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1.
Anticancer Res ; 41(10): 5147-5155, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593466

RESUMO

BACKGROUND/AIM: Metastatic small bowel adenocarcinoma (SBA) is a rare disease with poor prognosis. This study aimed to explore the efficacy and safety of second-line chemotherapy for patients with SBA. PATIENTS AND METHODS: We retrospectively reviewed the clinical characteristics of 27 metastatic patients with SBA after progression on first-line chemotherapy. The patients were divided into Cohort A, receiving second-line chemotherapy, and Cohort B, receiving best supportive care. RESULTS: Patients in Cohort B had higher age, worse performance status, and higher neutrophil-to-lymphocyte ratio compared with those in Cohort A. Cohort A showed significantly better overall survival (OS) compared with Cohort B (median OS, 15.6 vs. 3.4 months; p=0.002). Objective response rate, disease control rate, and median progression-free survival (PFS) for Cohort A were 7%, 74%, and 5.0 months, respectively. Patients who underwent irinotecan-based chemotherapy showed longer PFS and OS compared with those who underwent taxane-based chemotherapy. No significant adverse events were reported. CONCLUSION: Second-line chemotherapy for metastatic SBA demonstrated clinical activity with acceptable toxicities.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Intestinais/mortalidade , Intestino Delgado/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/patologia , Intestino Delgado/efeitos dos fármacos , Irinotecano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem
2.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638785

RESUMO

For a yet unknown reason, a substantial share of patients suffering from COVID-19 develop long-lasting neuropsychiatric symptoms ranging from cognitive deficits to mood disorders and/or an extreme fatigue. We previously reported that in non-neural cells, angiotensin-1 converting enzyme 2 (ACE2), the gene coding for the SARS-CoV2 host receptor, harbors tight co-expression links with dopa-decarboxylase (DDC), an enzyme involved in the metabolism of dopamine. Here, we mined and integrated data from distinct human expression atlases and found that, among a wide range of tissues and cells, enterocytes of the small intestine express the highest expression levels of ACE2, DDC and several key genes supporting the metabolism of neurotransmitters. Based on these results, we performed co-expression analyses on a recently published set of RNA-seq data obtained from SARS-CoV2-infected human intestinal organoids. We observed that in SARS-CoV2-infected enterocytes, ACE2 co-regulates not only with DDC but also with a specific group of genes involved in (i) the dopamine/trace amines metabolic pathway, (ii) the absorption of microbiota-derived L-DOPA and (iii) the absorption of neutral amino acids serving as precursors to neurotransmitters. We conclude that in patients with long COVID, a chronic infection and inflammation of small intestine enterocytes might be indirectly responsible for prolonged brain alterations.


Assuntos
Encéfalo/patologia , COVID-19/complicações , Regulação da Expressão Gênica , Intestino Delgado/patologia , Enzima de Conversão de Angiotensina 2/genética , Descarboxilases de Aminoácido-L-Aromático/genética , Encéfalo/metabolismo , COVID-19/genética , COVID-19/patologia , Células Cultivadas , Enterócitos/metabolismo , Enterócitos/patologia , Humanos , Intestino Delgado/metabolismo , SARS-CoV-2/isolamento & purificação
3.
Int J Mol Sci ; 22(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34298894

RESUMO

(1) The high-fat diet (HFD) of western countries has dramatic effect on the health of several organs, including the digestive tract, leading to the accumulation of fats that can also trigger a chronic inflammatory process, such as that which occurs in non-alcohol steatohepatitis. The effects of a HFD on the small intestine, the organ involved in the absorption of this class of nutrients, are still poorly investigated. (2) To address this aspect, we administered a combined HFD with sucrose (HFD w/Suc, fat: 58% Kcal) regimen (18 months) to mice and investigated the morphological and molecular changes that occurred in the wall of proximal tract of the small intestine compared to the intestine of mice fed with a standard diet (SD) (fat: 18% Kcal). (3) We found an accumulation of lipid droplets in the mucosa of HFD w/Suc-fed mice that led to a disarrangement of mucosa architecture. Furthermore, we assessed the expression of several key players involved in lipid metabolism and inflammation, such as perilipin, leptin, leptin receptor, PI3K, p-mTOR, p-Akt, and TNF-α. All these molecules were increased in HFD mice compared to the SD group. We also evaluated anti-inflammatory molecules like adiponectin, adiponectin receptor, and PPAR-γ, and observed their significant reduction in the HFD w/Suc group compared to the control. Our data are in line with the knowledge that improper eating habits present a primary harmful assault on the bowel and the entire body's health. (4) These results represent a promising starting point for future studies, helping to better understand the complex and not fully elucidated spectrum of intestinal alterations induced by the overconsumption of fat.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/administração & dosagem , Sacarose na Dieta/efeitos adversos , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Adiponectina/metabolismo , Animais , Comportamento Alimentar/fisiologia , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Receptores para Leptina/metabolismo
4.
JSLS ; 25(2)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248336

