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1.
Surg Today ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717598

RESUMO

PURPOSE: Stoma construction and closure are common surgical strategies in patients with colorectal cancer. The present study evaluated the influence of multiple incisional sites resulting from stoma closure on incisional hernia after colorectal cancer surgery. METHODS: The study included 1681 patients who underwent colorectal cancer surgery. Multiple incisional sites were defined as the coexistence of incisions at the midline and stoma closure sites. We retrospectively investigated the relationship between the presence of multiple incisional sites and incisional hernia development in patients with colorectal cancer. RESULTS: Among the 1681 patients, 420 (25%) underwent stoma construction, with a stoma closure-to-construction ratio of 33% (139/420), and 155 (9.2%) developed incisional hernias after colorectal cancer surgery. In the multivariate analysis, female sex (p < 0.001), body mass index (p < 0.001), multiple incisional sites (p = 0.001), wound infection (p = 0.003), and postoperative chemotherapy (p = 0.030) were independent predictors of incisional hernia. In the multiple incisional sites group, the age (p < 0.001), surgical approach (laparoscopic) (p = 0.013), wound infection rate (p = 0.046), small bowel obstruction rate (p < 0.001), and anastomotic leakage rate (p = 0.008) were higher in those in the single incisional site group. CONCLUSIONS: Multiple incisional sites resulting from stoma closure are associated with the development of incisional hernia following colorectal cancer surgery.

2.
Asian J Surg ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38538400

RESUMO

BACKGROUND: The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index is a novel immuno-nutritional biomarker based on the levels of CRP, serum albumin, and lymphocyte count. This study examined the prognostic value of the CALLY index in patients with colorectal cancer undergoing curative surgery. METHODS: Between 2010 and 2017, 578 patients with stage II-III colorectal cancer who underwent curative resection were enrolled. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). We investigated the association of the CALLY index with disease-free survival (DFS) and overall survival (OS). RESULTS: The cutoff value of the CALLY index was determined to be 2. Of the 578 patients, 175 (30%) had a preoperative CALLY index <2. In multivariate analysis, the pre-operative carcinoembryonic antigen (CEA) level (p = 0.003), cell differentiation (p = 0.045), venous invasion (p = 0.036), Tumor-Node-Metastasis stage (p < 0.001), and CALLY index score <2 (p = 0.006) were independent predictors of DFS. Meanwhile, preoperative carbohydrate antigen (CA)19-9 levels (p = 0.019), lymphatic invasion (p = 0.018), preoperative platelet (p = 0.037), and CALLY index score <2 (p = 0.007) were independent predictors of OS. CONCLUSION: The CALLY index may be an independent prognostic biomarker for long-term outcomes in patients with colorectal cancer.

3.
Surg Today ; 54(2): 106-112, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37222815

RESUMO

PURPOSE: Defunctioning loop ileostomy has been reported to reduce symptomatic anastomotic leakage after rectal cancer surgery; however, stoma outlet obstruction (SOO) is a serious postileostomy complication. We, therefore, explored novel risk factors for SOO in defunctioning loop ileostomy after rectal cancer surgery. METHODS: This is a retrospective study that included 92 patients who underwent defunctioning loop ileostomy with rectal cancer surgery at our institution. Among them, 77 and 15 ileostomies were created at the right lower abdominal and umbilical sites, respectively. We defined the output volumeMAX as the maximum output volume the day before the onset of SOO or-for those without SOO-that was observed during hospitalization. Univariate and multivariate analyses were performed to evaluate risk factors for SOO. RESULTS: SOO was observed in 24 cases, and the median onset was 6 days postoperatively. The stoma output volume in the SOO group was consistently higher than that in the non-SOO group. In the multivariate analysis, the rectus abdominis thickness (p < 0.01) and output volumeMAX (p < 0.01) were independent risk factors for SOO. CONCLUSION: A high-output stoma may predict SOO in patients with defunctioning loop ileostomy for rectal cancer. Considering that SOO occurs even at umbilical sites with no rectus abdominis, a high-output stoma may trigger SOO primarily.


