It is associated with the tructuring disease phenotype, ileal involvement, and an increased risk for surgery. NOD2 genetic variants emerge as promising candidates for developing precision medicine in Crohn's disease.

3.
Front Oncol ; 13: 1132564, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36925919

RESUMO

Introduction: The Notch intracellular domain (NICD) and its ligands Jagged-1(Jag1), Delta-like ligand (DLL-3) and DLL4 play an important role in neoangiogenesis. Previous studies suggest a correlation between the tissue levels of NICD and response to therapy with bevacizumab in colorectal cancer (CRC). Another marker that may predict outcome in CRC is radiomics of liver metastases. The aim of this study was to investigate the expression of NICD and its ligands and the role of radiomics in the selection of treatment-naive metastatic CRC patients receiving bevacizumab. Methods: Immunohistochemistry (IHC) for NICD, Jag1 and E-cadherin was performed on the tissue microarrays (TMAs) of 111 patients with metastatic CRC treated with bevacizumab and chemotherapy. Both the intensity and the percentage of stained cells were evaluated. The absolute number of CD4+ and CD8+ lymphocytes was counted in three different high-power fields and the mean values obtained were used to determine the CD4/CD8 ratio. The positivity of tumor cells to DLL3 and DLL4 was studied. The microvascular density (MVD) was assessed in fifteen cases by counting the microvessels at 20x magnification and expressed as MVD score. Abdominal CT scans were retrieved and imported into a dedicated workstation for radiomic analysis. Manually drawn regions of interest (ROI) allowed the extraction of radiomic features (RFs) from the tumor. Results: A positive association was found between NICD and Jag1 expression (p < 0.001). Median PFS was significantly shorter in patients whose tumors expressed high NICD and Jag1 (6.43 months vs 11.53 months for negative cases; p = 0.001). Those with an MVD score ≥5 (CD31-high, NICD/Jag1 positive) experienced significantly poorer survival. The radiomic model developed to predict short and long-term survival and PFS yielded a ROC-AUC of 0.709; when integrated with clinical and histopathological data, the integrated model improved the predictive score (ROC-AUC of 0.823). Discussion: These results show that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy; the preliminary radiomic analyses show that the integration of quantitative information with clinical and histological data display the highest performance in predicting the outcome of CRC patients.

4.
Antibiotics (Basel) ; 11(10)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36289973

RESUMO

The burden of infections in acute care surgery (ACS) is huge. Surgical emergencies alone account for three million admissions per year in the United States (US) with estimated financial costs of USD 28 billion per year. Acute care facilities and ACS patients represent boost sanctuaries for the emergence, development and transmission of infections and multi-resistant organisms. According to the World Health Organization, healthcare-associated infections affected around 4 million cases in Europe and 1.7 million in the US alone in 2011 with 39,000 and 99,000 directly attributable deaths, respectively. In this scenario, antimicrobial resistance arose as a public-health emergency that worsens patients' morbidity and mortality and increases healthcare costs. The optimal patient care requires the application of comprehensive evidence-based policies and strategies aiming at minimizing the impact of healthcare associated infections and antimicrobial resistance, while optimizing the treatment of intra-abdominal infections. The present review provides a snapshot of two hot topics, such as antimicrobial resistance and systemic inflammatory response, and three milestones of infection management, such as source control, infection prevention, and control and antimicrobial stewardship.

