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BACKGROUND: The decision to discontinue intensive care unit (ICU) treatment during the end-oflife stage has recently become a significant concern in Korea, with an observed increase in life-sustaining treatment (LST) withdrawal. There is a growing demand for evidence-based support for patients, families, and clinicians in making LST decisions. This study aimed to identify factors influencing LST decisions in ICU inpatients and to analyze their impact on healthcare utilization. METHODS: We retrospectively reviewed medical records of ICU patients with neurological disorders, infectious disorders, or cancer who were treated at a single university hospital between January 1, 2019 and July 7, 2021. Factors influencing the decision to withdraw LST were compared between those who withdrew LST and those who did not. RESULTS: Among 54,699 hospital admissions, LST was withdrawn in 550 cases (1%). Cancer was the most common diagnosis, followed by pneumonia and cerebral infarction. Among ICU inpatients, LST was withdrawn from 215 (withdrawal group). The withdrawal group was older (78 vs. 75 years, P=0.002), had longer total hospital stays (16 vs. 11 days, P<0.001), and higher ICU readmission rates than the control group. There were no significant differences in the healthcare costs of ICU stay between the two groups. Most LST decisions (86%) were made by family. CONCLUSIONS: The decisions to withdraw LST of ICU inpatients were influenced by age, readmission, and disease category. ICU costs were similar between the withdrawal and control groups. Further research is needed to tailor LST decisions in the ICU.
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Influenza infection induces lung epithelial cell injury via programmed cell death. Glutathione, a potent antioxidant, has been reported to be associated with influenza infection. We hypothesized that lung epithelial cell death during influenza infection is regulated by glutathione metabolism. Eight-week-old male and female BALB/c mice were infected with influenza (PR8: A/PR/8/34 [H1N1]) via intranasal instillation. Metabolomic analyses were performed on whole lung lysate after influenza infection. For in vitro analysis, Beas-2B cells were infected with influenza. RNA was extracted, and QuantiTect Primer Assay was used to assess gene expression. Glutathione concentrations were assessed by colorimetric assay. Influenza infection resulted in increased inflammation and epithelial cell injury in our murine model, leading to increased morbidity and mortality. In both our in vivo and in vitro models, influenza infection was found to induce apoptosis and necroptosis. Influenza infection led to decreased glutathione metabolism and reduced glutathione reductase activity in lung epithelial cells. Genetic inhibition of glutathione reductase suppressed apoptosis and necroptosis of lung epithelial cells. Pharmacologic inhibition of glutathione reductase reduced airway inflammation, lung injury, and cell death in our murine influenza model. Our results demonstrate that glutathione reductase activity is suppressed during influenza. Glutathione reductase inhibition prevents epithelial cell death and morbidity in our murine influenza model. Our results suggest that glutathione reductase-dependent glutathione metabolism may play an important role in the host response to viral infection by regulating lung epithelial cell death.
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Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Lesão Pulmonar , Infecções por Orthomyxoviridae , Animais , Antioxidantes/metabolismo , Feminino , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Humanos , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/metabolismo , Pulmão/metabolismo , Lesão Pulmonar/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/metabolismo , RNA/metabolismoRESUMO
Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the common reasons that colorectal cancer patients cannot maintain their routine chemotherapy schedules. Some medications are used for pain relief; however, the effect of medication is disappointing. We carried out this study to confirm that a rehabilitation program using minor muscles might provide a valuable aid in symptom relief of CIPN. Methods: Eleven colorectal cancer patients participated in the basic craftwork program which encouraged the use of the minor muscles of the hands to make and decorate the handicrafts and it was held for 2 hours once a week, for a total of four times. There were no limitations in the stage of cancer or types of chemotherapy to participate the program. Questionnaires were obtained from participants before and after the basic handicrafts program. Results: Of the 11 patients (3 men, 8 women; mean age, 53.0±11.2 years), six received 5-fluorouracil (5-FU) chemotherapy, four received FOLFOX4 (combination of 5-FU, leucovorin, and oxaliplatin) chemotherapy, and one received 5-FU, FOLFOX4, and FOLFIRI (combination of 5-FU, leucovorin, and irinotecan) chemotherapy sequentially. Patients attended the program a mean of 3.8±0.4 times. Common symptoms of CIPN were "throbbing pain," "aching pain," and "numbness." The mean score of the questionnaires between pre- and post-program was 34.1±31.7 points and 24.4±21.5 points each, and it was significantly decreased (P=0.040). Conclusion: Patients often suffered from CIPN symptoms like throbbing or aching pain and numbness during their adjuvant chemotherapy. A rehabilitation program using minor muscles for CIPN is expected to be effective.
