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PURPOSE: Pulmonary complications (PC) are a serious condition with a 20% mortality rate. However, few reports have examined risk factors for PC after colorectal surgery. This study investigated the frequency, characteristics, and risk factors for PC after colorectal cancer surgery. METHODS: Between January 2016 and December 2022, we retrospectively reviewed 3979 consecutive patients who underwent colorectal cancer surgery in seven participating hospitals. Patients were divided into patients who experienced PC (PC group, n = 54) and patients who did not (non-PC group, n = 3925). Clinical and pathological features were compared between groups. RESULTS: Fifty-four patients (1.5%) developed PC, of whom 2 patients (3.7%) died due to PC. Age was greater (80 years vs 71 years; p < 0.001), frequency of chronic obstructive pulmonary distress was greater (9.3% vs 3.2%; p = 0.029), performance status was poorer (p < 0.001), the proportion of underweight was higher (42.6% vs 13.4%, p < 0.001), frequency of open surgery was greater (24.1% vs 9.3%; p < 0.001), and blood loss was greater (40 mL vs 22 mL; p < 0.001) in the PC group. Multivariate analysis revealed male sex (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.176-3.986; p = 0.013), greater age (OR 3.180, 95%CI 1.798-5.624; p < 0.001), underweight (OR 3.961, 95%CI 2.210-7.100; p < 0.001), and poorer ASA-PS (OR 3.828, 95%CI 2.144-6.834; p < 0.001) as independent predictors of PC. CONCLUSION: Our study revealed male sex, greater age, underweight, and poorer ASA-PS as factors associated with development of PC, and suggested that pre- and postoperative rehabilitation and pneumonia control measures should be implemented for patients at high risk of PC.
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Neoplasias Colorretais , Complicações Pós-Operatórias , Humanos , Masculino , Fatores de Risco , Feminino , Idoso , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Japão/epidemiologia , Idoso de 80 Anos ou mais , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Pneumopatias/etiologia , Pneumopatias/epidemiologia , Estudos Retrospectivos , Cirurgia Colorretal/efeitos adversos , População do Leste AsiáticoRESUMO
PURPOSE: Positive pathologic lymph nodes in colorectal cancer represent an important prognostic indicator. Whether lymph node distribution or the number of metastatic nodes is more strongly associated with survival prediction remains controversial. METHODS: Among 3449 colorectal cancer surgeries performed at Nagasaki University Hospital and five affiliated institutions from April 2016 to March 2022, we investigated 604 patients who underwent laparoscopic radical resection and were diagnosed with pathological stage III cancer. Patients were divided into two groups according to whether they had central vessel metastasis (LND3 group, n=42) or not (LND1/2 group, n=562). After adjusting for background factors using propensity score matching, the LND3 group included 42 patients and the LND1/2 group included 40 patients. Patient background characteristics and prognosis were compared between these two groups. RESULTS: Before matching, frequencies of right-side colon cancer (64.3% vs 38.1%, p=0.001), multivisceral resection (11.9% vs 4.4%, p=0.039), clinical N2 status (40.5% vs 22.6%, p=0.032), and pathological N2 (73.8% vs 22.6%, p<0.001) were all greater, and the number of lymph nodes retrieved was higher (24 vs 19, p=0.042) in the LND3 group. After matching, no differences in any clinical factors were evident between groups. Five-year RFS (44.8% vs 77.1%, p=0.004) and OS (43.1% vs 83.2%, p<0.001) were worse in the LND3 group. Adjuvant chemotherapy improved RFS (adjuvant chemotherapy (+) vs adjuvant chemotherapy (-): 62.1% vs 27.7%, p=0.047) in the LND3 group. CONCLUSION: LND3-positive patients show poorer prognosis than LND1/2 patients and should be treated with an appropriate perioperative treatment strategy.