RESUMO

Background: We sought to assess hernia characteristics and classification through comprehensive review of the literature involving broad ligament herniation. Methods: A literature search via MEDLINE and Embase databases was conducted to identify and select broad ligament herniation studies published between January 1, 2000 and September 30, 2020. Extracted data included previous surgical history, previous obstetric history, diagnostic imaging, herniated organ, hernia classification, and repair performed. The reported data has been compared to a unique case of broad ligament herniation that presented to our institution. Results: A total of 44 articles with 49 cases were identified for the study. Eighteen (36.7%) patients had a history of previous abdominal surgery while 29 (59.2%) had a history of previous childbirth. Type I (51.0%) and Type II (18.4%) defects were most commonly reported with most patients reporting only one defect (85.7%) using the Cilley classification. Twenty-nine patients underwent primary laparoscopic repair of the defect while 19 patients underwent exploratory laparotomy. Conclusions: The analysis of previously reported cases adds to the limited literature on broad ligament hernias and highlights the surgical management of this uncommon pathology. It also highlights the need for a broad differential diagnosis when female patients present with pelvic pain or symptoms of small bowel obstruction. The broad ligament should be fully inspected when mesenteric defects are suspected as multiple defects can be present as evidenced by the attached case study.


Assuntos
Ligamento Largo/patologia , Hérnia/diagnóstico , Dor Pélvica/diagnóstico , Adulto , Ligamento Largo/cirurgia , Diagnóstico Diferencial , Feminino , Hérnia/patologia , Herniorrafia/métodos , Humanos , Obstrução Intestinal/diagnóstico , Intestino Delgado/patologia , Laparoscopia/métodos , Laparotomia/métodos , Pessoa de Meia-Idade , Dor Pélvica/patologia
5.
Ann Palliat Med ; 10(7): 7440-7457, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34263641

RESUMO

BACKGROUND: Small intestine cancers, as an extremely rare tumor type, account only for 3% of all gastrointestinal tumors. Small intestine adenocarcinoma (SIA), representing approximately one-third of all small bowel cancers, has received relatively little attention, both in research efforts and clinical cognizance. Owing to anatomical proximity and rarity, small bowel adenocarcinomas are frequently grouped with colorectal adenocarcinomas. Therefore, a large SIA patient cohort is needed to develop and validate new nomogram prognostic models specific to SIA patients. METHODS: Patients diagnosed with SIA between 2004 and 2016 were extracted from the Surveillance, Epidemiology, and Final Results (SEER) database. All patients were randomly assigned to the training cohort and the validation cohort (2:1). The basic clinical information, detailed pathological staging, and treatment information of the patients were included in the analysis. Nomograms were shaped following the evaluations of the Cox regression model and verified using the decision curve analysis (DCA), time-dependent receiver operating characteristic (ROC) curves, concordance index (C-index), and calibration curves. RESULTS: The entire group comprised 6,947 patients with small intestine adenocarcinoma. According to the results of the multivariate Cox regression analysis, ten variables, including marital status, age, pathological grade, tumor location, T (tumor), N (nodes), M (metastasis) stage, surgery, chemotherapy, and regional nodes examined (RNE), were independent predictors of both of overall survival (OS) and cancer-specific survival (CSS). All significant variables were used to create the nomograms for OS and CSS. Various methods verified the reliability of the nomograms. The C-indexes of the OS and CSS nomogram were 0.756 (95% CI, 0.748-0.764) and 0.771 (95% CI, 0.761-0.781) in the training cohort and 0.748 (95% CI, 0.736-0.760) and 0.767 (95% CI, 0.752-0.781) in the validation cohort. The calibration curve showed good agreement between the nomogram prediction and actual survival. DCA indicated a clear net benefit of these new forecasting models. CONCLUSIONS: This study built and verified nomograms to predict OS and CSS for rare SIA, which appear to be excellent tools to augment the clinically available evidence to facilitate the discussion between SIA patients and clinicians regarding therapeutic choice.