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BACKGROUND: This study examined the experience of withholding or withdrawing life-sustaining treatment in patients hospitalized in the intensive care units (ICUs) of a tertiary care center. It also considers the role that intensivists play in the decision-making process regarding the withdrawal of life-sustaining treatment. METHODS: We retrospectively analyzed the medical records of 227 patients who decided to withhold or withdraw life-sustaining treatment while hospitalized at Ewha Womans University Medical Center Mokdong between April 9 and December 31, 2018. RESULTS: The 227 hospitalized patients included in the analysis withheld or withdrew from life-sustaining treatment. The department in which life-sustaining treatment was withheld or withdrawn most frequently was hemato-oncology (26.4%). Among these patients, the most common diagnosis was gastrointestinal tract cancer (29.1%). A majority of patients (64.3%) chose not to receive any life-sustaining treatment. Of the 80 patients in the ICU, intensivists participated in the decision to withhold or withdraw life-sustaining treatment in 34 cases. There were higher proportions of treatment withdrawal and ICU-to-ward transfers among the cases in whom intensivists participated in decision making compared to those cases in whom intensivists did not participate (50.0% vs. 4.3% and 52.9% vs. 19.6%, respectively). CONCLUSIONS: Through their participation in end-of-life discussions, intensivists can help patients' families to make decisions about withholding or withdrawing life-sustaining treatment and possibly avoiding futile treatments for these patients.
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Silkworm, Bombyx mori, contains high amounts of beneficial nutrients, including amino acids, proteins, essential minerals, and omega-3 fatty acids. We have previously reported a technique for producing steamed and freeze-dried mature silkworm larval powder (SMSP), which makes it easier to digest mature silkworm. In this study, we investigated the preventive effects of SMSP on alcoholic fatty liver disease and elucidated its mechanism of action. Male Sprague-Dawley rats treated with SMSP (50 mg/kg) or normal diet (AIN-76A) were administered 25% ethanol (3 g/kg body weight) by oral gavage for 4 weeks. SMSP administration for 4 weeks significantly decreased hepatic fat accumulation in ethanol-treated rats by modulating lipogenesis and fatty acid oxidation-related molecules such as sirtuin 1, AMP-activated protein kinase, and acetyl-CoA carboxylase 1. Moreover, SMSP administration significantly diminished the levels of triglyceride in liver tissues by as much as 35%, as well as lowering the serum levels of triglyceride, gamma glutamyl transpeptidase, alanine transaminase, and aspartate aminotransferase in ethanol-treated rats. SMSP supplementation also decreased the pro-inflammatory tumor necrosis factor-alpha and interleukin 1 beta levels and cytochrome P450 2E1 generating oxidative stress. These results suggest that SMSP administration may be possible for the prevention of alcoholic liver disease.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive, fatal lung disease that affects older adults. One of the detrimental natural histories of IPF is acute exacerbation of IPF (AE-IPF), of which bacterial infection is reported to play an important role. However, the mechanism by which bacterial infection modulates the fibrotic response remains unclear. OBJECTIVES: Altered glucose metabolism has been implicated in the pathogenesis of fibrotic lung diseases. We have previously demonstrated that glucose transporter 1 (GLUT1)-dependent glycolysis regulates fibrogenesis in a murine fibrosis