Assuntos
Ileostomia , Neoplasias Retais , Humanos , Ileostomia/efeitos adversos , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos , Neoplasias Retais/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
4.
In Vivo ; 37(6): 2678-2686, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905632

RESUMO

BACKGROUND/AIM: The prognostic outcome of the controlling nutritional status (CONUT) score in patients with colorectal liver metastases (CRLM) who underwent hepatectomy has not been investigated. The aim of this study was to investigate the prognostic value of preoperative CONUT score and other systemic inflammation-related biomarkers in patients who underwent hepatectomy for CRLM. PATIENTS AND METHODS: The subjects included 145 patients with CRLM who underwent hepatectomy and retrospectively investigated the association of preoperative CONUT score with disease-free survival (DFS), surgical failure-free survival (SFS), and overall survival (OS) using univariate and multivariate analyses. RESULTS: In this study, the cut-off of the CONUT score was 4. In the univariate analysis, the high CONUT score was associated with worse SFS and OS (p=0.01, 0.01). The multivariate analysis showed significant and independent predictors of OS were lymph node metastases (p=0.03) and a high CONUT score (p=0.04). In patients with a high CONUT score, postoperative complications due to infections were significantly more than in those with a low CONUT score (27% vs. 9%, p=0.04). CONCLUSION: The CONUT score can be useful for predicting not only short-term but also long-term outcomes in patients with CRLM after hepatectomy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Estado Nutricional , Hepatectomia/efeitos adversos , Estudos Retrospectivos , Relevância Clínica , Neoplasias Hepáticas/patologia , Prognóstico , Neoplasias Colorretais/cirurgia
5.
In Vivo ; 36(5): 2461-2464, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099108

RESUMO

BACKGROUND/AIM: Surgery for dialysis patients requires special attention because of their physical characteristics. This study aimed to investigate the short-term postoperative outcomes of colorectal cancer patients with chronic renal failure (CRF) on dialysis and aimed to investigate safer treatment options for these patients. PATIENTS AND METHODS: A total of 1,504 colorectal cancer patients who underwent primary resection between January 2008 and December 2018 were included. A retrospective analysis of clinical data, preoperative tumor markers (carcinoembryonic antigen and carbohydrate antigen 19-9), and the Clavien-Dindo (CD) classification was performed. Patients were stratified into Groups A and B based on their need for dialysis or not, respectively. RESULTS: There were 20 and 1,484 patients in Groups A and B, respectively. No differences were observed regarding age, body mass index, and preoperative tumor markers. The rate of laparoscopic surgery was significantly lower in Group A than in Group B. There was one mortality in Group A due to pulmonary disease. Group A had a significantly higher rate of complications. CONCLUSION: CRF patients on dialysis who underwent colorectal cancer surgery tended to be ruled out of laparoscopic surgery, and their rates of postoperative complications were higher.


Assuntos
Neoplasias Colorretais , Falência Renal Crônica , Biomarcadores Tumorais , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Estudos Retrospectivos
6.
J Clin Med ; 10(22)2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34830719

RESUMO

We reviewed the results of local surgical treatment of stoma prolapse, a long-term complication of stoma construction. Fifteen patients treated for stomal prolapse between 2009 and 2020 at the authors' and affiliated hospitals were included in this study. The treatment comprised local laparotomic stomal reconstruction (LLSR) in nine patients and stapling repair (SR) in six. We compared and evaluated the clinical and surgical information and postoperative complications. Operation time was significantly shorter in the SR group than in the LLSR group: 20 and 53 min, respectively (p = 0.036). The duration of postoperative hospitalization was shorter in the SR group than in the LLSR group: 5.5 and 8 days, respectively; the difference was not significant (p = 0.088). No short-term complications were found in either group. Regarding long-term, postoperative complications, parastomal hernias developed after 2.5 years in one patient in the LLSR group and after 6 months in one patient in the SR group; both patients had histories of parastomal hernia surgery and had relatively high body mass indices. Local surgery for stomal prolapse was minimally invasive and performed safely. In patients with a history of surgery for parastomal hernia, attention must be paid to the potential of parastomal hernia developing as a postoperative complication.

