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BACKGROUND AND PURPOSE: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. METHODS: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. RESULTS: The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). CONCLUSION: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy.
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Neoplasias Gástricas , Humanos , Idoso , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Prognóstico , Músculo Esquelético/patologia , Quimioterapia Adjuvante , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Gastrectomia/efeitos adversosRESUMO
PURPOSE: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.
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Neoplasias Gástricas , Humanos , Prognóstico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico , Caquexia/etiologia , Caquexia/tratamento farmacológico , Estudos Retrospectivos , Fluoruracila/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
PURPOSE: This study was performed to investigate the predictive value of the perioperative D-dimer concentration for the development of postoperative deep vein thrombosis (DVT) after hepatobiliary-pancreatic (HBP) surgery. METHODS: The subjects of this retrospective study were 178 patients who underwent HBP surgery in our hospital between January, 2017 and December, 2021. The D-dimer concentration was measured preoperatively and on postoperative days (POD) 1, 3, and 5. Postoperative DVT was diagnosed based on compression ultrasonography in both lower limbs on POD 6 or 7. RESULTS: Postoperative DVT developed in 21 (11.8%) of the 178 patients. The D-dimer concentration was significantly higher in the patients with than in those without postoperative DVT before surgery and on PODs 1, 3, and 5. The highest area under the curve of the D-dimer concentration for predicting DVT was 0.762 on POD 3. Multivariate analysis revealed that the D-dimer concentration on POD 3 was an independent predictive risk factor for postoperative DVT, along with the preoperative estimated glomerular filtration rate. Preoperative albumin and D-dimer concentrations were also identified as independent predictive factors of an increase in D-dimer concentration on POD 3. CONCLUSIONS: The D-dimer concentration on POD 3 is a useful predictor of DVT after HBP surgery.
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Trombose Venosa , Humanos , Estudos Retrospectivos , Valor Preditivo dos Testes , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologiaRESUMO
PURPOSE: Perioperative surgical stress and systemic inflammation resulting from complex interactions between cancer and the host play an important role in cancer progression. This retrospective study compared the prognostic impact of various perioperative cumulative inflammation- and nutrition-based markers in patients with gastric cancer (GC). METHODS: This study included 301 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery. Perioperative cumulative markers were calculated using the newly developed trapezoidal area method. RESULTS: The cumulative prognostic nutritional index (cum-PNI) had the highest area under the receiver operating characteristic (ROC) curve for predicting the overall survival (OS) as well as the relapse-free survival (RFS). The cum-PNI was significantly correlated with tumor-related factors, including tumor size, depth of invasion, lymph node metastasis, lymphatic involvement, vascular involvement, and TNM stage classification. The cum-PNI was also significantly correlated with surgical factors, including surgical approach, gastrectomy, lymphadenectomy, intraoperative blood loss, and postoperative complications. Furthermore, the OS and RFS were poorer in patients with a low cum-PNI (< 236.3) than in those with a high cum-PNI (> 236.3). A multivariate analysis indicated that a low cum-PNI was an independent prognostic indicator in patients with GC. CONCLUSIONS: The cum-PNI might be useful for predicting the prognosis and guiding the perioperative management of patients with GC.