model. To expand on these findings, we hypothesised that GLUT1-dependent glycolysis regulates acute exacerbation of lung fibrogenesis during bacterial infection via AIM2 inflammasome activation. RESULTS: In our current study, using a murine model of Streptococcus pneumoniae (S. pneumoniae) infection, we investigated the potential role of GLUT1 on mediating fibrotic responses to an acute exacerbation during bleomycin-induced fibrosis. The results of our current study illustrate that GLUT1 deficiency ameliorates S. pneumoniae-mediated exacerbation of lung fibrosis (wild type (WT)/phosphate buffered saline (PBS), n=3; WT/S. pneumoniae, n=3; WT/Bleomycin, n=5 ; WT/Bleomycin+S. pneumoniae, n=7; LysM-Cre-Glut1fl/f /PBS, n=3; LysM-Cre-Glut1fl/fl /S. pneumoniae, n=3; LysM-Cre-Glut1fl/fl /Bleomycin, n=6; LysM-Cre-Glut1fl/fl /Bleomycin+S. pneumoniae, n=9, p=0.041). Further, the AIM2 inflammasome, a multiprotein complex essential for sensing cytosolic bacterial DNA as a danger signal, is an important regulator of this GLUT1-mediated fibrosis and genetic deficiency of AIM2 reduced bleomycin-induced fibrosis after S. pneumoniae infection (WT/PBS, n=6; WT/Bleomycin+S. pneumoniae, n=15; Aim2-/-/PBS, n=6, Aim2-/-/Bleomycin+S. pneumoniae, n=11, p=0.034). GLUT1 deficiency reduced expression and function of the AIM2 inflammasome, and AIM2-deficient mice showed substantial reduction of lung fibrosis after S. pneumoniae infection. CONCLUSION: Our results demonstrate that GLUT1-dependent glycolysis promotes exacerbation of lung fibrogenesis during S. pneumoniae infection via AIM2 inflammasome activation.
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Transportador de Glucose Tipo 1/metabolismo , Glicólise , Fibrose Pulmonar Idiopática/metabolismo , Inflamassomos/metabolismo , Pulmão/patologia , Infecções Pneumocócicas/metabolismo , Animais , Bleomicina , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Técnicas de Inativação de Genes , Transportador de Glucose Tipo 1/genética , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/patologia , Inflamassomos/genética , Camundongos , Infecções Pneumocócicas/complicaçõesRESUMO
The apnea test is an essential examination for the determination of brain death; however, hypotension, hypoxemia, and other complications during the apnea test can affect the stability of brain-dead patients, as well as organ function for recipients. Therefore, it is necessary to establish standard guidelines for apnea testing.The modified apnea test (MAT) comprises delivery of 100% oxygen through the endotracheal tube connected to manual resuscitator (Ambu bag) with the positive end-expiratory pressure (PEEP) valve after disconnection of the mechanical ventilator for maintenance of PEEP. Forty-nine instances of the conventional apnea test (CAT) were performed in 25 brain-dead patients; 77 instances of the MAT were performed in 39 brain-dead patients.The mean duration of the apnea test was 3.5â±â1.4âminutes in the CAT group and 3.0â±â1.2âminutes in the MAT group. There were no significant changes in PaCO2, PaO2, or pH between the CAT and MAT groups (Pâ=â.341, .593, and .503, respectively). In overweight patients (body mass index ≥ 23âkg/m), MAT prevented dramatic reductions in PaO2 and SaO2 (Pâ<â.05 for both). In the patients who had hypoxic brain injury due to hanging, differences in PaO2 and SaO2 in the MAT group were significantly smaller than in the CAT group (Pâ<â.05).Although MAT, which was invented to maintain PEEP, was not efficient for all brain-dead patients, it could be helpful in selected patient groups, such as overweight patients or those who had hypoxic injury due to hanging. And clinicians should consider short-term apnea test to avoid unnecessarily prolonged hypoxemia.