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Neoplasias Colorretais , Laparoscopia , Humanos , Prognóstico , Japão , Colectomia , Linfonodos , Neoplasias Colorretais/cirurgiaRESUMO
PURPOSE: Colorectal cancer is not common in patients under 40 years old, and its associations with clinical features and the prognosis remain uncertain. METHODS: Using a multicenter database, we retrospectively reviewed 3015 patients who underwent colorectal surgery between 2016 and 2021. Patients were divided by age into those < 40 years old (young; n = 52), 40-54 years old (middle-aged; n = 254) and > 54 years old (old; n = 2709). We then investigated age-related differences in clinicopathological features, perioperative outcomes and the prognosis. RESULTS: The proportion of young patients increased annually from 0.63% in 2016 to 2.10% in 2021. Female patients were more frequent, the performance status was better, tumors were larger, clinically node-positive and poorly differentiated adenocarcinomas were more frequent, postoperative complications were less frequent, and the hospital stay was shorter in young patients than in older patients. Young age was an independent predictor of a low risk of postoperative complications (odds ratio, 0.204; 95% confidence interval, 0.049-0.849; p = 0.028). With pathologically node-positive status, adjuvant chemotherapy was more frequent in young patients (100%) than in middle-aged (73.7%) or old (51.8%) patients (p < 0.001), and the 3-year relapse-free survival was better in the young group than in others. CONCLUSION: Despite higher rates of advanced tumors in younger patients, adequate adjuvant chemotherapy appears to improve the relapse-free survival.
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Neoplasias Colorretais , Recidiva Local de Neoplasia , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Adulto , Estudos Retrospectivos , Japão/epidemiologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Neoplasias Colorretais/patologia , Estadiamento de Neoplasias , Fatores EtáriosRESUMO
PURPOSE: The prognostic value of the lymphocyte-to-monocyte (LMR) ratio has been reported for various cancers, including colorectal cancer (CRC). The insertion of colonic stents is considered effective for patients with surgically indicated obstructive CRC, but their LMR can vary depending on factors such as inflammation associated with stent dilation and improvement of obstructive colitis. However, the usefulness of the LMR in patients with obstructive CRC and colonic stents and the optimal timing for its measurement remain unclear. We conducted this study to investigate the relationship between the pre-stent LMR and the mid-term prognosis of patients with obstructive CRC and stents as a bridge to surgery (BTS). METHODS: The subjects of this retrospective multicenter study were 175 patients with pathological stage 2 or 3 CRC. Patients were divided into a low pre-stent LMR group (n = 87) and a high pre-stent LMR group (n = 83). RESULTS: Only 3-year relapse-free survival differed significantly between the low and high pre-stent LMR groups (39.9% vs. 63.6%, respectively; p = 0.015). The pre-stent LMR represented a prognostic factor for relapse-free survival in multivariate analyses (hazard ratio 2.052, 95% confidence interval 1.242-3.389; p = 0.005), but not for overall survival. CONCLUSIONS: A low pre-stent LMR is a prognostic factor for postoperative recurrence in patients with obstructive CRC and a colonic stent as a BTS.
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PURPOSE: Several guidelines have recommended surgical resection for localized peritoneal metastases, but the prognosis remains poor. In addition, the efficacy of adjuvant chemotherapy (AC) after curative resection is under debate. The present study compared long-term outcomes between curative and non-curative resection and evaluated the effects of AC after curative resection. METHODS: Using a multicenter database, we retrospectively reviewed 123 colorectal cancer patients with peritoneal metastases between April 2016 and December 2021. Of these patients, 49 underwent curative resection, and 74 underwent non-curative resection. RESULTS: The frequency of broad metastases was lower in the curative resection group (8.2%) than in the non-curative resection group (43.2%, p < 0.001). Among all patients, 5-year overall survival rate was higher in the curative resection group (43.0%) than in the non-curative resection group (7.3%, p = 0.004). Among patients who underwent curative resection, 5-year overall survival rate was significantly higher in the AC group (48.2%) than in the non-AC group (38.1%, p = 0.037). Multivariate analysis of all patients revealed pathological N status and non-curative resection as independent predictors of overall survival. In patients who underwent curative resection, advanced age was an independent predictor of relapse-free survival, and AC was an independent predictor of overall survival. CONCLUSION: This multicenter study of colorectal cancer patients with peritoneal metastases revealed that prognosis was more favorable for curable cases than for non-curable cases. Prognosis was more favorable in the AC group than in the non-AC group after curative resection.