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Avaliação Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Prognóstico , Japão/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Estado Nutricional , Inflamação , Gastrectomia/efeitos adversosRESUMO
BACKGROUND: Ferroptosis suppressor protein 1 and glutathione peroxidase 4 have been identified as key molecules in two independent pathways associated with ferroptosis inhibition. This study investigated the prognostic significance and clinical associations of FSP1 and GPX4 expression in esophageal squamous cell carcinoma (ESCC) and assessed the therapeutic potential of regulating these molecules in ESCC cells. METHODS: Immunohistochemical analysis was performed on surgical specimens of 97 patients with ESCC for FSP1 and GPX4 expression. To identify the change in ESCC cell viability, FSP1 and GPX4 inhibitors were administered to three cell lines. In addition, ferroptosis as the cause of reduced cell viability by FSP1 and GPX4 inhibition was confirmed. RESULTS: Prognosis was significantly worse for patients in the group positive for both FSP1 and GPX4 compared with the other groups (p < 0.001). In multivariate analysis, positivity for both FSP1 and GPX4 was an independent poor prognostic factor (p = 0.002). The combination of FSP1 and GPX4 inhibitors induced cell death more potently than each inhibitor did alone. Furthermore, the ferroptosis inhibitor markedly canceled this cell death. CONCLUSIONS: Overexpression of FSP1 and GPX4 is a poor prognostic factor for patients with ESCC. Simultaneous suppression of both FSP1 and GPX4 caused potent cell death, which was markedly abrogated by ferroptosis inhibitors. These findings indicate that simultaneous regulation of FSP1 and GPX4 may be a new therapeutic target in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , PrognósticoRESUMO
BACKGROUND: The systemic inflammatory response resulting from the complex interactions between cancer and the host plays an important role in cancer development. Recently, the lymphocyte-C-reactive protein ratio (LCR), which is a hematological and biochemical marker that reflects the systemic inflammatory response and nutritional status, has been reported to be associated with poor survival. Similar results were observed in patients with certain cancer types. However, these studies focused on the preoperative LCR, and thus far, no studies have reported the relationship between postoperative LCR and prognosis in patients with gastric cancer (GC). METHODS: This study enrolled 455 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery at our institution between 2005 and 2018. The relationship between both the preoperative and postoperative LCR and the prognosis of patients with GC was retrospectively investigated. RESULTS: Preoperative LCR showed significant correlations with tumor-related factors, such as tumor size, depth of invasion, and lymph node metastasis. By contrast, no correlation was observed between postoperative LCR and tumor-related factors. The 5 year survival rate was significantly worse in patients with low preoperative LCR than in those with high preoperative LCR (65.4% vs. 83.9%, p < 0.0001). Similarly, the 5 year survival rate was also significantly worse in patients with low postoperative LCR than in those with high postoperative LCR (67.0% vs. 84.1%, p < 0.0001). Furthermore, combination analysis of the pre- and postoperative LCR revealed that the prognosis of patients with both low pre- and postoperative LCR was worse in patients with GC (5 year survival rate was 52.0%). A multivariate analysis indicated that a low pre- and postoperative LCR and age and lymph node metastasis were independent prognostic indicators. CONCLUSIONS: The combination of preoperative and postoperative LCR appears to be useful in predicting the prognosis of patients with GC.
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Neoplasias Gástricas , Proteína C-Reativa/análise , Humanos , Metástase Linfática , Linfócitos/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Síndrome de Resposta Inflamatória SistêmicaRESUMO
BACKGROUND: Thoracoscopic esophagectomy has been extensively used worldwide as a curative surgery for patients with esophageal cancer; however, complications such as anastomotic leakage and stenosis remain a major concern. Therefore, the objective of this study was to evaluate the efficacy of circular stapling anastomosis with indocyanine green (ICG) fluorescence imaging, which was standardized for cervical esophagogastric anastomosis after thoracoscopic esophagectomy. METHODS: Altogether, 121 patients with esophageal cancer who underwent thoracoscopic esophagectomy with radical lymph node dissection and cervical esophagogastric anastomosis from November 2009 to December 2020 at Tottori University Hospital were enrolled in this study. Patients who underwent surgery before the anastomotic method was standardized were included in the classical group (n = 82) and patients who underwent surgery after the anastomotic method was standardized were included in the ICG circular group (n = 39). The short-term postoperative outcomes, including anastomotic complications, were compared between the two groups using propensity-matched analysis and the risk factors for anastomotic leakage were evaluated using logistic regression analyses. RESULTS: Of the 121 patients, 33 were included in each group after propensity score matching. The clinicopathological characteristics of patients did not differ between the two groups after propensity score matching. In terms of perioperative outcomes, a significantly higher proportion of patients who underwent surgery using the laparoscopic approach (P < 0.001) and narrow gastric tube (P = 0.003), as well as those who had a lower volume of blood loss (P = 0.009) in the ICG circular group were observed after matching. Moreover, the ICG circular group had a significantly lower incidence of anastomotic leakage (39% vs. 9%, P = 0.004) and anastomotic stenosis (46% vs. 21%, P = 0.037) and a shorter postoperative hospital stay (30 vs. 20 days, P < 0.001) than the classical group. According to the multivariate analysis, the anastomotic method was an independent risk factor for anastomotic leakage after thoracoscopic esophagectomy (P = 0.013). CONCLUSIONS: Circular stapling anastomosis with ICG fluorescence imaging is effective in reducing complications such as anastomotic leakage and stenosis.