Assuntos
Adenocarcinoma , Nomogramas , Adenocarcinoma/patologia , Humanos , Intestino Delgado/patologia , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Programa de SEER
6.
AAPS PharmSciTech ; 22(5): 200, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212283

RESUMO

Mucositis is one of the most adverse effects of 5-fluorouracil (5-FU) and had no standard drug for treatment. Melatonin is a neurohormone, and can ameliorate radiotherapy-induced small intestinal mucositis. Melatonin encapsulated in niosomes improved its poor bioavailability. Succinyl melatonin, a melatonin derivative, showed prolonged release compared with melatonin. This study investigated the efficacy of melatonin niosome gel (MNG) and succinyl melatonin niosome gel (SNG) in 5-FU-induced small intestinal mucositis treatment in mice. MNG and SNG with particle sizes of 293 and 270 nm were shown to have mucoadhesive potentials. The effect of a daily oral application of MNG, SNG, or fluocinolone acetonide gel (FAG, positive control) was compared to that of the normal group. The body weight, food consumption, histology, Fourier transform infrared (FTIR) spectroscopy, inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß), and malondialdehyde (MDA) in the small intestine were monitored. The results showed decreased %body weight and food consumption in all 5-FU-injected groups compared with the normal group. The MNG and SNG treatments maintained the food consumption and the normal integrity of the small intestines, as evidenced by villus length and crypt depth, similar to the observations in the normal groups. The FTIR spectra showed no change in lipids of the MNG and SNG groups compared with the normal group. Moreover, SNG could reduce IL-1ß content to a level that was not different from the level in the normal groups. Therefore, the oral application of MNG and SNG could protect against 5-FU-induced small intestinal mucositis in mice.


Assuntos
Lipossomos/química , Melatonina/administração & dosagem , Mucosite/tratamento farmacológico , Administração Oral , Animais , Fluoruracila/toxicidade , Interleucina-1beta/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestino Delgado/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Melatonina/química , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Mucosite/induzido quimicamente , Mucosite/patologia , Tamanho da Partícula , Fator de Necrose Tumoral alfa/metabolismo
7.
Int J Mol Sci ; 22(14)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34299046

RESUMO

The small intestine has a high rate of cell turnover under homeostatic conditions, and this increases further in response to infection or damage. Epithelial cells mostly die by apoptosis, but recent studies indicate that this may also involve pro-inflammatory pathways of programmed cell death, such as pyroptosis and necroptosis. Celiac disease (CD), the most prevalent immune-based enteropathy, is caused by loss of oral tolerance to peptides derived from wheat, rye, and barley in genetically predisposed individuals. Although cytotoxic cells and gluten-specific CD4+ Th1 cells are the central players in the pathology, inflammatory pathways induced by cell death may participate in driving and sustaining the disease through the release of alarmins. In this review, we summarize the recent literature addressing the role of programmed cell death pathways in the small intestine, describing how these mechanisms may contribute to CD and discussing their potential implications.


Assuntos
Apoptose , Doença Celíaca/patologia , Intestino Delgado/patologia , Animais , Doença Celíaca/etiologia , Humanos
8.
Am J Gastroenterol ; 116(7): 1506-1513, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34183578