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Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Quimioterapia Adjuvante , Taxa de SobrevidaRESUMO
PURPOSE: Properly selecting patients for aggressive curative resection for pulmonary metastases (PMs) from colorectal cancer (CRC) is desirable. We purposed to clarify prognostic factors and risk factors for early recurrence after metachronous PM resection. METHODS: Clinical data of 151 patients who underwent R0 resection for metachronous PMs from CRC at two institutions between 2008 and 2021 were reviewed. RESULTS: Seventy-six patients (50.3%) were male, and the median age was 71 (42-91) years. The numbers of colon/rectal cancers were 76/75, with pStage I/II/III/IV/unknown in 15/34/86/13/3. The duration from primary surgery to PM was 19.7 (1.0-106.4) months. The follow-up period was 41.9 (0.3-156.2) months. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 75.1%, 53.7%, and 51.1%, and the 1-, 3-, and 5-year overall survival (OS) rates were 97.7%, 87.5%, and 68.2%. On multivariate analysis, lymph node metastasis of the primary lesion (HR 1.683, 95%CI 1.003-2.824, p = 0.049) was an independent predictor of poor RFS, and history of resection for extrapulmonary metastasis (e-PM) (HR 2.328, 95%CI 1.139-4.761, p = 0.021) was an independent predictor of poor OS. Patients who experienced early recurrence (< 6 months) after PM resection showed poorer OS than others (3-year OS 50.8% vs. 90.2%, p = 0.002). On multivariate analysis, e-PM was an independent predictor of early recurrence after PM resection (OR 3.989, 95%CI 1.002-15.885, p = 0.049). CONCLUSION: Since a history of e-PM was a predictor of early recurrence and poor OS after R0 resection for PM, surgical treatment of patients with a history of e-PM should be considered carefully.
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Neoplasias Colorretais , Neoplasias Pulmonares , Metastasectomia , Humanos , Masculino , Idoso , Feminino , Resultado do Tratamento , Neoplasias Colorretais/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/secundário , Taxa de Sobrevida , Recidiva Local de Neoplasia/cirurgia , Doença Crônica , Prognóstico , Estudos RetrospectivosRESUMO
Amelotin (AMTN) is an enamel protein that is localized in junctional epithelium (JE) of gingiva and suggested to be involved in the attachment between JE and tooth enamel. MicroRNA is a small non-coding RNA that regulates gene expression at post-transcriptional level by binding to the 3'-untranslated region (3'-UTR) of target mRNAs. In this study, we have analyzed the effects of miR-200b on the expression of AMTN in human gingival epithelial (Ca9-22) cells. Total RNAs and proteins were extracted from Ca9-22 cells transfected with miR-200b expression plasmid or miR-200b inhibitor and stimulated by TNF-α (10 ng/ml, 12 h). AMTN and inhibitor of kappa-B kinase beta (IKKß) mRNA and protein levels were measured by qPCR and Western blot. Human AMTN 3'-UTR that contains putative miR-200b target sites were cloned downstream of -353AMTN luciferase (LUC) plasmid. Ca9-22 cells were transfected with -353AMTN 3'-UTR LUC constructs and miR-200b expression plasmid, and LUC activities were measured with or without stimulation by TNF-α. TNF-α-induced AMTN mRNA levels were partially inhibited by miR-200b overexpression and enhanced by miR-200b inhibitor. TNF-α-induced IKKß mRNA and protein levels were almost completely inhibited by miR-200b. Transcriptional activities of -353AMTN 3'-UTR LUC constructs were induced by TNF-α and partially inhibited by miR-200b. IKKß inhibitor IMD0354 and NF-κB inhibitor triptolide decreased TNF-α-induced LUC activities. Furthermore, both inhibitors reduced AMTN mRNA levels in the presence or absence of TNF-α. These results suggest that miR-200b suppresses AMTN expression by targeting to AMTN and IKKß mRNAs in the human gingival epithelial cells.
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Proteínas do Esmalte Dentário , MicroRNAs , Proteínas do Esmalte Dentário/genética , Células Epiteliais , Gengiva , Humanos , MicroRNAs/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: The effectiveness of primary tumor resection (PTR) for asymptomatic stage IV colorectal cancer patients to continue prolonged and safe systemic chemotherapy has recently been re-evaluated. However, postoperative complications lead to a prolonged hospital stay and delay systemic treatment, which could result in a poor oncologic outcome. The objective of this study was to identify the risk factors for morbidity and delay of systemic chemotherapy in such patients. METHODS: Between April 2016 and March 2018, 115 consecutive colorectal cancer patients with distant metastasis who had no clinical symptoms and underwent PTR in all participating hospitals were retrospectively reviewed. The patients were divided into two groups according to the presence (CD ≥ 2, n = 23) or absence (CD < 2, n = 92) of postoperative complications. RESULTS: The proportion of combined resection of adjacent organs was significantly higher in the postoperative complication group (p = 0.014). Complications were significantly correlated with longer hospital stay (p < 0.001) and delay of first postoperative treatment (p = 0.005). Univariate and multivariate analyses showed that combined resection (odds ratio 4.593, p = 0.010) was the independent predictor for postoperative complications. Median survival time was 8.5 months. Postoperative complications were not associated with overall survival, but four patients (3.5%) could not receive systemic chemotherapy because of prolonged postoperative complications. CONCLUSIONS: Although PTR for asymptomatic stage IV CRC patients showed an acceptable prognosis, appropriate patient selection is needed to obtain its true benefit.