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Neoplasias Esofágicas , Esofagectomia , Anastomose Cirúrgica/métodos , Fístula Anastomótica/etiologia , Constrição Patológica/cirurgia , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Humanos , Verde de Indocianina , Imagem Óptica , Pontuação de PropensãoRESUMO
BACKGROUND: Due to its tumor-specific metabolic pathway characteristics, 5-aminolevulinic acid (5-ALA) is a natural amino acid widely used in cancer treatment. The current study, demonstrated that 5-ALA induced ferroptosis via glutathione peroxidase 4 (GPX4) and heme oxygenase 1 (HMOX1) and had an antitumor effect in esophageal squamous cell carcinoma (ESCC). METHODS: Expression of GPX4 and HMOX1 in pathologic specimens of 97 ESCC patients was examined, and prognostic analyses were performed. Real-time polymerase chain reaction (RT-PCR), RNA microarray, and Western blotting analyses were used to evaluate the role of 5-ALA in ferroptosis in vitro. In addition, this study used ferrostatin-1, a ferroptosis inhibitor, and a lipid peroxidation reagent against cell lines treated with 5-ALA. Finally, the role of 5-ALA was confirmed by its effect on an ESCC subcutaneous xenograft mouse model. RESULTS: The study showed that upregulation of GPX4 and downregulation of HMOX1 were poor prognostic factors in ESCC. In an RNA microarray analysis of KYSE30, ferroptosis was one of the most frequently induced pathways, with GPX4 suppressed and HMOX1 overexpressed by 5-ALA treatment. These findings were verified by RT-PCR and Western blotting. Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. In vivo, 5-ALA suppressed GPX4 and overexpressed HMOX1 in tumor tissues and led to a reduction in tumor size. CONCLUSIONS: Modulation of GPX4 and HMOX1 by 5-ALA induced ferroptosis in ESCC. Thus, 5-ALA could be a promising new therapeutic agent for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , Ácido Aminolevulínico/farmacologia , Animais , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Camundongos , Fosfolipídeo Hidroperóxido Glutationa PeroxidaseRESUMO
BACKGROUND: The mortality rate of patients with unresectable gastric cancer (UGC) has decreased with the development of chemotherapies and surgical techniques. However, the survival rate remains low. We retrospectively examined the prognostic significance of the pretreatment skeletal muscle mass index (SMI) and nutritional and inflammatory factors in patients with UGC. METHODS: This study included 83 patients diagnosed with UGC at Tottori University Hospital who received palliative chemotherapy based on 5-fluorouracil. Pretreatment computed tomography (CT) measured overall skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra (L3). We focused on the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and platelet-to-lymphocyte ratio (PLR) as nutritional and inflammatory factors. RESULTS: Receiver operating characteristic curve analysis was performed for median survival time (MST) after palliative chemotherapy. SMIs for males and females (43.9 cm2/m2 and 34.7 cm2/m2, respectively) were the cutoff values, and patients were divided into high (SMIHigh; n = 41) and low SMI groups (SMILow; n = 42). Body mass index (BMI) was significantly higher in patients in the SMIHigh group than in the SMILow group (p < 0.001). The number of patients who received third-line chemotherapy was significantly higher in the SMIHigh group than in the SMILow group (p = 0.037). The MST was significantly higher in the SMIHigh group than in the SMILow group (17.3 vs. 13.8 months; p = 0.008). The incidence of grade 3 or 4 side effects was significantly higher in patients with SMILow UGC (p = 0.028). NLR was significantly higher in patients with SMILow than it was in those with SMIHigh. (p = 0.047). In the univariate analysis, performance status, SMI, histological type, lines of chemotherapy, and NLR were prognostic indicators. The multivariate analysis identified SMI (p = 0.037), NLR (p = 0.002), and lines of chemotherapy (p < 0.001) as independent prognostic factors. CONCLUSIONS: The SMILow group had significantly more grade 3 or 4 side effects, were related to high NLR, and had a significantly worse prognosis than the SMIHigh group. TRIAL REGISTRATION: Retrospectively registerd.