5.
Front Surg ; 9: 991704, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061042

RESUMO

Purpose: Robotic surgery has been progressively implemented for colorectal procedures but is still limited for multiquadrant abdominal resections. The present study aims to describe our experience in robotic multiquadrant colorectal surgeries and provide a systematic review and meta-analysis of the literature investigating the outcomes of robotic total proctocolectomy (TPC), total colectomy (TC), subtotal colectomy (STC), or completion proctectomy (CP) compared to laparoscopy. Methods: At our institution 16 consecutive patients underwent a 2- or 3-stage totally robotic total proctocolectomy (TPC) with ileal pouch-anal anastomosis. A systematic review of the literature was performed to select studies on robotic and laparoscopic multiquadrant colorectal procedures. Meta-analyses were used to compare the two approaches. Results: In our case series, 14/16 patients underwent a 2-stage robotic TPC for ulcerative colitis with a mean operative time of 271.42 (SD:37.95) minutes. No conversion occurred. Two patients developed postoperative complications. The mean hospital stay was 8.28 (SD:1.47) days with no readmissions. Mortality was nil. All patients underwent loop-ileostomy closure, and functional outcomes were satisfactory. The literature appraisal was based on 23 retrospective studies, including 736 robotic and 9,904 laparoscopic multiquadrant surgeries. In the robotic group, 36 patients underwent STC, 371 TC, 166 TPC, and 163 CP. Pooled data analysis showed that robotic TC and STC had a lower conversion rate (OR = 0.17;95% CI, 0.04-0.82; p = 0.03) than laparoscopic TC and STC. The robotic approach was associated with longer operative time for TC and STC (MD = 104.64;95% CI, 18.42-190.87; p = 0.02) and TPC and CP (MD = 38.8;95% CI, 18.7-59.06; p = 0.0002), with no differences for postoperative complications and hospital stay. Reports on urological outcomes, sexual dysfunction, and quality of life were missing. Conclusions: Our experience and the literature suggest that robotic multiquadrant colorectal surgery is safe and effective, with low morbidity and mortality rates. Nevertheless, the overall level of evidence is low, and functional outcomes of robotic approach remain largely unknown. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022303016.

6.
Dig Liver Dis ; 54(5): 572-579, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35361566

RESUMO

BACKGROUND: Aim of the present report was to investigate the repercussions of COVID-19 pandemic on the procedural volumes and on the main indications of pediatric digestive endoscopy in Italy. METHODS: An online survey was distributed at the beginning of December 2020 to Italian digestive endoscopy centers. Data were collected comparing two selected time intervals: the first from 1st of February 2019 to 30th June 2019 and the second from 1st February 2020 to 30th June 2020. RESULTS: Responses to the survey came from 24 pediatric endoscopy Units. Globally, a reduction of 37.2% was observed between 2019 and 2020 periods with a significant decrease in median number of procedures (111 vs 57, p < 0.001). Both the median number of procedures performed for new diagnoses and those for follow-up purposes significantly decreased in 2020 (63 vs 36, p < 0.001 and 42 vs 21, p< 0.001, respectively). We reported a drastic reduction of procedures performed for suspected Celiac Disease and Functional Gastrointestinal Disorders (55.1% and 58.0%, respectively). Diagnostic endoscopies for suspected IBD decreased of 15.5%, whereas procedures for Mucosal Healing (MH) assessment reduced of 48.3%. CONCLUSIONS: Our study provides real-world data outlining the meaningful impact of COVID-19 on pediatric endoscopy practice in Italy.


Assuntos
COVID-19 , Criança , Endoscopia , Endoscopia Gastrointestinal , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Inquéritos e Questionários
7.
Int J Mol Sci ; 23(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35456940

RESUMO

Mutations in KRAS are among the most frequent aberrations in cancer, including colon cancer. KRAS direct targeting is daunting due to KRAS protein resistance to small molecule inhibition. Moreover, its elevated affinity to cellular guanosine triphosphate (GTP) has made the design of specific drugs challenging. Indeed, KRAS was considered 'undruggable'. KRASG12C is the most commonly mutated variant of KRAS in non-small cell lung cancer. Currently, the achievements obtained with covalent inhibitors of this variant have given the possibility to assess the best therapeutic approach to KRAS-driven tumors. Mutation-related biochemical assets and the tissue of origin are expected to influence responses to treatment. Further attempts to obtain mutant-specific KRAS (KRASG12C) switch-II covalent inhibitors are ongoing and the results are promising. Drugs targeted to block KRAS effector pathways could be combined with direct KRAS inhibitors, immunotherapy or T cell-targeting approaches in KRAS-mutant tumors. The development of valuable combination regimens will be essential against potential mechanisms of resistance that may arise during treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias do Colo , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética
8.
Microorganisms ; 9(12)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34946186