RESUMO

INTRODUCTION: To identify factors associated with irreversible transmural necrosis (ITN) among critically ill patients experiencing nonocclusive mesenteric ischemia (NOMI) and to compare the predictive value regarding ITN risk stratification with that of the previously described Clichy score. METHODS: All consecutive patients admitted to the intensive care unit between 2009 and 2019 who underwent exploratory laparotomy for NOMI and who had an available contrast-enhanced computed tomography with at least 1 portal venous phase were evaluated for inclusion. Clinical, laboratory, and radiological variables were collected. ITN was assessed on pathological reports of surgical specimens and/or on laparotomy findings in cases of open-close surgery. Factors associated with ITN were identified by univariate and multivariate analysis to derive a NOMI-ITN score. This score was further compared with the Clichy score. RESULTS: We identified 4 factors associated with ITN in the context of NOMI: absence of bowel enhancement, bowel thinning, plasma bicarbonate concentration ≤15 mmol/L, and prothrombin rate <40%. These factors were included in a new NOMI-ITN score, with 1 point attributed for each variable. ITN was observed in 6%, 38%, 65%, 88%, and 100% of patients with NOMI-ITN score ranging from 0 to 4, respectively. The NOMI-ITN score outperformed the Clichy score for the prediction of ITN (area under the receiver operating characteristics curve 0.882 [95% confidence interval 0.826-0.938] vs 0.674 [95% confidence interval 0.582-0.766], respectively, P < 0.001). DISCUSSION: We propose a new 4-point score aimed at stratifying risk of ITN in patients with NOMI. The Clichy score should be applied to patients with occlusive acute mesenteric ischemia only.


Assuntos
Intestino Delgado/patologia , Isquemia Mesentérica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bicarbonatos/sangue , Estado Terminal , Feminino , Humanos , Intestino Delgado/irrigação sanguínea , Intestino Delgado/diagnóstico por imagem , Laparotomia , Masculino , Isquemia Mesentérica/sangue , Isquemia Mesentérica/complicações , Isquemia Mesentérica/diagnóstico por imagem , Pessoa de Meia-Idade , Análise Multivariada , Necrose , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Modelos de Riscos Proporcionais , Tempo de Protrombina , Medição de Risco , Sepse/complicações , Tomografia Computadorizada por Raios X
9.
Artigo em Inglês | MEDLINE | ID: mdl-34172256

RESUMO

Several machine learning algorithms have been developed in the past years with the aim to improve SBCE (Small Bowel Capsule Endoscopy) feasibility ensuring at the same time a high diagnostic accuracy. If past algorithms were affected by low performances and unsatisfactory accuracy, deep learning systems raised up the expectancy of effective AI (Artificial Intelligence) application in SBCE reading. Automatic detection and characterization of lesions, such as angioectasias, erosions and ulcers, would significantly shorten reading time other than improve reader attention during SBCE review in routine activity. It is debated whether AI can be used as first or second reader. This issue should be further investigated measuring accuracy and cost-effectiveness of AI systems. Currently, AI has been mostly evaluated as first reader. However, second reading may play an important role in SBCE training as well as for better characterizing lesions for which the first reader was uncertain.


Assuntos
Inteligência Artificial/normas , Endoscopia por Cápsula/métodos , Aprendizado Profundo/normas , Intestino Delgado/patologia , Aprendizado de Máquina/normas , Humanos
11.
Environ Toxicol Pharmacol ; 86: 103672, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33989784

RESUMO

Clinical studies have shown that Intrahepatic cholestasis is closely related to intestinal injury. The gut-liver axis theory suggests that the intestine and liver are closely related, and that bile acids are important mediators linking the intestine and liver. We compared two cholestasis models: a single injection model that received a single subcutaneous ANIT injection (75 mg/kg), and a multiple subcutaneous injection model that received an injection of ANIT (50 mg/kg) every other day for 2 weeks. We used Transmetil (ademetionine 1,4-butanedisulfonate) to relieve intrahepatic cholestasis in the multiple injection group. In the multiple injection group, we found increased hepatic bile duct hyperplasia, increased fibrosis of the liver, increased small intestine inflammation and oxidative damage, increased harmful bile acids, decreased bile acids transporter levels. After treatment with Transmetil, the liver and gut injuries were relieved. These results suggest that intrahepatic cholestasis can cause disorders of the gut-liver axis.


