RESUMO
PURPOSE: Few studies have reported on the interactions between gastrectomy and antithrombotic therapy, especially the long-term prognosis. We aimed to clarify the short- and long-term prognosis of gastrectomy for patients on antithrombotic therapy. METHODS: We reviewed the perioperative data and survival rate of patients who underwent laparoscopic distal gastrectomy (LDG) at our institute between 2010 and 2013. RESULTS: There were 119 patients enrolled in this retrospective study: 31 who were taking antithrombotic drugs (antithrombotic therapy (ATT) group), and 88 who were not (non-ATT group). The mean age was significantly higher in the ATT group than in the non-ATT group. No significant differences were observed in the amount of intraoperative bleeding or blood hemoglobin level after surgery between the groups. Bleeding complications occurred in only one patient from the ATT group, and the postoperative complication rate was comparable between the groups. During follow-up, cerebrovascular or cardiovascular events developed in 19.4% of the ATT group patients and 4.5% of the non-ATT group patients; however, there were no significant differences in the 5-year overall survival rates between the groups (ATT group, 76.9%; non-ATT group, 82.9%). CONCLUSIONS: Antithrombotic therapy did not affect the short-term or long-term prognosis of patients after LDG.
Assuntos
Laparoscopia , Neoplasias Gástricas , Fibrinolíticos , Gastrectomia/efeitos adversos , Hemoglobinas , Humanos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The results showed that 100% of rats with C6-L tumors developed lung metastases, while metastases were found in only 44% of rats with C6-S tumors (nâ¯=â¯25). Tumors disappeared in approximately 20% of the C6-S-bearing rats, and these animals evaded death 180â¯d after transplantation, while all C6-L tumor-bearing rats died after 45â¯d. Next generation sequencing revealed that C6-S tumors expressed chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry revealed that C6-S tumors contained more dead cells and more CD45+ cells, including natural killer cells and CD8+ lymphocytes. In particular, multiple subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were more abundant in C6-S than in C6-L tumors. These results suggested that CD200S induced the accumulation of multiple dendritic cell subsets that activated cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells.
Assuntos
Antígenos CD/imunologia , Glioma/imunologia , Glioma/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Animais , Antígenos CD/genética , Células Dendríticas/imunologia , Células Dendríticas/patologia , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Tolerância Imunológica , Imunidade Celular , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Ratos Wistar , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologiaRESUMO
An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level.
Assuntos
Anti-Inflamatórios/farmacologia , Bromisoval/farmacologia , Hipnóticos e Sedativos/farmacologia , Microglia/efeitos dos fármacos , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Citocinas/metabolismo , Complexo II de Transporte de Elétrons/antagonistas & inibidores , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/genética , Janus Quinase 1/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fosforilação , Ratos Wistar , Rotenona/farmacologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismoRESUMO
BACKGROUND: Elderly patients usually have concurrent ailments, and the safety and effectiveness of laparoscopy-assisted distal gastrectomy (LADG) for these patients have been controversial. This study aimed to evaluate whether laparoscopy-assisted distal gastrectomy is safe and effective for elderly patients aged 80 years and over, as well as to clarify their long-term prognosis. METHODS: A total of 31 patients aged 80 years and over who underwent LADG in our hospital were retrospectively reviewed. Peri- and postoperative data were compared with those of 38 patients aged 65 years and younger. The median follow-up period of the elderly and younger group was 56.0 and 63.0 months, respectively, and their prognosis was examined. RESULTS: There were significant differences between the two groups in preoperative respiratory and renal functions, hemoglobin, and nutritional index. Significant differences in postoperative complications were seen only in pneumonia and delirium. There were no hospital deaths, but the 3-year and 5-year overall survival rates were significantly lower in the elderly group than in the non-elderly group. However, in the elderly group, only one patient died of gastric cancer recurrence, whereas four died of cardiovascular disease and three died of pneumonia during follow-up. Therefore, the recurrence-free survival rate was not significantly different between the groups. CONCLUSIONS: LADG seems to be safe and effective even for elderly patients, and their prognosis was satisfactory. However, careful monitoring for cardiovascular and pulmonary disease should be observed during the follow-up period.