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Antimetabólitos Antineoplásicos/uso terapêutico , Fluoruracila/uso terapêutico , Músculo Esquelético/anatomia & histologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Plaquetas/citologia , Índice de Massa Corporal , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Fluoruracila/efeitos adversos , Gastrectomia , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Neutrófilos/citologia , Fenômenos Fisiológicos da Nutrição , Cuidados Paliativos , Prognóstico , Curva ROC , Estudos Retrospectivos , Sarcopenia/complicações , Albumina Sérica/análise , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: We retrospectively examined the relationship among skeletal muscle mass index (SMI), prognosis, and chemotherapy side effects in patients with recurrent gastric cancer (RGC). METHODS: Sixty-seven patients who developed recurrence after undergoing curative gastrectomy for gastric cancer at Tottori University Hospital and received palliative chemotherapy were included in this study. Pretreatment computed tomography was performed to measure the skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra. We focused on haematologic toxicity (neutropenia, thrombocytopenia, and anaemia), febrile neutropenia, and gastrointestinal toxicity (diarrhoea, vomiting, and stomatitis) as the side effects of chemotherapy. RESULTS: Median SMIs for males and females (43.9 and 34.7 cm2/m2, respectively) were used as cutoff values. The patients were classified into high (SMIHigh; n = 34) and low SMI groups (SMILow; n = 33). The SMILow group included more patients treated with monotherapy (P = 0.016) compared with the SMIHigh group, had a significantly lower number of chemotherapy lines (P = 0.049), and had a significantly higher incidence of grade 3 or 4 side effects (P = 0.010). The median survival rate was significantly higher in the SMIHigh group (17.8 vs 15.8 months; P = 0.034). In the univariate analysis, body mass index, SMI, histological type, and prognostic nutritional index were identified as prognostic indicators. The multivariate analysis identified SMI (P = 0.037) and histological type (P = 0.028) as independent prognostic factors. CONCLUSION: The incidence of grade 3 or 4 side effects was significantly higher in patients with SMILow RGC. SMI was a useful prognostic marker of RGC.
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Sarcopenia , Neoplasias Gástricas , Estudos Transversais , Feminino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
A 56-years old man was diagnosed with cervical esophageal cancer with lymph node metastasis. After definitive chemoradiotherapy as the first-line therapy, complete response(CR)was obtained. One year and 3 months after the therapy, lymph node dissection and postoperative chemotherapy was performed for the lymph node metastases of the left neck and axillary lymph node. After 3 years and 10 months from the first-line therapy, follow-up CT revealed left axillary lymph node swelling and diagnosed with lymph node recurrence. Chemoradiotherapy was performed for the recurrence of the lymph node and CR was achieved for the lymph node. However, left axillary lymph node swelling were detected again 6 years after the first-line therapy. After 6 months of chemotherapy with S-1, CR was achieved for the lymph node again. He is now alive without recurrence for 10 years after the first-line therapy.
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Neoplasias Esofágicas , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Masculino , Pessoa de Meia-IdadeRESUMO
A suture placed next to a dissected liver section during the initial hepatectomy may become an unlikely intrahepatic foreign body granuloma. In this report, we describe a case where a silk suture in the liver section plane placed during initial hepatectomy for synchronous colon cancer metastasis became an intrahepatic foreign body granuloma that exhibited fluorodeoxyglucose (FDG) accumulation on positron emission tomography/computed tomography (PET/CT). The granuloma was resected as the second metachronous liver metastatic lesion. A 73-year-old female was referred for a planned second hepatectomy. She had undergone colectomy and hepatectomy for advanced cancer of the ascending colon and synchronous liver metastasis approximately two years ago. However, two possible liver metastases with FDG accumulation were identified in hepatic segments IV and V after one year and nine months after the initial resection. A second hepatectomy was planned after administering systemic chemotherapy. She underwent a left lobectomy with a middle hepatic vein and partial segment V hepatectomy six months after liver lesion identification. The segment IV lesion was histologically proven to be a liver metastasis adenocarcinoma. The segment V lesion revealed a silk thread on the residual liver side at the initial hepatectomy, which was histologically diagnosed as a foreign body granuloma. The possibility of intrahepatic foreign body granuloma development should be considered in subsequent follow-ups in cases where sutures were applied to the dissected residual liver plane during the initial hepatectomy. Additionally, a thorough second hepatectomy should be considered if recurrence is suspected.