RESUMO

The relation between the gut microbiota and human health is increasingly recognized. Recently, some evidence suggested that dysbiosis of the oral microbiota may be involved in the development of digestive cancers. A systematic review was conducted according to the PRISMA guidelines to investigate the association between the oral microbiota and digestive cancers. Several databases including Medline, Scopus, and Embase were searched by three independent reviewers, without date restriction. Over a total of 1654 records initially identified, 28 studies (2 prospective cohort studies and 26 case-controls) were selected. They investigated oral microbiota composition in patients with esophageal squamous cell carcinoma (n = 5), gastric cancer (n = 5), colorectal cancer (n = 9), liver carcinoma (n = 2), and pancreatic cancer (n = 7). In most of the studies, oral microbiota composition was found to be different between digestive cancer patients and controls. Particularly, oral microbiota dysbiosis and specific bacteria, such as Fusobacterium nucleatum and Porphyromonas gingivalis, appeared to be associated with colorectal cancers. Current evidence suggests that differences exist in oral microbiota composition between patients with and without digestive cancers. Further studies are required to investigate and validate oral-gut microbial transmission patterns and their role in digestive cancer carcinogenesis.

9.
Int J Mol Sci ; 22(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34768901

RESUMO

Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed E⇔M states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI).


Assuntos
Carcinogênese , Diferenciação Celular , Transição Epitelial-Mesenquimal , Neoplasias Gastrointestinais/patologia , Células-Tronco Neoplásicas/patologia , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , Humanos , Células-Tronco Neoplásicas/metabolismo , Proteínas Nucleares/genética , Proteína 1 Relacionada a Twist/genética
10.
World J Emerg Surg ; 16(1): 35, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215310

RESUMO

BACKGROUND AND AIMS: Although rectal cancer is predominantly a disease of older patients, current guidelines do not incorporate optimal treatment recommendations for the elderly and address only partially the associated specific challenges encountered in this population. This results in a wide variation and disparity in delivering a standard of care to this subset of patients. As the burden of rectal cancer in the elderly population continues to increase, it is crucial to assess whether current recommendations on treatment strategies for the general population can be adopted for the older adults, with the same beneficial oncological and functional outcomes. This multidisciplinary experts' consensus aims to refine current rectal cancer-specific guidelines for the elderly population in order to help to maximize rectal cancer therapeutic strategies while minimizing adverse impacts on functional outcomes and quality of life for these patients. METHODS: The discussion among the steering group of clinical experts and methodologists from the societies' expert panel involved clinicians practicing in general surgery, colorectal surgery, surgical oncology, geriatric oncology, geriatrics, gastroenterologists, radiologists, oncologists, radiation oncologists, and endoscopists. Research topics and questions were formulated, revised, and unanimously approved by all experts in two subsequent modified Delphi rounds in December 2020-January 2021. The steering committee was divided into nine teams following the main research field of members. Each conducted their literature search and drafted statements and recommendations on their research question. Literature search has been updated up to 2020 and statements and recommendations have been developed according to the GRADE methodology. A modified Delphi methodology was implemented to reach agreement among the experts on all statements and recommendations. CONCLUSIONS: The 2021 SICG-SIFIPAC-SICE-WSES consensus for the multidisciplinary management of elderly patients with rectal cancer aims to provide updated evidence-based statements and recommendations on each of the following topics: epidemiology, pre-intervention strategies, diagnosis and staging, neoadjuvant chemoradiation, surgery, watch and wait strategy, adjuvant chemotherapy, synchronous liver metastases, and emergency presentation of rectal cancer.