Assuntos
Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Fatores Etários , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Sepsis is a severe pathologic event, frequently causing death in critically ill patients. However, there are no approved drugs to treat sepsis, despite clinical trials of many agents that have distinct targets. Therefore, a novel effective treatment should be developed based on the pathogenesis of sepsis. We recently observed that an old hypnotic drug, bromvalerylurea (BU) suppressed expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-γ activated alveolar and peritoneal macrophages (AMs and PMs). Taken the anti-inflammatory effects of BU on macrophages, we challenged it to septic rats that had been subjected to cecum-ligation and puncture (CLP). BU was subcutaneously administered to septic rats twice per day. Seven days after CLP treatment, 85% of septic rats administrated vehicle had died, whereas administration of BU reduce the rate to 50%. Septic rats showed symptoms of multi-organ failure; respiratory, circulatory and renal system failures as revealed by histopathological analyses, blood gas test and others. BU ameliorated these symptoms. BU also prevented elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Collectively, BU might be a novel agent to ameliorate sepsis by preventing the onset of MOF.
Assuntos
Bromisoval/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Sepse/tratamento farmacológico , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Proteínas I-kappa B/metabolismo , Interferon gama/metabolismo , Interleucina-6/sangue , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Insuficiência de Múltiplos Órgãos/patologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Transcrição STAT1/metabolismo , Sepse/etiologia , Sepse/fisiopatologiaRESUMO
PURPOSE: Cholecystectomy can become hazardous when inflammation develops, leading to anatomical changes in Calot's triangle. We attempted to study the safety and efficacy of laparoscopic subtotal cholecystectomy (LSC) to decrease the incidence of complications and the rate of conversion to open surgery. METHODS: Patients who underwent LSC between January 2005 and December 2008 were evaluated retrospectively. The operations were performed laparoscopically irrespective of the grade of inflammation estimated preoperatively. However, patients with severe inflammation of the gallbladder underwent LSC involving resection of the anterior wall of the gallbladder, removal of all stones and placement of an infrahepatic drainage tube. To prevent intraoperative complications, including bile duct injury, intraoperative cholangiography was performed. RESULTS: LSC was performed in 26 elective procedures among 26 patients (eight females, 18 males). The median patient age was 69 years (range 43-82 years). The median operative time was 125 min (range 60-215 min) and the median postoperative inpatient stay was 6 days (range 3-21 days). Cholangiography was performed during surgery in 24 patients. One patient underwent postoperative endoscopic sphincterotomy for a retained common bile duct stone that was found on cholangiography during surgery. Neither complications nor conversion to open surgery were encountered in this study. CONCLUSIONS: LSC with the aid of intraoperative cholangiography is a safe and effective treatment for severe cholecystitis.
Assuntos
Colangiografia , Colecistectomia Laparoscópica/métodos , Colecistite/cirurgia , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Período Intraoperatório , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Segurança , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
A rectovaginal fistula (RVF) is an abnormal tract between the rectum and vagina, which requires surgical intervention in many cases. Although there are many different therapeutic approaches for RVF depending on the patient's' condition, there are no established guidelines for the care of RVF. This study aimed to evaluate the results of laparoscopic colostomy in advanced cancer patients with RVF, and the safety and efficacy of this surgery. In this study, seven female advanced cancer patients with RVF were hospitalized and successfully treated with laparoscopic colostomy from 2015 to 2018 at our university hospital. Their data were retrospectively evaluated from their medical records. The early use of diverting stomas facilitated timely resumption of cancer treatment and enabled early treatment with chemotherapy or radiotherapy. Although vaginal stool leakage affected three patients, all patients recovered, experiencing neither pain nor infection during their cancer treatment. While colostomy was physically and mentally taxing for the patients, it improved the infection and pain caused by the RVF. We conclude that the early use of diverting stomas had two effects: a significant improvement in infection management and facilitation of the rapid resumption of cancer treatment.