Assuntos
1-Naftilisotiocianato , Colestase Intra-Hepática/induzido quimicamente , Enteropatias/induzido quimicamente , Cirrose Hepática/induzido quimicamente , Animais , Ácidos e Sais Biliares/análise , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/patologia , Citocinas/genética , Fezes/química , Enteropatias/genética , Enteropatias/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL
12.
J Cell Mol Med ; 25(12): 5470-5485, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33963805

RESUMO

As the potential risk of radiation exposure is increasing, radioprotectors studies are gaining importance. In this study, novel hybrid compounds containing edaravone analogue and 3-n-butylphthalide ring-opening derivatives were synthesized, and their radioprotective effects were evaluated. Among these, compound 10a displayed the highest radioprotective activity in IEC-6 and HFL-1 cells. Its oral administration increased the survival rates of irradiated mice and alleviated total body irradiation (TBI)-induced hematopoietic damage by mitigating myelosuppression and improving hematopoietic stem/progenitor cell frequencies. Furthermore, 10a treatment prevented abdominal irradiation (ABI)-induced structural damage to the small intestine. Experiment results demonstrated that 10a increased the number of Lgr5+ intestinal stem cells, lysozyme+ Paneth cells and Ki67+ transient amplifying cells, and reduced apoptosis of the intestinal epithelium cells in irradiated mice. Moreover, in vitro and in vivo studies demonstrated that the radioprotective activity of 10a is associated to the reduction of oxidative stress and the inhibition of DNA damage. Furthermore, compound 10a downregulated the expressions of p53, Bax, caspase-9 and caspase-3, and upregulated the expression of Bcl-2, suggesting that it could prevent irradiation-induced intestinal damage through the p53-dependent apoptotic pathway. Collectively, these findings demonstrate that 10a is beneficial for the prevention of radiation damage and has the potential to be a radioprotector.


Assuntos
Benzofuranos/farmacologia , Edaravone/farmacologia , Células Epiteliais/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Protetores contra Radiação/farmacologia , Animais , Apoptose , Dano ao DNA , Edaravone/sangue , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/efeitos da radiação , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Intestino Delgado/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Protetores contra Radiação/química , Irradiação Corporal Total/efeitos adversos
13.
Khirurgiia (Mosk) ; (6): 45-53, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34029035

RESUMO

OBJECTIVE: To improve the outcomes of therapy of acute adhesive small bowel obstruction via development of a comprehensive management including CT, deep endoscopy-assisted nasointestinal drainage of small bowel with injection of a water-soluble contrast. MATERIAL AND METHODS: There were 128 patients with acute adhesive small bowel obstruction for the period from 2015 to 2018. The study included 2 groups of patients depending on therapeutic approach and duration of treatment. In the first group, conventional approach for acute adhesive small bowel obstruction was applied. Upon admission, all patients with confirmed acute adhesive small bowel obstruction underwent gastric intubation for decompression of the upper gastrointestinal tract. Barium sulfate injection followed by X-ray examination was performed to assess an effectiveness of therapy. In the second group, computed tomography was performed in addition to X-ray examination and ultrasound. Moreover, conservative treatment included deep endoscopy-assisted nasointestinal drainage and subsequent administration of a water-soluble contrast in addition to traditional approaches. RESULTS: Therapy was effective in 99 (71.2%) patients; 39 (28.8%) ones required surgery. Deep endoscopy-assisted nasointestinal drainage with injection of a water-soluble contrast was effective in 45 (78.9%) patients. Overall mortality in traditional approach was 1.4%, postoperative mortality - 3.7%. There were no lethal outcomes in case of a new approach. CONCLUSION: Deep endoscopy-assisted nasointestinal drainage with injection of a water-soluble contrast is the most effective therapeutic method for acute adhesive small bowel obstruction (78.9%). These findings can significantly improve treatment outcomes in these patients.


Assuntos
Tratamento Conservador , Obstrução Intestinal , Adesivos , Meios de Contraste , Diatrizoato de Meglumina , Humanos , Obstrução Intestinal/patologia , Obstrução Intestinal/terapia , Intestino Delgado/patologia , Aderências Teciduais/complicações , Aderências Teciduais/patologia , Aderências Teciduais/terapia
14.
Pan Afr Med J ; 38: 213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046119

RESUMO

The small bowel is the least common site for diverticula in the entire gastrointestinal tract. Chronic upper intestinal obstruction due to diverticula is very rare. We report a case of multiple small bowel diverticula causing mechanical obstruction of the duodenojejunal flexure.