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Apneia/diagnóstico , Gasometria/métodos , Morte Encefálica/diagnóstico , Respiração com Pressão Positiva/métodos , Apneia/complicações , Feminino , Humanos , Hipóxia Encefálica/complicações , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicaçõesRESUMO
BACKGROUND: Integrins play a critical role in carcinogenesis. Integrin ß1 localization is regulated by the guanosine-5'-triphosphate hydrolase Rab25 and integrin ß1 levels are elevated in the serum of colon cancer patients; thus, the present study examined the effects of epidermal growth factor (EGF) and Rab25 on integrin ß1 localization in colon cancer cells. METHODS: HCT116 human colon cancer cells were treated with increasing concentrations of EGF, and cell proliferation and protein expression were monitored by MTT and western blot analyses, respectively. Cell fractionation was performed to determine integrin ß1 localization in the membrane and cytosol. Integrin ß1 extracellular shedding was monitored by enzyme-linked immunosorbent assays (ELISAs) with culture supernatants from stimulated cells. HCT116 cells were transfected with Rab25-specific siRNA to determine the significance of Rab25 in integrin ß1 trafficking in the presence of EGF. RESULTS: Total integrin ß1 expression increased in response to EGF and subsequently decreased at 24 h post-stimulation. A similar decrease was observed in purified membrane fractions, whereas no changes were observed in cytosolic levels. ELISAs using media from stimulated cell cultures demonstrated increased integrin ß1 levels corresponding to the decrease observed in membrane fractions, suggesting that EGF induces integrin receptor shedding. EGF stimulation in Rab25-knockdown cells resulted in integrin ß1 accumulation in the membrane, suggesting that Rab25 promotes integrin endocytosis. CONCLUSIONS: Integrin ß1 is shed from colon cancer cells in response to EGF stimulation in a Rab25-dependent manner. These results further the present understanding of the role of integrin ß1 in colon cancer progression.
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BACKGROUND: Helicobacter pylori, a gram-negative bacterium, is the causative agent of gastric disorders and gastric cancer in the human stomach. Vacuolating cytotoxin A (VacA) is among the multi-effect protein toxins released by H. pylori that enables its persistence in the human stomach. METHODS: To evaluate the effect of anti-VacA egg yolk immunoglobulin (anti-VacA IgY) on H. pylori infection, a highly specific anti-VacA IgY was produced from egg yolks of hens immunized with a mixture of two purified recombinant VacAs. Female C57BL/6 mice were supplemented anti-VacA IgY daily with drinking water for 2â¯weeks before and 4â¯weeks after H. pylori ATCC 43504 inoculation. Anti-VacA IgY recognized both native and denatured structures of VacA by enzyme-linked immunosorbent assay and immunoblotting analyses, respectively. RESULTS: Oral administration of anti-VacA IgYs significantly (pâ¯<â¯.05) reduced the serum levels of anti-H. pylori antibodies compared to those in the H. pylori-infected, untreated group. The reduction in the immune response was accompanied by a significant (pâ¯<â¯.05) decrease in eosinophilic infiltration of the stomach in anti-VacA IgY treated group compared to other groups. Concomitantly, H. pylori-induced histological changes and H. pylori antigen-positivity in gastric tissues were decreased significantly (pâ¯<â¯.05) in anti-VacA IgY treated group similar to the control group. CONCLUSIONS: Oral administration of anti-VacA IgY is correlated with a protective effect against H. pylori colonization and induced histological changes in gastric tissues. Our experimental study has proved that it is expected to be a new drug candidate of Hp infection by further study.