RESUMO
There are many reports on the positional relationship between the ileocolic artery and superior mesenteric vein (SMV). However, there have been no reports of anomalous venous confluence in the ileocecal vessel area. A 69-year-old man was diagnosed with cecal cancer on a preoperative examination of a lung tumor. We planned to perform surgery for the cecal cancer. Computed tomography angiography revealed an anomalous vein confluence in the ileocolic region. We performed robot-assisted ileocecal resection. Although the small intestinal vein was misidentified as the SMV at first, we confirmed the misidentification, identified the SMV on the dorsal side of the ileocolic artery, and ligated the ileocolic vessels with precise forceps manipulation during robotic surgery. Especially for cases with vascular anomalies revealed by preoperative computed tomography angiography, robotic surgery may be useful, as flexible forceps manipulation prevents vascular injury.
Assuntos
Neoplasias do Ceco , Neoplasias , Robótica , Masculino , Humanos , Idoso , Ceco , Veias Mesentéricas/cirurgiaRESUMO
Background: Endoscopic surgery also has been becoming widespread in the field of pediatric surgery. However, most disease treated by pediatric surgery in a single institution are small number of cases. Besides, the variety of operative procedures that need to be performed in this field is quite wide. For these reasons, pediatric surgeons have limited opportunities to perform endoscopic surgery. Therefore, it is difficult to introduce advanced endoscopic surgery at a single local hospital. To educate pediatric surgeons in local hospitals, for widespread advanced pediatric endoscopic surgery safely, and to eliminate the need for patient centralization, we have introduced a proctoring system. We compared the surgical results of our institution, a center hospital, with other local institutions, to investigate the feasibility of our proctoring system. Methods: The experienced pediatric surgeon of our institution visits local hospitals to provide onsite coaching and supervises pediatric surgeons on the learning curve. All patients who underwent laparoscopic cyst excision and hepaticojejunostomy for choledochal cysts, one of the advanced pediatric endoscopic surgeries was retrospectively reviewed. Results: Thirty-four cases were evaluated (14 cases in our institution, 20 cases in 9 other institutions). The procedures of all 34 cases were performed by surgeons with 0-2 cases of experience in the procedure. There were no open conversion cases. There was no significant difference in the operative date. There was 1 case (6.7%) of postoperative complications during hospitalization at our institution and 3 cases (14.3%) at other institutions (P = .47). Two cases of late complications (13.3%) occurred at our institution, whereas 6 cases (28.6%) occurred at other institutions (P = .28). Conclusion: With the proctoring system, the performance and completion of advanced pediatric endoscopic surgery at local institutions was feasible. This has important implications given the ever-growing demand for pediatric endoscopic surgery and the increasing need for competent pediatric endoscopic surgeons.
Assuntos
Cisto do Colédoco , Laparoscopia , Criança , Humanos , Cisto do Colédoco/cirurgia , Estudos Retrospectivos , Laparoscopia/métodos , Anastomose Cirúrgica , Fígado/cirurgia , Resultado do TratamentoRESUMO
Iliopsoas abscess (IPA) is rare in children, particularly in neonates. A male neonate was born at 38 weeks of gestation with a weight of 2915 g. On day 22 after birth, his family noticed that his right thigh was swollen. Abdominal computed tomography showed a mass extending to the right iliopsoas from the right thigh with thick septa. Puncture to the right groin yielded purulent fluid, and so a diagnosis of abscess was made. The puncture was followed by surgical drainage through a small inguinal incision, and the abscess cavity was irrigated thoroughly using normal saline. Culture of abscess fluid was positive for Streptococcus pneumoniae, so intravenous ABPC infusion was continued. The postoperative magnetic resonance imaging indicate that the IPA was derived from arthritis of the hip, and the patients received Riemenbügel for the incomplete hip dislocation. He is doing well at 2 years of age.