Assuntos
Doenças Diverticulares/complicações , Obstrução Duodenal/diagnóstico , Doenças do Jejuno/diagnóstico , Obstrução Duodenal/etiologia , Feminino , Humanos , Intestino Delgado/patologia , Doenças do Jejuno/etiologia , Pessoa de Meia-Idade
15.
Curr Opin Oncol ; 33(4): 368-371, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33882527

RESUMO

PURPOSE OF REVIEW: Small bowel adenocarcinoma (SBA) is a rare disease, for which few studies have been conducted so far. Therefore, most treatment recommendations have been extrapolated from trials in colorectal cancer. In this review, we revise available data that could improve the management of SBA, with a particular focus on systemic therapy. RECENT FINDINGS: For advanced/irresectable disease, first-line doublet chemotherapy remains standard of care. It is uncertain whether extending treatment to triplet chemotherapy brings added benefit. Pembrolizumab is an accepted treatment modality for mismatch repair-deficient tumors, yet might also be active in microsatellite stable tumors. More trials with immunotherapy are underway. Although there is no place for anti-EGFR monotherapy, the addition of cetuximab to chemotherapy should be investigated further. Two trials suggest an added value of bevacizumab to chemotherapy, yet larger trials are needed to confirm these data. For localized disease, the role of (neo)adjuvant chemotherapy is under investigation. SUMMARY: For decades, patients with SBA have probably been treated suboptimal by basing treatment recommendations on data from colorectal cancer. An effort for SBA-specific trials and/or inclusion of SBA patients in basket trials is of utmost importance in order to improve outcome for these patients.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Intestino Delgado/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Antineoplásicos Imunológicos/administração & dosagem , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Humanos , Neoplasias Intestinais/imunologia , Neoplasias Intestinais/patologia , Intestino Delgado/imunologia , Inibidores de Proteínas Quinases/administração & dosagem , Doenças Raras/tratamento farmacológico
16.
Front Immunol ; 12: 625627, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790896

RESUMO

Melatonin reportedly alleviates sepsis-induced multi-organ injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1-7). However, whether melatonin attenuates small-intestine injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of mice and ameliorated multiple-organ injury (lung/liver/kidney/small intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1. We confirmed this mechanistic effect in a CLP-induced sepsis model of intestinal SIRT3 conditional-knockout mice, and found that melatonin preserved mitochondrial function and induced autophagy of small-intestine epithelial cells; these effects were dependent on SIRT3 activation. This study has shown, to the best of our knowledge, for the first time that melatonin alleviates sepsis-induced small-intestine injury, at least partially, by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial-function protection, and autophagy induction.


Assuntos
Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Melatonina/farmacologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sepse/tratamento farmacológico , Sirtuína 3/metabolismo , Animais , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/enzimologia , Mucosa Intestinal/patologia , Intestino Delgado/enzimologia , Intestino Delgado/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Sepse/enzimologia , Sepse/microbiologia , Sepse/patologia , Sirtuína 1/metabolismo , Sirtuína 3/genética
17.
Dig Dis Sci ; 66(7): 2173-2176, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33835376

RESUMO

INTRODUCTION: Small bowel involvement is very common in Crohn's disease. Ileocolonoscopy, cross-sectional imaging modalities, and video capsule endoscopy are the tools currently used to investigate such involvement. AREAS COVERED: Herein we report the case of a 47-year-old man with a history of ileocolic Crohn's disease and persistent, unexplained iron deficiency anemia. EXPERT COMMENTARY: Capsule endoscopy, by accurately identifying small intestinal mucosal lesions, can improve outcomes.


Assuntos
Endoscopia por Cápsula/métodos , Doença de Crohn/patologia , Intestino Delgado/patologia , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Trauma Acute Care Surg ; 90(6): 917-923, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33797496