7.
PLoS One ; 16(9): e0257019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473771

RESUMO

Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 µg/mL and 40 µg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.


Assuntos
Benzamidinas/administração & dosagem , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/radioterapia , Guanidinas/administração & dosagem , NF-kappa B/antagonistas & inibidores , Inibidores de Proteases/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Terapia Combinada/métodos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos da radiação , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Ann Gastroenterol Surg ; 5(4): 567-574, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34337305

RESUMO

BACKGROUND: Pancreatic cancer is one of the most aggressive digestive cancers. The tumor expression of thrombomodulin (TM) is correlated with favorable prognosis in several types of cancer. However, this correlation has not been confirmed in hepato-pancreato-biliary cancer. The aim of this study was to evaluate the prognostic value of TM expression in resected pancreatic ductal adenocarcinoma. METHODS: The data of patients who underwent pancreatic resection for pancreatic invasive ductal adenocarcinoma were obtained from a prospectively maintained database. A total of 131 patients were included. Paraffin sections of tumor tissues were stained immunohistochemically using TM antibody. The patients were divided into two groups: the TM-positive or TM-negative group. RESULTS: The specimens were TM-positive in 72 cases. TM expression was a significant factor of favorable prognosis in univariate analysis for disease-free (DFS) and overall survival (OS). The median OS in the TM-positive patients was 32.9 mo, which was better than the 20.0 mo in TM-negative patients (P =.006). TM positivity retained its significance on multivariate analysis for DFS (hazard ratio [HR] 0.651, 95% confidence interval [CI] 0.433-0.979, P =.039) and OS (HR 0.569, 95% CI 0.376-0.862, P =.008). CONCLUSIONS: The tumor expression of TM is a favorable factor for OS in resected pancreatic invasive ductal adenocarcinoma.

10.
Anticancer Res ; 40(6): 3445-3451, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487643

RESUMO

BACKGROUND/AIM: Umbilical defunctioning ileostomy (UDI) spares one incision, which may reduce the overall incidence of incisional hernia. Our aim was to evaluate the occurrence and risk factors of incisional hernias between UDI and conventional defunctioning ileostomy (CDI) after ileostomy closure. PATIENTS AND METHODS: Incidence of incisional hernia after ileostomy closure was compared between UDI (n=51) and CDI (n=86) groups. Risk factors for incisional hernia were also considered through a retrospective analysis. RESULTS: The overall incidence of incisional hernia was 5.9% in the UDI group, which was significantly lower than the 22.1% (7.0% at the midline incision and 15.1% at the stoma site) in the CDI group (p=0.012). Multivariate analysis showed higher BMI (p=0.035) and CDI (p=0.031) as risk factors for developing incisional hernias overall. CONCLUSION: UDI results in fewer incisional hernias than CDI and seems to be superior to CDI from the standpoint of overall incidence of incisional hernias.


Assuntos
Ileostomia/efeitos adversos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias , Neoplasias Retais/complicações , Neoplasias Retais/epidemiologia , Feminino , Humanos , Ileostomia/métodos , Hérnia Incisional/diagnóstico , Laparoscopia/métodos , Tempo de Internação , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Neoplasias Retais/diagnóstico , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Int J Colorectal Dis ; 35(8): 1549-1555, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32382837