Assuntos
Neoplasias Retais/terapia , Idoso , Gerenciamento Clínico , Humanos , Itália
11.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063506

RESUMO

The review begins with molecular genetics, which hit the field unveiling the involvement of oncogenes and tumor suppressor genes in the pathogenesis of colorectal cancer (CRC) and uncovering genetic predispositions. Then the notion of molecular phenotypes with different clinical behaviors was introduced and translated in the clinical arena, paving the way to next-generation sequencing that captured previously unrecognized heterogeneity. Among other molecular regulators of CRC progression, the extent of host immune response within the tumor micro-environment has a critical position. Translational sciences deeply investigated the field, accelerating the pace toward clinical transition, due to its strong association with outcomes. While the perturbation of gut homeostasis occurring in inflammatory bowel diseases can fuel carcinogenesis, micronutrients like vitamin D and calcium can act as brakes, and we discuss underlying molecular mechanisms. Among the components of gut microbiota, Fusobacterium nucleatum is over-represented in CRC, and may worsen patient outcome. However, any translational knowledge tracing the multifaceted evolution of CRC should be interpreted according to the prognostic and predictive frame of the TNM-staging system in a perspective of clinical actionability. Eventually, we examine challenges and promises of pharmacological interventions aimed to restrain disease progression at different disease stages.


Assuntos
Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Microambiente Tumoral/imunologia , Anticarcinógenos/farmacologia , Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos , Fusobacterium nucleatum/metabolismo , Microbioma Gastrointestinal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Micronutrientes/farmacologia , Microambiente Tumoral/genética , Microambiente Tumoral/fisiologia
12.
Clin Case Rep ; 9(4): 2485-2486, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33936724

RESUMO

The treatment of Bouveret syndrome lacks specific guidelines and is strictly interdisciplinary. Especially, if electrohydraulic lithotripsy is not available and endoscopic removal fails, a timely surgical approach is advised.

13.
World J Emerg Surg ; 16(1): 20, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926504

RESUMO

BACKGROUND: The effectiveness of surgical treatment for splenic flexure carcinomas (SFCs) in emergency settings remains unexplored. This study aims to compare the perioperative and long-term outcomes of different alternatives for emergency SFC resection. METHOD: This multicenter retrospective study was based on the SFC Study Group database. For the present analysis, SFC patients were selected if they had received emergency surgical resection with curative intent between 2000 and 2018. Extended right colectomy (ERC), left colectomy (LC), and segmental left colectomy (SLC) were evaluated and compared. RESULTS: The study sample was composed of 90 SFC patients who underwent emergency ERC (n = 55, 61.1%), LC (n = 18, 20%), or SLC (n = 17, 18.9%). Bowel obstruction was the most frequent indication for surgery (n = 75, 83.3%), and an open approach was chosen in 81.1% of the patients. A higher incidence of postoperative complications was observed in the ERC group (70.9%) than in the LC (44.4%) and SLC groups (47.1%), with a significant procedure-related difference for severe postoperative complications (Dindo-Clavien ≥ III; adjusted odds ratio for ERC vs. LC:7.23; 95% CI 1.51-34.66; p = 0.013). Anastomotic leakage occurred in 8 (11.2%) patients, with no differences between the groups (p = 0.902). R0 resection was achieved in 98.9% of the procedures, and ≥ 12 lymph nodes were retrieved in 92.2% of patients. Overall and disease-free survival rates at 5 years were similar between the groups and were significantly associated with stage pT4 and the presence of synchronous metastases. CONCLUSION: In the emergency setting, ERC and open surgery are the most frequently performed procedures. ERC is associated with increased odds of severe postoperative complications when compared to more conservative SFC resections. Nonetheless, all the alternatives seem to provide similar pathologic and long-term outcomes, supporting the oncological safety of more conservative resections for emergency SFCs.