RESUMO

BACKGROUND: Preoperative identification of the cause of adhesive small bowel obstruction (ASBO) is crucial for decision making. Some computed tomography (CT) findings can be indicative of single adhesive bands or matted adhesions. Our aim was to build a predictive model based on CT data to discriminate ASBO due to single adhesive band or matted adhesions. METHODS: A retrospective single center study was conducted, covering all consecutive patients with a preoperative CT scan, undergoing urgent surgery for ASBO between January 1, 2005, and December 31, 2017. Preoperative CT scans were blindly reviewed, and all the CT findings indicative of single adhesive band or matted adhesions described in literature were recorded. According to intraoperative findings, ASBOs were retrospectively classified into single band and matted ASBO. All observed CT findings were compared between the two groups. A predictive model based on logistic regression was developed, and its ability was quantified by discrimination and calibration. Internal cross-validation was conducted by bootstrap resampling. RESULTS: A total of 116 patients were analyzed (males, 53.5%; median age, 68 years; single band ASBO in 65.5% of cases). The odds of single band ASBO were increased four times in presence of complete obstruction (odds ratios, 4.19; 95% confidence interval, 1.49-12.56) and seven times in presence of fat notch sign (odds ratios, 7.37; 95% confidence interval, 1.83-40.03). The predictive model combining all CT findings had an accuracy of 86% in single band ASBO prediction. Accuracy decreased to 79% in the internal validation. Sensitivity, specificity, and positive and negative predictive values were calculated at different cut-points of the predicted risk: using a 0.70 cut-point, the specificity is 80%, the sensitivity is 68%, and the positive and negative predictive values are 87% and 57%, respectively. CONCLUSION: The proposed predictive model based on combination of specific CT findings may elucidate whether ASBO is caused by single bands or matted adhesions and, consequently, influence the clinical pathway. LEVEL OF EVIDENCE: Prognostic study, level IV.


Assuntos
Obstrução Intestinal/etiologia , Intestino Delgado/diagnóstico por imagem , Nomogramas , Aderências Teciduais/diagnóstico , Idoso , Feminino , Humanos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/patologia , Obstrução Intestinal/cirurgia , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Aderências Teciduais/complicações , Aderências Teciduais/patologia , Aderências Teciduais/cirurgia , Tomografia Computadorizada por Raios X
19.
Z Gastroenterol ; 59(4): 326-330, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33845499

RESUMO

T-lymphocytic enteral leiomyositis (T-lel) is a rare disorder causing chronic intestinal pseudo-obstruction (CIPO), with cases predominantly being reported in the field of veterinary and pediatric medicine. Here, we present a case of T-lel-associated CIPO in an adult female, who initially presented with a paralytic ileus 2 weeks after a common gastroenteritis. The histological diagnosis was established through full-thickness bowel biopsy, exhibiting a dense lymphocytic infiltrate in the lamina muscularis of the intestinal wall. This case shows that T-lel can be a cause of chronic intestinal pseudo-obstruction not only in children but also in adults. A subsequent induction of an immunosuppressive therapy with steroids, azathioprine, and ultimately TNF-alpha-inhibiting antibodies led to a slow recovery and stable disease.


Assuntos
Gastroenterite/diagnóstico , Pseudo-Obstrução Intestinal/diagnóstico , Intestino Delgado/patologia , Adulto , Biópsia , Doença Crônica , Feminino , Humanos , Pseudo-Obstrução Intestinal/etiologia
20.
Biomed Res Int ; 2021: 5519144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33884262

RESUMO

Objectives: To explore the application of computed tomography (CT) texture analysis in differentiating lymphomas from other malignancies of the small bowel. Methods: Arterial and venous CT images of 87 patients with small bowel malignancies were retrospectively analyzed. The subjective radiological features were evaluated by the two radiologists with a consensus agreement. The region of interest (ROI) was manually delineated along the edge of the lesion on the largest slice, and a total of 402 quantified features were extracted automatically from AK software. The inter- and intrareader reproducibility was evaluated to select highly reproductive features. The univariate analysis and minimum redundancy maximum relevance (mRMR) algorithm were applied to select the feature subsets with high correlation and low redundancy. The multivariate logistic regression analysis based on texture features and radiological features was employed to construct predictive models for identification of small bowel lymphoma. The diagnostic performance of multivariate models was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The clinical data (age, melena, and abdominal pain) and radiological features (location, shape, margin, dilated lumen, intussusception, enhancement level, adjacent peritoneum, and locoregional lymph node) differed significantly between the nonlymphoma group and lymphoma group (p < 0.05). The areas under the ROC curve of the clinical model, arterial texture model, and venous texture model were 0.93, 0.92, and 0.87, respectively. Conclusion: The arterial texture model showed a great diagnostic value and fitted performance in preoperatively discriminating lymphoma from nonlymphoma of the small bowel.


Assuntos
Processamento de Imagem Assistida por Computador , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/cirurgia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Linfoma/diagnóstico por imagem , Linfoma/cirurgia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Intestinais/patologia , Modelos Logísticos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Análise Multivariada , Cuidados Pré-Operatórios , Adulto Jovem
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