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Anticorpos Antibacterianos/administração & dosagem , Proteínas de Bactérias/antagonistas & inibidores , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/imunologia , Imunoglobulinas/administração & dosagem , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Camundongos Endogâmicos C57BL , Resultado do TratamentoRESUMO
Fournier's gangrene is a gas-forming, necrotising soft tissue infection affecting the perineum. It spreads rapidly along the deep fascial planes and is associated with a high mortality rate. With a growing elderly population with comorbidities, the frequency of severe cases of Fournier's gangrene is expected to increase. We retrospectively reviewed 20 patients diagnosed with Fournier's gangrene at our institution from 2003 to 2014 and analysed data. Thirteen patients had diabetes mellitus, two had been diagnosed with liver cirrhosis, and four were chronic alcoholics. Of 15 patients admitted to an intensive care unit, 11 underwent colostomy, and 4 required skin grafts for wound healing. The wide wounds of two patients were healed using vacuum-assisted closure (VAC® ) dressing without additional surgery. The mortality rate was 25%, and the patients whose Fournier's gangrene severity index (FGSI) score was higher than 9 points or whose blood urea nitrogen (BUN) level was higher than 50 mg/dl had a poor prognosis. In order to treat Fournier's gangrene, aggressive surgical treatment, including wide debridement and stoma creation, should be considered as soon as possible to improve survival rates. Additionally, VAC dressing is helpful in healing the wide debridement wound without additional reconstructive surgery.
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Desbridamento/métodos , Gangrena de Fournier/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Períneo/fisiopatologia , Infecções dos Tecidos Moles/terapia , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy.
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PURPOSE: The assurance of a negative resection margin is significant in rectal cancer as it indicates a reduced risk of local recurrence; thus, sufficient length of the resection margin is strongly required. The purpose of this study was to analyze the relationship between the length of the distal resection margin (DRM) and local recurrence or survival rate and to evaluate the possibility of performing sphincter-conserving surgery. METHODS: The medical records of 218 rectal cancer patients were analyzed. Patients were classified into three groups according to the length of the DRM as follows: group 1, DRM < 1 cm; group 2, 1 cm ≤ DRM ≤ 2 cm; and group 3, DRM > 2 cm. RESULTS: Of 218 patients enrolled, 81 were in group 1, 66 in group 2, and 71 in group 3. The 5-year survival rates were 78.2%, 78.2%, and 76.8% for groups 1, 2, and 3, respectively, and there were no statistically significant differences in survival (P = 0.913). Local recurrence was found in 2 patients in group 1, 1 patient in group 2, and 1 patient in group 3; there were no statistically significant differences in local recurrence (P = 0.908). CONCLUSION: A DRM of < 1 cm did not impair the oncologic outcomes of rectal cancer patients. Our results indicated that surgeons should keep in mind to consider the option of sphincter-conserving surgery with adjuvant chemoradiotherapy even in very low rectal cancer.
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PURPOSE: Chest computed tomography is performed frequently for the preoperative pulmonary staging in colorectal cancers (CRCs) regardless of the result of chest x-ray (CXR) due to its high sensitivities and specificities. The advancement of CT technology detects more indeterminate lung lesions that may require further investigations, referrals and follow-up. The aim of this study was to suggest a guideline for performing chest CT for preoperative pulmonary staging in colorectal cancer. METHODS: We performed a retrospective analysis of the records of patients who had chest CT preformed without the evidence of metastasis on CXR for preoperative pulmonary staging. RESULTS: Of 21 patients with metastatic nodules on chest CT, 23.8% showed pulmonary metastasis on positron emission tomography, 47.6% showed extrapulmonary metastasis on preoperative evaluation and 61.9% showed elevated serum carcinoembryonic antigen level above 10 ng/mL. These results showed significant value compared to patients without metastatic nodules. But, in analyzing patients with or without indeterminate nodules in the three contents listed above, there was no significance. CONCLUSION: In the patients with CRC who show normal CXR and exhibit positivity in PET, preoperative extrapulmonary metastasis and elevated serum CEA level above 10 ng/mL preoperatively, chest CT would be helpful in preoperative staging.