Assuntos
Colectomia/métodos , Colo Transverso/cirurgia , Neoplasias do Colo/cirurgia , Emergências , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo Transverso/diagnóstico por imagem , Neoplasias do Colo/diagnóstico por imagem , Feminino , Humanos , Incidência , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
14.
Int J Mol Sci ; 21(24)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33353162

RESUMO

Understanding molecular features of colon cancer has shed light on its pathogenesis and progression. Over time, some of these features acquired clinical dignity and were incorporated in decision making. Namely, microsatellite instability (MSI) due to mismatch repair of defects, which primarily was adopted for the diagnosis of Lynch syndrome, became recognized as the biomarker of a different disease type, showing a less aggressive behavior. MSI tumors harbor high amounts of tumor infiltrating lymphocytes (TILs) due to their peculiar load in neoantigens. However, microsatellite stable colon cancer may also show high amounts of TILs, and this feature is as well associated with better outcomes. High TIL loads are in general associated with a favorable prognosis, especially in stage II colon cancer, and therein identifies a patient subset with the lowest probability of relapse. With respect to post-surgical adjuvant treatment, particularly in stage III, TILs predictive ability seems to weaken along with the progression of the disease, being less evident in high risk patients. Moving from cohort studies to the analysis of a series from clinical trials contributed to increase the robustness of TILs as a biomarker. The employment of high TIL densities as an indicator of good prognosis in early-stage colon cancers is strongly advisable, while in late-stage colon cancers the employment as an indicator of good responsiveness to post-surgical therapy requires refinement. It remains to be clarified whether TILs could help in identifying those patients with node-positive cancers to whom adjuvant treatment could be spared, at least in low-risk groups as defined by the TNM staging system.


Assuntos
Neoplasias do Colo/imunologia , Imunidade/imunologia , Linfócitos do Interstício Tumoral/imunologia , Instabilidade de Microssatélites , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Humanos
15.
Nutrients ; 12(11)2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233787

RESUMO

The reasons behind the increasing prevalence of celiac disease (CD) worldwide are still not fully understood. This study adopted a multilevel approach (in vitro, ex vivo, in vivo) to assess the potential of gluten from different wheat varieties in triggering CD. Peptides triggering CD were identified and quantified in mixtures generated from simulated gastrointestinal digestion of wheat varieties (n = 82). Multivariate statistics enabled the discrimination of varieties generating low impact on CD (e.g., Saragolla) and high impact (e.g., Cappelli). Enrolled subjects (n = 46) were: 19 healthy subjects included in the control group; 27 celiac patients enrolled for the in vivo phase. Celiacs were divided into a gluten-free diet group (CD-GFD), and a GFD with Saragolla-based pasta group (CD-Sar). The diet was followed for 3 months. Data were compared between CD-Sar and CD-GFD before and after the experimental diet, demonstrating a limited ability of Saragolla to trigger immunity, although not comparable to a GFD. Ex vivo studies showed that Saragolla and Cappelli activated immune responses, although with great variability among patients. The diverse potential of durum wheat varieties in triggering CD immune response was demonstrated. Saragolla is not indicated for celiacs, yet it has a limited potential to trigger adverse immune response.


Assuntos
Doença Celíaca/dietoterapia , Glutens/uso terapêutico , Triticum/química , Adolescente , Adulto , Idoso , Doença Celíaca/imunologia , Criança , Pré-Escolar , Dieta Livre de Glúten , Digestão , Feminino , Glutens/administração & dosagem , Humanos , Imunidade , Itália , Masculino , Pessoa de Meia-Idade , Peptídeos , Adulto Jovem
16.
Acta Biomed ; 91(3): e2020074, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32921770

RESUMO

Incidence of emergency access due to retained large rectal foreign bodies is increased in the last years. Such situations are a challenge because often, due to their size and physical characteristics, the large foreign bodies of the rectum cannot be extracted manually or by endoscopy, thus requiring surgery, as reported in the literature. We report a case of a 59-old male with a retention of a large vegetable rectal foreign body (whole eggplant) successfully subjected to endoscopic removal without the need for surgery.