Assuntos
Abscesso do Psoas/diagnóstico por imagem , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/uso terapêutico , Drenagem , Humanos , Recém-Nascido , Masculino , Abscesso do Psoas/tratamento farmacológico , Abscesso do Psoas/cirurgia , Radiografia , Resultado do TratamentoRESUMO
Indocyanine green (ICG) fluorescence angiography has recently been reported useful as a method for predicting intestinal blood flow and may reduce anastomotic leakage. However, the quantification method for ICG fluorescence angiography has not been established. We usually measure the tissue oxygen saturation (StO2 ) in the intestinal tract via near-infrared spectroscopy, as it is able to measure the oxygen concentration accurately and immediately shows objective data. In this study, we propose that the time to reach the anastomotic site after intravenous ICG injection is an effective parameter for quantifying ICG fluorescence angiography from the comparison to the data of StO2 in the intestinal tract.
Assuntos
Verde de Indocianina , Saturação de Oxigênio , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Angiofluoresceinografia/efeitos adversos , Humanos , Projetos PilotoRESUMO
BACKGROUND: The increasing age of patients with severe motor and intellectual disabilities (SMID) has become a serious concern. Few studies have investigated tumor treatment in this population. METHODS: Tumor treatments for 12 SMID patients were examined. RESULTS: Blood tests and ultrasonography were useful for screening. With regard to treatment, surgery for SMID patients was performed in the same manner as for patients without SMID, and the results were generally satisfactory, without major complications. Typically, cancer was diagnosed at an advanced stage, and many metachronous double cancers were observed. CONCLUSIONS: Treatment yielded satisfactory results for patients with SMID and their families. Future studies should examine the clinical significance of screening and tumor operative method for patients with SMID.
Assuntos
Deficiência Intelectual , Previsões , Humanos , Incidência , Deficiência Intelectual/complicações , Deficiência Intelectual/epidemiologiaRESUMO
BACKGROUND/AIMS: Acute respiratory distress syndrome (ARDS) occasionally occurs after gastrointestinal surgery involving severe inflammation such as diffuse peritonitis. Management of this condition has been difficult and effective therapies have not yet been established. In the present study the management for ARDS after gastrointestinal surgery was evaluated. METHODOLOGY: A total of 15 patients developed ARDS after gastrointestinal operations performed in our institution. The mean patient age was 75.4±11.1 years. Onset of ARDS occurred ≤24 hours postoperatively in 12 patients and 3- 11 days postoperatively in 3 patients. Treatment for ARDS comprised continuous hemodiafiltration (CHDF), high-dose glucocorticoid therapy or administration of a neutrophil elastase inhibitor (sivelestat). RESULTS: Four patients died 3-45 days after onset of ARDS (mortality rate, 26.6%). CHDF was performed in 12 patients, 8 patients received highdose glucocorticoid therapy and 11 patients received sivelestat. No differences in severity scores and clinical data were noted between survivors and non-survivors. PaO2/FiO2 ratio was significantly lower in non-survivors than in survivors from 5 days after starting treatment, whereas no difference was apparent at the onset of ARDS. CONCLUSIONS: Multimodal therapies for ARDS were effective. Longitudinal fluctuation in PaO2/ FiO2 ratio after starting treatment appears to offer a prognostic factor for ARDS.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Gastroenteropatias/cirurgia , Complicações Pós-Operatórias/terapia , Síndrome do Desconforto Respiratório/terapia , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Wilms tumor (WT) is the most common malignant kidney tumor in children. High blood pressure is seen in up to 55% of children with WT. However, hypertensive cardiomyopathy with congestive heart failure due to WT is remarkably rare, with only several cases reported worldwide. In this report, a pediatric case of WT with hypertension causing hypertensive cardiomyopathy and congestive heart failure is presented. An 8-month-old male child with abdominal distension was seen by his primary physician. He was referred to our hospital for further examination and treatment. Abdominal contrast-enhanced computed tomography demonstrated a weakly enhancing, large abdominal mass, which was larger than 12 cm. Two-dimensional transthoracic echocardiography showed a diffuse hypokinetic left ventricle. The patient was diagnosed with cardiomyopathy caused by hypertension. Open surgical resection of the mass was successfully performed. His postoperative course was uncomplicated, and the patient was successfully discharged. The plasma renin activity was maintained at a high level even after left nephrectomy, suggesting that the right kidney was likely the source of renin secretion. Mechanical compression of the right renal blood vessels by a greatly enlarged left kidney can cause right renal ischemia, which activates renin excretion. Nephrectomy can be an effective treatment for a WT patient with hypertension causing hypertensive cardiomyopathy, and then cardiac function will be improved within several weeks. We recommend routine echocardiography surveillance in patients with WT. This report can help pediatric surgeons become more familiar with cardiomyopathy caused by WT.