RESUMO

PURPOSE: Systemic inflammatory response has been reported to be associated with prognosis in cancer patients. The aim of this study is to investigate the association between Systemic Immune-Inflammation Index (SII), a novel inflammation-based prognostic score and long-term outcomes among patients with colorectal cancer (CRC) after resection. METHODS: We retrospectively investigated 733 patients who underwent resection for CRC between January 2010 and December 2014 at the Jikei University Hospital and explored the relationship between SII, calculated by multiplying the peripheral platelet count by neutrophil count and divided by lymphocyte count, and overall survival. In survival analyses, we conducted Cox proportional hazards models, adjusting potential confounders including TNM stage, serum CEA, serum CA 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and platelet count. RESULTS: In multivariate analysis, age ≥ 65 years (p = 0.003), tumor location (p = 0.043), advanced TNM stage (p < 0.001), serum CA 19-9 > 37 mU/ml (p < 0.001), and SII (P for trend = 0.017) were independent and significant predictors of poor patient survival. Compared to patients with low SII, those with high and intermediate SII patients had poorer survival (Hazard ratio 2.48; 95% CI 1.31-4.69, Hazard ratio 1.65; 95% CI 0.83-3.27, respectively). CONCLUSION: The Systemic Immune-Inflammation Index might be an independent and significant indicator of poor long-term outcomes in patients with CRC after resection.


Assuntos
Neoplasias Colorretais , Inflamação , Idoso , Neoplasias Colorretais/cirurgia , Humanos , Linfócitos , Neutrófilos , Prognóstico , Estudos Retrospectivos
12.
Anticancer Res ; 40(4): 1891-1896, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234877

RESUMO

BACKGROUND/AIM: Advances in stapling devices have led to their widespread use in colorectal surgery. We compared the strength of four types of anastomoses using bursting pressure. MATERIALS AND METHODS: We created stapled anastomosis models [double stapling technique (DST), functional end-to-end anastomosis (FEEA) unbuttressed or buttressed, and triangulating anastomosis (TA) with two- or three-row stapling] and a hand-sewn anastomosis model. Bursting pressures of each method were measured. The primary end point was the bursting pressure. The effectiveness of buttressing and three-row stapling were the secondary endpoints. RESULTS: The DST group had significantly lower bursting pressure than TA with three-row stapling, FEEA buttressed, and hand-sewn groups. No significant difference was found between the bursting pressure of the FEEA unbuttressed and FEEA buttressed groups and that of the TA with two-row and three-row stapling groups. CONCLUSION: DST has the lowest bursting pressure compared to other anastomotic techniques. Buttressing suture and three-row stapling have no effect on the strength of anastomosis.


Assuntos
Anastomose Cirúrgica/métodos , Neoplasias Colorretais/cirurgia , Cirurgia Colorretal/métodos , Grampeamento Cirúrgico/métodos , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Técnicas de Sutura
13.
Surg Today ; 50(7): 743-748, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31974754

RESUMO

PURPOSE: In rectal cancer surgery, an insufficient distal margin (DM) is associated with a high risk of local recurrence, whereas an excessive DM will cause low anterior resection syndrome, impairing quality of life. This study aimed to identify the factors that affect the distance between the colorectal resection site and the tumor to optimize achieving the correct DM. METHODS: The subjects of this study were 219 patients who underwent resection for primary rectal cancer in our department between January 2006 and July 2014. According to Japanese guidelines, DM (rDM) was based on the tumor location, but the pathological DM (pDM) was measured from surgical specimens. The patients were divided into two groups: the pDM-less-than-rDM group (pDM < rDM) and the pDM-greater-or-equal-to-rDM group (pDM ≥ DM). The factors associated with the DM in the two groups were compared. RESULTS: In the pDM < rDM group, the tumor distance from the anal verge was shorter (p = 0.001) and significantly more patients underwent laparotomy (p = 0.047). CONCLUSION: The DM tended to be shorter than that planned by the surgeon in patients with lower rectal cancers and those treated by laparotomy,; therefore, when performing rectal resection, care must be taken to ensure that the pDM is not shorter than the rDM.