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Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Follicular dendritic cell-secreted protein (FDC-SP) is secreted protein expressed in follicular dendritic cells, periodontal ligament and junctional epithelium (JE). Its expression could be controlled during inflammatory process of gingiva; however, responsible mechanism for gingival overgrowth and involvement of FDC-SP in clinical condition is still unclear. We hypothesized that JE-specific genes are associated with the initiation of drug-induced gingival enlargement (DIGE) called gingival overgrowth, and investigated the changes of JE-specific gene's expression and their localization in overgrown gingiva from the patients. Immunohistochemical analysis revealed that the FDC-SP localization was spread in overgrown gingival tissues. FDC-SP mRNA levels in GE1 and Ca9-22 cells were increased by time-dependent nifedipine treatments, similar to other JE-specific genes, such as Amelotin (Amtn) and Lamininß3 subunit (Lamß3), whereas type 4 collagen (Col4) mRNA levels were decreased. Immunocytochemical analysis showed that FDC-SP, AMTN, and Lamß3 protein levels were increased in GE1 and Ca9-22 cells. Transient transfection analyses were performed using luciferase constructs including various lengths of human FDC-SP gene promoter, nifedipine increased luciferase activities of -345 and -948FDC-SP constructs. These results raise the possibility that the nifedipine-induced FDC-SP may be related to the mechanism responsible for gingival overgrowth does not occur at edentulous jaw ridges.
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Células Dendríticas Foliculares , Crescimento Excessivo da Gengiva , Inserção Epitelial , Gengiva , Humanos , NifedipinoRESUMO
Junctional epithelium (JE) demonstrates biological responses with the rapid turnover of gingival epithelial cells. The state occurs in inflammation of gingiva and wound healing after periodontal therapy. To understand the underlying mechanisms and to maintain homeostasis of JE, it is important to investigate roles of JE-specific genes. Amelotin (AMTN) is localized at JE and regulated by inflammatory cytokines and apoptotic factors that represent a critical role of AMTN in stabilizing the dentogingival attachment, which is an entrance of oral bacteria. In this study, we demonstrated that the AMTN gene expression was regulated by SNAI2 and transforming growth factor ß1 (TGFß1)-induced epithelial-mesenchymal transition (EMT) that occurs in wound healing and fibrosis during chronic inflammation. SNAI2 downregulated AMTN gene expression via SNAI2 bindings to E-boxes (E2 and E4) in the mouse AMTN gene promoter in EMT of gingival epithelial cells. Meanwhile, TGFß1-induced AMTN gene expression was attenuated by SNAI2 and TGFß1-induced SNAI2, without inhibition of the TGFß1-Smad3 signaling pathway. Moreover, SNAI2 small interfering RNA (siRNA) rescued SNAI2-induced downregulation of AMTN gene expression, and TGFß1-induced AMTN gene expression was potentiated by SNAI2 siRNA. Taken together, these data demonstrated that AMTN gene expression in the promotion of EMT was downregulated by SNAI2. The inhibitory effect of AMTN gene expression was an independent feedback on the TGFß1-Smad3 signaling pathway, suggesting that the mechanism can be engaged in maintaining homeostasis of gingival epithelial cells at JE and the wound healing phase.