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OBJECTIVE: In spite of cytoprotective and anti-inflammatory actions, conventional licorice extracts (c-lico) were limitedly used due to serious side effects of glycyrrhizin. As our group had successfully isolated special licorice extracts (s-lico) lowering troublesome glycyrrhizin, but increasing licochalcone A, we have compared anti-inflammatory, antioxidative, and cytoprotective actions of s-lico and c-lico against either in vitro or in vivo Helicobacter pylori infection. METHODS: RT-PCR and Western blot were performed to check anti-inflammatory action and electron spin resonance (ESR) and DCFDA spectroscopy to check antioxidative action. s-lico or c-lico was pretreated 1 hours before H. pylori infection on AGS cells. Interleukin-10 deficient mice inoculated H. pylori and followed with high salt containing pallet diets to produce H. pylori-associated chronic atrophic gastritis and gastric tumors, during which s-lico or c-lico-containing pellet diets were administered up to 24 weeks. RESULTS: s-lico had fabulous efficacy on scavenging ROS which was further confirmed by DCFDA study and ESR measurement. The expressions of COX-2, iNOS, VEGF, and IL-8 were increased after H. pylori infection, of which levels were significantly decreased with s-lico in a dose-dependent manner. s-lico significantly ameliorated hypoxia-induced or H. pylori-induced angiogenic activities. s-lico significantly ameliorated H. pylori-induced gastric damages as well as gastritis. Our animal model showed significant development of gastric tumors including adenoma and dysplasia relevant to H. pylori infection, and s-lico administration significantly attenuated incidence of H. pylori-induced gastric tumorigenesis. CONCLUSIONS: Special licorice extracts can be anticipating substance afforded significant attenuation of either H. pylori-induced gastritis or tumorigenesis based on potent antioxidative, anti-inflammatory, and antimutagenic actions.
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Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Dieta/métodos , Glycyrrhiza/química , Infecções por Helicobacter/complicações , Extratos Vegetais/uso terapêutico , Neoplasias Gástricas/prevenção & controle , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Carcinogênese/efeitos dos fármacos , Chalconas/análise , Ácido Glicirrízico/análise , Masculino , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Resultado do TratamentoRESUMO
PURPOSE: Lymph-node metastasis is considered as critical prognostic factor in colorectal cancer. A preoperative evaluation of lymph-node metastasis can also help to determine the range of distant lymph node dissection. However, the reliability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the detection of lymph-node metastasis is not fully known. METHODS: The medical records of 433 patients diagnosed with colorectal cancer were reviewed retrospectively. FDG-PET/CT and CT were performed on all patients. Lymph nodes were classified into regional and distant lymph nodes according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition. RESULTS: The patients included 231 males (53.3%) and 202 females (46.7%), with a mean age of 64.7 ± 19.0 years. For regional lymph nodes, the sensitivity of FDG-PET/CT was lower than that of CT (57.1% vs. 73.5%, P < 0.001). For distant lymph nodes, the sensitivity of FDG-PET/CT was higher than that of CT (64.7% vs. 52.9%, P = 0.012). The sensitivity of FDG-PET/CT for regional lymph nodes was higher in patients with larger primary tumors. The positivity of lymph-node metastasis for FDG-PET/CT was affected by carcinoembryonic antigen levels, tumor location, and cancer stage for regional lymph nodes and by age and cancer stage for distant lymph nodes (P < 0.05). CONCLUSION: The sensitivity of FDG-PET/CT for regional lymph-node metastasis was not superior to that of CT. However, FDG-PET/CT provides helpful information for determining surgical plan especially in high risk patients group.
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PURPOSE: Adjuvant chemotherapy is routinely recommended for locally advanced colorectal cancer (CRC). There are very few data for the optimal starting date of adjuvant chemotherapy after the surgery. This study aimed to evaluate the effectiveness of earlier adoption of adjuvant chemotherapy after curative surgery for stage III CRC. METHODS: In this study, 159 patients with stage III CRC, who had undergone a curative resection, were enrolled retrospectively. Patients were categorized into 3 groups representing different timings to initiate the chemotherapy; less than 2 weeks (group 1), 3 to 4 weeks (group 2), and more than 5 weeks (group 3). The overall survival rate (OS) and the relapse-free survival rate (RFS) were analyzed to evaluate the effectiveness of adjuvant chemotherapy. RESULTS: The 5-year OSs of the patients were 73.7% in group 1, 67.0% in group 2, and 55.2% in group 3. The 5-year RFSs of the patients were 48.8% in group 1, 64.7% in group 2, and 57.1% in group 3. There were no significant differences in either the OS or the RFS (P = 0.200, P = 0.405). CONCLUSION: Starting chemotherapy earlier than 6 weeks after surgery does not show any significant difference. Thus, although adjuvant chemotherapy should preferably begin within 6 weeks, the starting date should not necessarily be hastened, and the patient's general condition should be taken into consideration.