Assuntos
Margens de Excisão , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reto/cirurgia , Idoso , Endoscopia Gastrointestinal , Feminino , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Qualidade de Vida , Reto/patologia , Risco
14.
Anticancer Res ; 39(10): 5721-5724, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570473

RESUMO

BACKGROUND/AIM: This study aimed to identify risk factors for recurrence of patients with stage III colorectal cancer by assessing clinicopathological features. PATIENTS AND METHODS: The study included 231 patients with stage III colorectal cancer who underwent curative resection between 2006 and 2012 at the Department of Surgery of the Jikei University Hospital, Tokyo, Japan. Clinicopathological data of the patients were retrospectively evaluated. RESULTS: The recurrence rate was 27.7% (64/231) in the study group. The univariate analysis for recurrence identified five risk factors: site of primary tumor (rectal cancer), surgical procedure (open surgery), preoperative serum CEA level (>5 ng/ml), preoperative serum CA19-9 level (>37 U/ml), and number of metastatic lymph nodes (over three metastases). The multivariate analysis for recurrence identified three risk factors: rectal cancer, preoperative serum CEA level >5.0 ng/ml 95%, and more than three metastatic lymph nodes. CONCLUSION: The risk factors for stage III colorectal cancer recurrence seem to be rectal cancer, preoperative serum CEA level >5.0 ng/ml, and more than three metastatic lymph nodes.


Assuntos
Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Antígeno CA-19-9/metabolismo , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Japão , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
15.
Surgery ; 166(6): 991-996, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31353078

RESUMO

BACKGROUND: Liver metastasis is a common problem after pancreatectomy for pancreatic cancer. In pancreatic cancer cells, nuclear factor-κB is activated constitutively. Nuclear factor-κB activates matrix metalloproteinase-2/9, which plays an important role in cancer metastasis. Because the serine protease inhibitor FUT-175 suppresses nuclear factor-κB, we hypothesized that perioperative treatment with FUT-175 for pancreatic cancer may help to prevent liver metastasis. METHODS: We compared in vitro cell viability, cell invasiveness, nuclear factor-κB signaling, and the expression levels of matrix metalloproteinase signals between the control group (C group) and the FUT-175 group (F group) using the murine pancreatic cancer cells PAN02. In addition, we evaluated the in vivo effect of pretreatment with FUT-175 using an established model of liver metastasis in mice. Metastatic liver lesions were assessed with magnetic resonance imaging. Liver recurrence and overall survival were evaluated. Also, the antimetastatic effect of systemic administration of FUT-175 was examined. RESULTS: FUT-175 did not suppress the cell viability of PAN02 cells at or after 24 hours of treatment (P > .05); however, cell invasion was suppressed in the F group compared with the C group (P < .05). The levels of nuclear factor-κB activation, membrane type-1 (MT-1) matrix metalloproteinase (MMP)/matrix metalloproteinase-14 (MMP-14), and matrix metalloproteinase-2/9 (MMP-2/9) were lower in the F group compared with the C group. In vivo, both disease-free and overall survivals were prolonged in the F group compared with the C group. Systemic administration was also effective in suppressing the number of metastases. CONCLUSION: Perioperative treatment with FUT-175 may help to prevent early liver metastasis after pancreatectomy for pancreatic cancer.


Assuntos
Guanidinas/administração & dosagem , Neoplasias Hepáticas/prevenção & controle , NF-kappa B/antagonistas & inibidores , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Animais , Benzamidinas , Linhagem Celular Tumoral/transplante , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Intervalo Livre de Doença , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Assistência Perioperatória/métodos , Transdução de Sinais/efeitos dos fármacos
17.
Cancers (Basel) ; 10(10)2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30336548