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Proteínas do Esmalte Dentário/metabolismo , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Animais , Linhagem Celular , Proteínas do Esmalte Dentário/genética , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Gengiva/citologia , Camundongos , Fatores de Transcrição da Família Snail/genética , TransfecçãoRESUMO
Follicular dendritic cell-secreted protein (FDC-SP) is a secreted protein expressed in follicular dendritic cells, periodontal ligament and junctional epithelium. To elucidate the transcriptional regulation of the human FDC-SP gene by tumor necrosis factor-α (TNF-α), we conducted real-time PCR, Western blotting, transient transfection analyses with chimeric constructs of the FDC-SP gene promoter linked to a luciferase reporter gene, gel mobility shift and chromatin immunoprecipitation assays using Ca9-22 gingival epithelial cells. TNF-α (10 ng/ml) induced FDC-SP mRNA and protein levels at 3 hr and reached maximum at 12 hr. In transient transfection assays, TNF-α (12 hr) increased the LUC activities of constructs between -116FDCSP and -948FDCSP including the human FDC-SP gene promoter. Transcriptional stimulations by TNF-α were partially inhibited in the -345FDCSP constructs that included 3-bp mutations in the YY1, GATA, CCAAT enhancer-binding protein 2 (C/EBP2) and C/EBP3. Transcriptional activities induced by TNF-α were inhibited by tyrosine kinase, MEK1/2 and phosphoinositide 3-kinase inhibitors. The results of ChIP assays showed that YY1, GATA and C/EBPß transcription factors interacted with the YY1, GATA, C/EBP2 and C/EBP3 elements that were increased by TNF-α. These studies show that TNF-α stimulates human FDC-SP gene transcription by targeting YY1, GATA, C/EBP2 and C/EBP3 in the FDC-SP gene promoter.
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Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Gengiva/metabolismo , Proteínas/genética , Transcrição Gênica , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Células Cultivadas , Células Epiteliais/citologia , Fatores de Transcrição GATA/genética , Fatores de Transcrição GATA/metabolismo , Gengiva/citologia , Humanos , Regiões Promotoras Genéticas , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismoRESUMO
OBJECTIVE: Amelotin (AMTN) is an enamel protein that is localized in the basal lamina of ameloblasts in their maturation stage and the internal basal lamina of junctional epithelium (JE) and it is suggested that AMTN could be involved in the dentogingival attachment. To elucidate the transcriptional regulation of human AMTN gene in inflamed gingiva, we have analyzed the effect of tumor necrosis factor-α (TNF-α) on the expression of AMTN gene in Ca9-22 and Sa3 human gingival epithelial cells. MATERIALS AND METHODS: Total RNAs were extracted from Ca9-22 and Sa3 cells after stimulation by TNF-α (10 ng/ml). AMTN mRNA and protein levels were measured by real-time PCR and Western blotting. Transient transfection analyses were completed using the various lengths of human AMTN gene promoter constructs with or without TNF-α. Gel mobility shift and chromatin immunoprecipitation assays were performed to investigate the transcription factors bindings to the human AMTN gene promoter by TNF-α. RESULTS: TNF-α (10 ng/ml) increased AMTN mRNA and protein levels after 12 h. TNF-α induced luciferase activities of human AMTN gene promoter constructs (- 211AMTN, - 353AMTN, and - 501AMTN). TNF-α-induced luciferase activities were partially inhibited in the mutation - 353AMTN constructs that included 3-bp mutations in CCAAT enhancer-binding protein 1 (C/EBP1), C/EBP2 and Ying Yang 1 (YY1) elements. Transcriptional activities induced by TNF-α were inhibited by protein kinase A, Src-tyrosine kinase, MEK1/2, p38 kinase, NF-κB, and PI3-kinase inhibitors. Gel shift assays showed that TNF-α increased nuclear proteins binding to two types of C/EBP elements (C/EBP1 and C/EBP2) and YY1 element. The results of the chromatin immunoprecipitation assays showed that C/EBPß binding to C/EBP1 and C/EBP2, and YY1 binding to YY1 were increased by TNF-α. CONCLUSIONS: These findings demonstrated that TNF-α stimulates AMTN gene transcription in human gingival epithelial cells via C/EBP1, C/EBP2, and YY1 elements in the human AMTN gene promoter.