Assuntos
Cardiomiopatias/diagnóstico , Insuficiência Cardíaca/etiologia , Hipertensão/complicações , Renina/sangue , Tumor de Wilms/complicações , Cardiomiopatias/etiologia , Criança , Humanos , Lactente , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Masculino , Tumor de Wilms/sangue , Tumor de Wilms/cirurgiaRESUMO
Rubinstein-Taybi syndrome is an extremely rare autosomal dominant genetic disorder that occurs in 1/125,000 and is characterized by distinctive facial appearance, short stature, mild to severe mental retardation, and higher risk for cancer. In addition, variable organ anomalies had been reported. Paraovarian cyst causing torsion of the ipsilateral fallopian tube is less common, with an estimated incidence of 1/1,500,000, but it can adversely affect tubal function. It occurs mainly in women in the reproductive age and is very rare in prepubescent girls. Here, we described the successful treatment of an extremely rare case of paraovarian cyst causing torsion of the ipsilateral fallopian tube in a patient with Rubinstein-Taybi syndrome. A 14-year-old girl with Rubinstein-Taybi syndrome was referred to our hospital for abdominal pain. Her medical history was unremarkable, except for moderate hirsutism and keloid scar. Physical examination revealed tenderness in the lower abdominal midline. The preoperative diagnosis was torsion of a left ovarian cyst. An exploratory laparoscopy was performed because of acute abdominal pain and revealed a left fallopian tube that was twisted twice due to an ipsilateral paraovarian cyst. The huge paraovarian cyst required laparotomy cystectomy, and the left ovary was preserved. Her postoperative course was uncomplicated. Preoperative diagnosis of paraovarian cysts can be difficult. The moderate hirsutism seen in our patient suggested the presence of a large paraovarian cyst due to androgen receptor-mediated effects. Therefore, Rubinstein-Taybi syndrome patients with hirsutism should be screened and assessed by pediatric surgeons for the presence of paraovarian cysts.
Assuntos
Dor Abdominal/etiologia , Doenças das Tubas Uterinas/diagnóstico por imagem , Ovariectomia/métodos , Cisto Parovariano/cirurgia , Síndrome de Rubinstein-Taybi/complicações , Adolescente , Cistectomia , Doenças das Tubas Uterinas/cirurgia , Feminino , Hirsutismo , Humanos , Queloide , Laparoscopia , Laparotomia , Cisto Parovariano/diagnóstico por imagem , Síndrome de Rubinstein-Taybi/diagnóstico , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/etiologia , Anormalidade Torcional/cirurgia , Resultado do TratamentoRESUMO
The abilities to invade surrounding tissues and metastasize to distant organs are the most outstanding features that distinguish malignant from benign tumors. However, the mechanisms preventing the invasion and metastasis of benign tumor cells remain unclear. By using our own rat distant metastasis model, gene expression of cells in primary tumors was compared with that in metastasized tumors. Among many distinct gene expressions, we have focused on chloride intracellular channel protein 2 (CLIC2), an ion channel protein of as-yet unknown function, which was predominantly expressed in the primary tumors. We created CLIC2 overexpressing rat glioma cell line and utilized benign human meningioma cells with naturally high CLIC2 expression. CLIC2 was expressed at higher levels in benign human brain tumors than in their malignant counterparts. Moreover, its high expression was associated with prolonged survival in the rat metastasis and brain tumor models as well as with progression-free survival in patients with brain tumors. CLIC2 was also correlated with the decreased blood vessel permeability likely by increased contents of cell adhesion molecules. We found that CLIC2 was secreted extracellularly, and bound to matrix metalloproteinase (MMP) 14. Furthermore, CLIC2 prevented the localization of MMP14 in the plasma membrane, and inhibited its enzymatic activity. Indeed, overexpressing CLIC2 and recombinant CLIC2 protein effectively suppressed malignant cell invasion, whereas CLIC2 knockdown reversed these effects. Thus, CLIC2 suppress invasion and metastasis of benign tumors at least partly by inhibiting MMP14 activity.
Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Canais de Cloreto/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/etiologia , Permeabilidade Capilar/genética , Linhagem Celular Tumoral , Movimento Celular , Canais de Cloreto/genética , Ativação Enzimática , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Metaloproteinase 14 da Matriz/genética , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Ligação Proteica , Ratos , Microambiente TumoralRESUMO
We report a case of a 4-year-old girl with an ovarian steroid cell tumor, not otherwise specified (SCT-NOS). She was admitted to the hospital with progressing virilization and Cushing's syndrome, which included abnormality of the perineum, hirsutism, hypertrichosis, flushing of face, hoarseness, and weight gain. Blood testing showed a significantly increased testosterone level and slightly increased cortisol level. Computed tomography scan revealed an 8.0 × 5.0 × 5.0 cm tumor of the right ovary. The patient underwent right salpingo-oophorectomy, and pathological examination showed malignant potential. Three courses of bleomycin, etoposide, and cisplatin were administered as postoperative chemotherapy. After tumor resection, her testosterone decreased to undetectable levels. However, during the course of the treatment, the patient suffered from adrenal insufficiency resulting in the need for hydrocortisone replacement therapy. Although SCT-NOS in childhood are typically benign, pathological findings should be carefully observed for potential malignancy. In cases of cortisol-producing SCT-NOS, serum levels should be monitored, and hydrocortisone replacement therapy should be considered before resection.
RESUMO
Obstructive colitis (OC) is a nonspecific inflammatory condition that occurs at the proximal side of a completely or partially stenotic lesion typically caused by colorectal cancer. Impaired blood flow caused by these stenotic changes in the colon or rectum results in this condition. During surgery for sigmoid colon carcinoma with OC, complete surgical removal of the OC lesions is required. However, it is difficult to anticipate the range of OC before surgery. Diagnosing the potential ischemia during surgery would decrease the need for re-operation. This is the first report of HyperEye Medical System (HEMS) angiography for surgery of colon cancer with OC. We report a case of sigmoid colon carcinoma in which HEMS angiography was used and found to be useful for real-time detection of the OC lesion.
Assuntos
Angiografia/métodos , Colite/diagnóstico por imagem , Colite/cirurgia , Colo/irrigação sanguínea , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/cirurgia , Isquemia/diagnóstico , Margens de Excisão , Reto/irrigação sanguínea , Neoplasias do Colo Sigmoide/irrigação sanguínea , Neoplasias do Colo Sigmoide/cirurgia , Idoso , Colite/etiologia , Colite/fisiopatologia , Humanos , Verde de Indocianina , Obstrução Intestinal/etiologia , Obstrução Intestinal/fisiopatologia , Período Intraoperatório , Masculino , Neoplasias do Colo Sigmoide/complicações , Neoplasias do Colo Sigmoide/diagnóstico por imagemRESUMO
Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase ≥40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31+/CD45- endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis.
Assuntos
Canais de Cloreto/genética , Junções Íntimas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In this study, the first aza-Henry reaction of nitriles with nitromethane in a CuI/Cs2CO3/DBU system is described. The process was conveniently and directly used for the synthesis of ß-aminonitroalkenes 2a-x and tolerated aryl-, alkyl-, hetaryl-, alkenyl-, and alkynylnitriles. The resulting aminonitroalkenes 2 could be successfully transformed to the corresponding 2-nitroacetophenones, 2-amino-1-halonitroalkenes, 2-alkylaminonitroalkenes, or 3-nitropyridines. In the presence of H2O, the aza-Henry reaction turned the reaction path to the nitrile hydration to exclusively yield the amides 3a-s.