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Understanding anatomical anomalies of the branch of the celiac artery for safe gastrectomy is important. We report a case of laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer with a vascular anatomical anomaly of the celiac artery. A 45-year-old woman was referred to our hospital because of early gastric cancer. Computed tomography showed an anatomical variation of the gastroduodenal artery, which branched from the celiac artery. The celiac artery also branched into the left gastric artery, the splenic artery, and the common hepatic artery. Preoperative understanding of an unusual branch of the celiac artery enabled a safe laparoscopic surgery. There were no postoperative complications. The Adachi classification or Michel classification is used for an anatomical anomaly of the celiac artery, but to the best of our knowledge, this case has not been previously classified and is the first reported case.
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Anormalidades Cardiovasculares , Laparoscopia , Neoplasias Gástricas , Feminino , Humanos , Pessoa de Meia-Idade , Artéria Celíaca/diagnóstico por imagem , Artéria Celíaca/cirurgia , Artéria Celíaca/patologia , Artéria Hepática/cirurgia , Artéria Hepática/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Gastrectomia/métodos , Artéria Esplênica/patologia , Anormalidades Cardiovasculares/cirurgiaRESUMO
Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.
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Resistencia a Medicamentos Antineoplásicos , Exossomos , Regulação Neoplásica da Expressão Gênica , Proteínas Mad2 , MicroRNAs , Paclitaxel , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/metabolismo , Exossomos/genética , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Linhagem Celular Tumoral , Masculino , Feminino , Proteínas Mad2/metabolismo , Proteínas Mad2/genética , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Idoso , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagemRESUMO
BACKGROUND/AIM: Ferroptosis is a nonapoptotic type of cell death that is dependent on iron and involves the accumulation of reactive oxygen species. Ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) are ferroptosis regulators that inhibit ferroptosis through independent pathways. This study assessed the prognostic value of GPX4 and FSP1 expression in colorectal cancer (CRC). We also examined the effects of FSP1 and GPX4 inhibition on cell survival of CRC cells. MATERIALS AND METHODS: This study included 206 surgical specimens from Stage II or III CRC patients. FSP1 and GPX4 expression was analyzed immunohistochemically, and the association of their expression levels with clinical outcome was evaluated. We also examined the effects of FSP1 and GPX4 inhibitors on the cell proliferative capacity of CRC cell lines. RESULTS: Overall survival and recurrence-free survival were reduced in patients with high expression of FSP1 or GPX4, and those with both GPX4 and FSP1 expression showed worse prognosis. Positivity of both FSP1 and GPX4 was an independent poor prognostic factor for CRC patients. In CRC cells, the combination of GPX4 and FSP1 inhibitors led to more effective cell death than either inhibitor alone. CONCLUSION: High expression of both GPX4 and FSP1 is a significant poor prognostic factor for CRC. Simultaneous inhibition of GPX4 and FSP1 to induce ferroptosis may be a novel therapeutic strategy in CRC.
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Neoplasias Colorretais , Ferroptose , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Feminino , Masculino , Ferroptose/efeitos dos fármacos , Idoso , Pessoa de Meia-Idade , Prognóstico , Linhagem Celular Tumoral , Proliferação de Células , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/genéticaRESUMO
The presence of smooth muscle at the basal portion of a caudal appendage is very rare. We report a 3-month-old girl in which a caudal appendage is associated with smooth muscle bundles at the perianal region. Immunohistochemistry was performed for NCAM (neural cell adhesion molecule) to identify smooth muscle. NCAM immunoreactivity was observed within the presumptive circular and/or longitudinal muscle layers of the muscularis propria. NCAM is expressed by smooth muscle during the early stages of human embryonic gut development, suggesting that the caudal appendage in the present case may be derived from a tailgut remnant.