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Proteínas do Esmalte Dentário/genética , Gengiva/metabolismo , Transcrição Gênica , Fator de Necrose Tumoral alfa/fisiologia , Linhagem Celular Tumoral , Proteínas do Esmalte Dentário/metabolismo , Células Epiteliais/metabolismo , Humanos , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Bone sialoprotein (BSP) is a glycoprotein associated with mineralized tissues. In this study, we investigated the regulation of Bsp transcription by calcium hydroxide [Ca(OH)2 ] in rat osteosarcoma-derived osteoblast-like ROS 17/2.8 cells and stromal bone marrow cells. Application of Ca(OH)2 (0.4 mM) increased the levels of runt-related transcription factor 2 (Runx2) and BspmRNAs at 3 and 6 h and the level of BSP protein at 12 h. Transient transfection analyses were performed using chimeric constructs encompassing different regions of the rat Bsp gene promoter ligated to a luciferase reporter gene. It was found that Ca(OH)2 increased the luciferase activities of the pLUC3 and pLUC4 constructs. Introduction of 2-bp mutations to the luciferase construct showed that the effects of Ca(OH)2 were mediated by cAMP response-element (CRE) and fibroblast growth factor 2 (FGF2) response element (FRE). Luciferase activities induced by Ca(OH)2 were blocked by protein kinase C (PKC), protein kinase A (PKA), phosphoinositide-3-kinase (PI3-K), and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors and by calcium-sensing receptor (CASR) antagonists. Gel-shift analyses showed that Ca(OH)2 increased binding of nuclear protein to CRE and FRE. Dexamethasone-induced mineralization in stromal bone marrow cells was abrogated by CASR antagonists. These studies demonstrate that Ca(OH)2 regulates Bsp transcription via the CASR by targeting CRE and FRE in the rat Bsp gene promoter.
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Hidróxido de Cálcio/farmacologia , Regulação da Expressão Gênica , Sialoproteína de Ligação à Integrina/genética , Receptores de Detecção de Cálcio/metabolismo , Transcrição Gênica , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Sialoproteína de Ligação à Integrina/metabolismo , RNA Mensageiro/metabolismo , Ratos , Receptores de Detecção de Cálcio/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Células Tumorais CultivadasRESUMO
The purpose of this study is to elucidate the localization of amelotin (AMTN), odontogenic ameloblast-associated protein (ODAM) and follicular dendritic cell-secreted protein (FDC-SP) at the junctional epithelium (JE) in Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans infected mice and inflamed and non-inflamed human gingiva. We performed immunostaining to determine the localization and expression pattern of AMTN, ODAM and FDC-SP. AMTN, ODAM and FDC-SP in A. actinomycetemcomitans infected mice did not change dramatically compared with non-infected mice. AMTN and FDC-SP expressions were observed stronger in P. gingivalis infected mice at early stage. However, at the following stage, the coronal part of the AMTN expression disappeared from the JE, and FDC-SP expression decreased due to severe inflammation by P. gingivalis. ODAM expressed internal and external basal lamina, and the expression increased not only at early stage but also at the following stage in the inflammatory JE induced by P. gingivalis. In the human gingival tissues, AMTN was detected at the surface of the sulcular epithelium and JE in the non-inflamed and inflamed gingiva, and the localization did not change the process of inflammation. ODAM and FDC-SP were more widely detected at the sulcular epithelium and JE in the non-inflamed gingiva. In the inflamed gingiva, localization of ODAM and FDC-SP was spread into the gingival epithelium, compared to AMTN. These studies demonstrated that the expression pattern of AMTN, ODAM and FDC-SP at the JE were changed during inflammation process and these three proteins might play an important role in the resistance to inflammation.
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Infecções por Bacteroidaceae/metabolismo , Proteínas do Esmalte Dentário/metabolismo , Inserção Epitelial/metabolismo , Gengiva/metabolismo , Infecções por Pasteurellaceae/metabolismo , Periodontite/metabolismo , Proteínas/metabolismo , Aggregatibacter actinomycetemcomitans , Animais , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Porphyromonas gingivalisRESUMO
Amelotin (AMTN) is expressed and secreted by ameloblasts in the maturation stage of amelogenesis and persist with low levels in the junctional epithelium (JE) of erupted teeth. The purpose of this study is to investigate the transcriptional regulation of the AMTN gene by transforming growth factor beta1 (TGFß1) in gingival epithelial (GE1) cells in the apoptosis phase. Apoptosis was evaluated by the fragmentation of chromosomal DNA and TUNEL staining. A real-time PCR was carried out to examine the AMTN mRNA levels induced by TGFß1 and Smad3 overexpression. Transient transfection analyses were completed using the various lengths of mouse AMTN gene promoter constructs with or without TGFß1. Chromatin immunoprecipitation (ChIP) assays were performed to investigate the Smad3 bindings to the AMTN gene promoter by TGFß1. TGFß1-induced apoptosis in GE1 cells were detected at 24 and 48 h by DNA fragmentation and TUNEL staining. AMTN mRNA levels increased at 6 h and reached maximum at 24 h in GE1 cells. Luciferase activities of the mouse AMTN gene promoter constructs were induced by TGFß1. The results of the ChIP assays showed that there was an increase in Smad3 binding to Smad-binding element (SBE)#1 and SBE#2 after stimulation by TGFß1. Immunohistochemical localization of AMTN was detected in the JE, and the AMTN protein levels in Smad3-deficient mice were decreased compared with wild-type mice. AMTN mRNA levels were induced at the initiation of apoptosis by TGFß1, which mediated through the Smad3 bindings to SBEs in the mouse AMTN gene promoter.