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PURPOSE: Recently many cases of appendectomy have been conducted by single-incision laparoscopic technique. The aim of this study is to figure out the benefits of transumbilical single-port laparoscopic appendectomy (TULA) compared with conventional three-port laparoscopic appendectomy (CTLA). METHODS: From 2010 to 2012, 89 patients who were diagnosed as acute appendicitis and then underwent laparoscopic appendectomy a single surgeon were enrolled in this study and with their medical records were reviewed retrospectively. Cases of complicated appendicitis confirmed on imaging tools and patients over 3 points on the American Society of Anesthesia score were excluded. RESULTS: Among the total of 89 patients, there were 51 patients in the TULA group and 38 patients in the CTLA group. The visual analogue scale (VAS) of postoperative day (POD) #1 was higher in the TULA group than in the CTLA group (P = 0.048). The operative time and other variables had no statistical significances (P > 0.05). CONCLUSION: Despite the insufficiency of instruments and the difficulty of handling, TULA was not worse in operative time, VAS after POD #2, and the total operative cost than CTLA. And, if there are no disadvantages of TULA, TULA may be suitable in substituting three-port laparoscopic surgery and could be considered as one field of natural orifice transluminal endoscopic surgery with the improvement and development of the instruments and revised studies.
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Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG-containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG-treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and ß-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC.
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Anticarcinógenos/farmacologia , Colite/complicações , Neoplasias Colorretais/complicações , Neoplasias Colorretais/prevenção & controle , Desoxiguanosina/análogos & derivados , Neoplasias/prevenção & controle , 8-Hidroxi-2'-Desoxiguanosina , Animais , Azoximetano/farmacologia , Desoxiguanosina/farmacologia , Dextranos/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Inflamação , Interleucina-10/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Transcrição STAT3/metabolismo , Sulfatos/farmacologiaRESUMO
ENA Actimineral Resource A (ENA-A) is alkaline water that is composed of refined edible cuttlefish bone and two different species of seaweed, Phymatolithon calcareum and Lithothamnion corallioides. In the present study, ENA-A was investigated as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in rats. Liver injury was induced by either subacute or chronic CCl(4) administration, and the rats had free access to tap water mixed with 0% (control group) or 10% (v/v) ENA-A for 5 or 8 weeks. The results of histological examination and measurement of antioxidant activity showed that the reactive oxygen species production, lipid peroxidation, induction of CYP2E1 were decreased and the antioxidant activity, including glutathione and catalase production, was increased in the ENA-A groups as compared with the control group. On 2-DE gel analysis of the proteomes, 13 differentially expressed proteins were obtained in the ENA-A groups as compared with the control group. Antioxidant proteins, including glutathione S-transferase, kelch-like ECH-associated protein 1, and peroxiredoxin 1, were increased with hepatocyte nuclear factor 3-beta and serum albumin precursor, and kininogen precursor decreased more in the ENA-A groups than compared to the control group. In conclusion, our results suggest that ENA-A does indeed have some protective capabilities against CCl(4)-induced liver injury through its antioxidant function.
Assuntos
Antioxidantes/farmacologia , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Minerais/farmacologia , Preparações de Plantas/farmacologia , Animais , Catalase/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Eletroforese em Gel Bidimensional , Indução Enzimática/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Proteína 1 Associada a ECH Semelhante a Kelch , Peroxidação de Lipídeos/efeitos dos fármacos , Espectrometria de Massas , Estresse Oxidativo/efeitos dos fármacos , Peroxirredoxinas/metabolismo , Proteínas/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.