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Anormalidades do Sistema Digestório/patologia , Actinas/metabolismo , Canal Anal/patologia , Anormalidades do Sistema Digestório/metabolismo , Feminino , Humanos , Lactente , Músculo Liso/anormalidades , Músculo Liso/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Região SacrococcígeaRESUMO
Background: In recent years, the number of neonatal surgeries has been on the rise despite the decline in the number of births, and we examined the actual trends and problems at Tottori University Hospital located in the Sanin region. Methods: Medical records were retrospectively searched for patients who underwent major surgery during the neonatal period (within 30 days of age) at the Tottori University Hospital over the past 10 years (Jan. 2011 to Dec. 2020). Results: Sixty-five cases were included. Early birth infants (< 37 gestational weeks) comprised 15 cases (23%) and low birth weight (< 2500 g) infants involved 27 cases (42%). In the latter half (2016-2020), early birth and low birth weight infants were significantly less than in the first half (2011-2015). The common diseases were anorectal malformation (14 cases), esophageal atresia (10), duodenal atresia (10), and diaphragmatic hernia (9). Prenatal diagnosis was obtained in 26 cases (40%), with high diagnostic rate obtained in duodenal atresia (100%), abdominal wall defect (100%), ileal atresia (75%), meconium peritonitis (67%), and diaphragmatic hernia (67%). Fifty-five cases (85%) were operated on within 7 days of age. Other major malformations were associated in 23 cases (35%). There were 6 deaths (9%), of which 3 cases were low birth weight infants with gastrointestinal perforation, 2 cases with severe chromosomal abnormalities (esophageal atresia, omphalocele), and 1 case with diaphragmatic hernia with severe pulmonary hypertension. Home medical care has been required with gastrostomy tube in 2 cases. Conclusion: Neonatal surgery at Tottori University has been well performed as required with acceptable results along with the progression of other perinatal care. However, further investigation for improvements in premature delivery or organ hypoplasia may be required.
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[This corrects the article DOI: 10.33160/yam.2023.11.003.].
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Background: Esophagectomy is an invasive and complication-prone surgical procedure. Therefore, a tool that can predict the occurrence of postoperative complications may be useful for perioperative management. In this study, we investigated whether the modified frailty index (mFI) could be a useful tool for predicting the postoperative complications of esophagectomy. Methods: In this study, 162 patients who underwent curative esophagectomy for esophageal squamous cell carcinoma from 2004 to 2019 at our institution were included. The patients were divided into the high mFI (≥ 0.27) and low mFI (< 0.27) groups, and the short-term postoperative outcomes of each group were examined retrospectively. Results: Regarding background factors, age and the American Society of Anesthesiologists physical status classification were significantly higher in the high mFI group (P = 0.049 and P = 0.002, respectively); however, the other items were not significantly different between the two groups. Regarding surgical outcomes, no significant differences in operative time, blood loss, and hospital stay were observed between the two groups. Regarding postoperative complications, pneumonia was significantly more common in the high mFI group (P = 0.035). In multivariate analysis, high mFI (P = 0.034) was an independent predictor of pneumonia, along with operative time ≥ 613 min (P = 0.03) and preoperative BMI < 20.48 (P = 0.006). Conclusion: The mFI is useful for predicting pneumonia after esophagectomy.
RESUMO
BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density (BMD), has been reported as a prognostic factor in patients with digestive tract cancers. However, the correlation between preoperative osteopenia and the prognosis of gastric cancer (GC) remains unclear. The aim of this study was to reveal the importance of preoperative osteopenia as a prognostic factor in patients undergoing gastrectomy for GC. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. BMD was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Osteopenia had a high area under the curve and predictive value for both overall survival (OS) and disease-specific survival (DSS). The study cohort was categorized into an osteopenia group and non-osteopenia group based on the optimal BMD cutoff values for OS (157.5) and DSS (195) determined by receiver operating characteristic analysis. The multivariate analysis revealed that OS (hazard ratio=3.607, p<0.001) and DSS (hazard ratio=2.797, p=0.03) were significantly worse in patients with than without preoperative osteopenia. CONCLUSION: Preoperative osteopenia is associated with poor OS and DSS in patients undergoing gastrectomy for GC.