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Apoptose , Proteínas do Esmalte Dentário/genética , Células Epiteliais/metabolismo , Gengiva/citologia , Fator de Crescimento Transformador beta1/genética , Animais , Proteínas do Esmalte Dentário/metabolismo , Células Epiteliais/citologia , Gengiva/metabolismo , Camundongos , Regiões Promotoras Genéticas , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Pancreatic and duodenal-related complications after right colectomy carry a higher risk of mortality. CASE PRESENTATION: A 64-year-old woman underwent laparoscopic right colectomy for a laterally spreading tumor in the cecum. On postoperative day 10, she experienced sudden hematemesis. Contrast-enhanced computed tomography (CT) of the abdomen showed a large amount of hemorrhage in the stomach, but no obvious extravasation. In addition, free air was observed near the duodenal bulb. Despite blood transfusion, vital signs remained unstable and emergency surgery was performed. The abdomen was opened through midline incisions in the upper and lower abdomen. A fragile wall and perforation were observed at the border of the left side of the duodenal bulb and pancreas, with active bleeding observed from inside. As visualization of the bleeding point proved difficult, the duodenum was divided circumferentially to confirm the bleeding point and hemostasis was performed using 4-0 PDS. The left posterior wall of the duodenum was missing, exposing the pancreatic head. For reconstruction, the jejunum was elevated via the posterior colonic route and the duodenal segment and elevated jejunum were anastomosed in an end-to-side manner. Subsequently, gastrojejunal and Brown anastomoses were added. Drains were placed before and after the duodenojejunal anastomosis. Postoperative vital signs were stable and the patient was extubated on postoperative day 1. Follow-up contrast-enhanced CT of the abdomen showed no active bleeding, and the patient was discharged home on postoperative day 21. As of 6 months postoperatively, the course of recovery has been uneventful. CONCLUSIONS: We encountered a case of pancreaticoduodenal artery hemorrhage after laparoscopic right colectomy. Bleeding at this site can prove fatal, so treatment plans should be formulated according to the urgency of the situation.
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BACKGROUND: Intestinal Behçet's disease (BD) is often associated with ulceration that requires surgery, including perforation and abscess formation. However, no consensus has been reached on the optimal extent of resection or treatment strategy. This study reviewed four cases of intestinal or suspected intestinal BD. CASE PRESENTATIONS: In Case 1, a 74-year-old woman diagnosed with BD 2 years earlier was treated with anti-tumor necrosis factor α antibody (Infliximab) and steroids. She had oral and pubic ulcers. After close investigation of abdominal pain, perforation of the gastrointestinal tract was suspected and surgery was performed. Multiple perforating ulcers and abscesses were found in the distal ileum, and the small intestine was resected. Postoperatively, the patient was treated with an increased steroid dose and symptoms have remained stable. Case 2 involved a 69-year-old woman with oral and pubic ulcers, ocular ulcer, and skin lesions. She experienced sudden onset of abdominal pain during treatment for lymphoma. She showed multiple perforating ulcers throughout the ileum and underwent resection of the small intestine and ileostomy. Upper abdominal pain appeared during postoperative treatment for high-output syndrome. The patient underwent omentoplasty after perforation of the upper gastrointestinal tract was diagnosed. Postoperatively, anti-interleukin-1 beta antibodies (canakinumab) was administered to control the disease. Case 3 involved an 81-year-old, previously healthy woman. She presented to her previous physician with complaints of pubic ulcer, hemorrhage and abdominal pain. Colonoscopy showed multiple ulcers throughout the entire colon. Steroid therapy was started, but bleeding proved difficult to control and total proctocolectomy was performed. Histopathology revealed multiple perforating ulcers and BD was diagnosed. Postoperatively, the patient remains under steroid control. Case 4 involved a 43-year-old man with abdominal pain who showed abscess formation in the ileocecal region. After excision of the ileocecal area, multiple ulcers were diagnosed. Two years later, abdominal pain recurred and free air was found in the abdomen on close imaging. Emergency anastomotic resection was performed due to ulceration and perforation of the anastomosis. CONCLUSIONS: Intestinal BD may flare up after surgical treatment and require multiple surgeries. Introducing pharmacotherapy as soon as possible after surgical treatment is important to control the disease.