Assuntos
Corpos Estranhos , Endoscopia , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Exame Físico , Reto/diagnóstico por imagem , Reto/cirurgia
17.
Sci Rep ; 10(1): 12238, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699266

RESUMO

Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30-40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1ß and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1ß, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes' cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.


Assuntos
Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Citocinas/metabolismo , Infliximab/uso terapêutico , Monócitos/metabolismo , Adulto , Idoso , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/fisiologia , Feminino , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Transcrição Gênica/fisiologia , Regulação para Cima/fisiologia , Adulto Jovem
18.
World J Emerg Surg ; 15(1): 32, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381121

RESUMO

Acute colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of acute left-sided colonic diverticulitis (ALCD) according to the most recent available literature. The update includes recent changes introduced in the management of ALCD. The new update has been further integrated with advances in acute right-sided colonic diverticulitis (ARCD) that is more common than ALCD in select regions of the world.


Assuntos
Doença Diverticular do Colo/classificação , Doença Diverticular do Colo/cirurgia , Serviço Hospitalar de Emergência , Doença Aguda , Humanos
19.
World J Emerg Surg ; 15(1): 27, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295644

RESUMO

BACKGROUND AND AIMS: Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy. METHODS: This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients. CONCLUSIONS: The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.


Assuntos
Dor Abdominal/diagnóstico , Dor Abdominal/cirurgia , Apendicite/diagnóstico , Apendicite/cirurgia , Guias de Prática Clínica como Assunto , Doença Aguda , Antibacterianos/uso terapêutico , Apendicectomia , Medicina Baseada em Evidências , Humanos , Laparoscopia/métodos
20.
World J Surg Oncol ; 17(1): 204, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791356

RESUMO

OBJECTIVES: Growing evidence supports the role of the intestinal microbiome in the carcinogenesis of colorectal cancers, but its impact on colorectal cancer surgery outcomes is not clearly defined. This systematic review aimed to analyze the association between intestinal microbiome composition and postoperative complication and survival following colorectal cancer surgery. METHODS: A systematic review was conducted according to the 2009 PRISMA guidelines. Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Human studies investigating the association between the intestinal microbiome and the short-term (anastomotic leakage, surgical site infection, postoperative ileus) and long-term outcomes (cancer-specific mortality, overall and disease-free survival) of colorectal cancer surgery were selected. Patients with any stage of colorectal cancer were included. The Newcastle-Ottawa scale for case-control and cohort studies was used for the quality assessment of the selected articles. RESULTS: Overall, 8 studies (7 cohort studies and 1 case-control) published between 2014 and 2018 were included. Only one study focused on short-term surgical outcomes, showing that anastomotic leakage is associated with low microbial diversity and abundance of Lachnospiraceae and Bacteroidaceae families in the non-cancerous resection lines of the stapled anastomoses of colorectal cancer patients. The other 7 studies focused on long-term oncological outcomes, including survival and cancer recurrence. The majority of the studies (5/8) found that a higher level of Fusobacterium nucleatum adherent to the tumor tissue is associated with worse oncological outcomes, in particular, increased cancer-specific mortality, decreased median and overall survival, disease-free and cancer-specific survival rates. Also a high abundance of Bacteroides fragilis was found to be linked to worse outcomes, whereas the relative abundance of the Prevotella-co-abundance group (CAG), the Bacteroides CAG, and the pathogen CAG as well as Faecalibacterium prausnitzii appeared to be associated with better survival. CONCLUSIONS: Based on the limited available evidence, microbiome composition may be associated with colorectal cancer surgery outcomes. Further studies are needed to elucidate the role of the intestinal microbiome as a prognostic factor in colorectal cancer surgery and its possible clinical implications.


Assuntos
Fístula Anastomótica/mortalidade , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/mortalidade , Cirurgia Colorretal/efeitos adversos , Microbioma Gastrointestinal , Complicações Pós-Operatórias , Fístula Anastomótica/etiologia , Neoplasias Colorretais/cirurgia , Humanos , Prognóstico , Taxa de Sobrevida
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