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INTRODUCTION: Thirty-day reoperation rate reflects short-term surgical outcomes following surgery. Laparoscopic surgery for colorectal cancer reportedly has positive effects on postoperative complications. This retrospective study investigated risk factors for 30-day reoperation rate among patients after laparoscopic colorectal cancer surgery using a multicenter database. METHODS: Participants comprised 3037 patients who had undergone laparoscopic resection of colorectal cancer between April 2016 and December 2022 at the Nagasaki University and six affiliated centers, classified into those who had undergone reoperation within 30 days after surgery (RO group; n = 88) and those who had not (NRO group; n = 2949). Clinicopathological characteristics were compared between groups. RESULTS: In the RO group, anastomotic leakage occurred in 57 patients (64.8%), intestinal obstruction in 12 (13.6%), and intraabdominal abscess in 5 (5.7%). Female patients were more frequent, preoperative treatment less frequent, body mass index (BMI) lower, operation time longer, blood loss greater, and hospital stay longer in the RO group (p < .05 each). Multivariate analysis revealed BMI (odds ratio, 0.415; 95% confidence interval, 0.218-0.787; p = .021) and poor performance status (odds ratio, 1.966; 95% confidence interval, 1.106-3.492; p = .021) as independent predictors of reoperation. CONCLUSION: Perioperative measures are warranted for patients with low BMI and poor performance status undergoing laparoscopic colorectal surgery.
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Neoplasias Colorretais , Laparoscopia , Feminino , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Japão/epidemiologia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , MasculinoRESUMO
BACKGROUND/AIM: Colonic stents have been inserted as a bridge to surgery in patients with resectable colorectal cancer, allowing bowel decompression for systemic assessment and better preparation to avoid stoma construction. However, reports of short- and long-term prognoses for elderly patients remain limited. PATIENTS AND METHODS: This retrospective study reviewed 175 consecutive patients who underwent colonic stent insertion for bowel obstruction followed by curative colectomy. Patients were divided into those >80 years old (Old, n=49) and those <80 years old (Young, n=126). After propensity score matching, 41 patients in each group matched. RESULTS: Before matching, performance status was poorer (p<0.001), postoperative complication rate was higher (p=0.009), adjuvant chemotherapy rate was lower (p<0.001), and hospital stay was longer (p<0.001) in the Old group. After matching, adjuvant chemotherapy rate was lower (9.8% vs. 39.0%; p=0.003) and hospital stay was longer (14 vs. 12 days; p=0.029) in the Old group. Five-year relapse-free survival (42.9% vs. 68.8%; p=0.200), overall survival (66.3% vs. 87.7%; p=0.081), and cancer-specific survival (68.2% vs. 87.7%; p=0.129) rates were comparable between groups. CONCLUSION: Colorectal resection after colonic stent insertion is useful for elderly patients, with potential to reduce postoperative complication rates and achieve good long-term results with appropriate case selection.
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Neoplasias Colorretais , Obstrução Intestinal , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Recidiva Local de Neoplasia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicações , Stents/efeitos adversos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
INTRODUCTION: The impact of institutional volume on postoperative outcomes after laparoscopic colectomy is still being debated. This study aimed to investigate whether differences in postoperative outcomes of laparoscopic colon resection exist between high- and low-volume centers. METHODS: Data were reviewed for 1360 patients who underwent laparoscopic colectomy for colon cancer between 2016 and 2022. Patients were divided according to whether they were treated at a high-volume center (≥100 colorectal surgeries annually; n = 947) or a low-volume center (<100 colorectal surgeries annually; n = 413). Propensity score matching was applied to balance covariates and minimize selection biases that could affect outcomes. Finally, 406 patients from each group were matched. RESULTS: After matching, patients from high-volume centers showed a higher number of retrieved lymph nodes (19 vs. 17, p < .001) and more frequent involvement of expert surgeons (98.3% vs. 88.4%, p < .001). Postoperative complication rates were similar between groups (p = .488). No significant differences between high- and low-volume centers were seen in relapse-free survival (88.8% each, p = .716) or overall survival (85.7% vs. 82.8%, p = .480). CONCLUSION: The present study suggests that in appropriately educated organizations, relatively safe procedures and good prognosis may be obtained for laparoscopic colectomy cases, regardless of institutional volume.