RESUMO

Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for patients with locally advanced low rectal cancer. However, several studies have reported that ionizing radiation (IR) activates nuclear factor kappa B (NF-κB) that causes radioresistance and induces matrix metalloproteinase (MMP)-2/-9, which promote tumor migration and invasion. Nafamostat mesilate (FUT175), a synthetic serine protease inhibitor, enhances the chemosensitivity to cytotoxic agents in digestive system cancer cells by inhibiting NF-κB activation. Therefore, we evaluated the combined effect of IR and FUT175 on cell proliferation, migration and invasion of colorectal cancer (CRC) cells. IR-induced upregulation of intranuclear NF-κB, FUT175 counteracted this effect. Moreover, the combination treatment suppressed cell viability and induced apoptosis. Similar effects were also observed in xenograft tumors. In addition, FUT175 prevented the migration and invasion of cancer cells caused by IR by downregulating the enzymatic activity of MMP-2/-9. In conclusion, FUT175 enhances the anti-tumor effect of radiotherapy through downregulation of NF-κB and reduces IR-induced tumor invasiveness by directly inhibiting MMP-2/-9 in CRC cells. Therefore, the use of FUT175 during radiotherapy might improve the efficacy of radiotherapy in patients with CRC.

18.
Oncotarget ; 9(21): 15780-15791, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29644009

RESUMO

BACKGROUND: Chemotherapy with gemcitabine and nab-paclitaxel (gemcitabine/nab-paclitaxel) is recommended for unresectable pancreatic cancer. However, the therapeutic efficacy is attenuated by the antitumor agent-induced activation of nuclear factor-κB (NF-κB). Thalidomide inhibits NF-κB activation, therefore, we hypothesized that pomalidomide, a third-generation IMiD, would also inhibit NF-κB activation and enhance the antitumor effects of gemcitabine/nab-paclitaxel. METHODS: In vitro, we assessed NF-κB activity and apoptosis in response to pomalidomide alone, gemcitabine/nab-paclitaxel, or combination of pomalidomide and gemcitabine/nab-paclitaxel in human pancreatic cancer cell lines (PANC-1 and MIA PaCa-2). In vivo, we established orthotopic model and the animals were treated with oral pomalidomide and injection of gemcitabine/nab-paclitaxel. RESULTS: In pomalidomide and gemcitabine/nab-paclitaxel group, gemcitabine/nab-paclitaxel-induced NF-κB activation was inhibited and apoptosis was enhanced in comparison with those in the other groups both in vitro and in vivo. Especially, this study revealed for the first time that pomalidomide enhances p53 on pancreatic cancer cells. The tumor growth in the pomalidomide and gemcitabine/nab-paclitaxel group was significantly slower than that in the gemcitabine/nab-paclitaxel group. Moreover, pomalidomide induced G0/G1 cell cycle arrest and suppressed angiogenesis. CONCLUSIONS: Pomalidomide enhanced the antitumor effect of gemcitabine/nab-paclitaxel by inhibition of NF-κB activation. This combination regimen would be a novel strategy for treating pancreatic cancer.

19.
Int J Colorectal Dis ; 33(6): 755-762, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29602975

RESUMO

PURPOSE: Anastomotic leakage (AL) and surgical site infection (SSI) are prevalent complications of colorectal surgery. To lower this risk, we standardized our surgical procedures in 2012, with a preferential use of laparoscopic approach (LS) for both colon and rectal surgery, combined with triangulating anastomosis (TA) for colon surgery and defunctioning ileostomy (DI) for low anterior resection. Our aim was to evaluate the outcomes of our standardized procedures. METHODS: The incidence rate of AL (primary outcome) and of reoperation and SSI (secondary outcome) was compared before (early period, n = 648) and after (late period, n = 541) standardization, through a retrospective analysis. RESULTS: The incidence rate of AL (6.6 versus 1.8%; P = 0.001), reoperation (3.5 versus 0.7%; P = 0.0012), and SSI (7.7 versus 4.6%; P = 0.029) was lower in late than in the early period. For colon cancer, TA and LS reduced the risk of AL (2.1 versus 0.3%, P = 0.020, for TA, and 3.2 versus 0.4%, P = 0.0027, for LS) and reoperation (2.9 versus 0.3%, P = 0.003, for TA, and 2.5 versus 0.2%, P = 0.0040, for LS). For rectal cancer, the incidence of all adverse outcomes (AL, reoperation, and SSI) was lower in cases treated by LS. However, the incidence of AL was lower in the late than in early period (P = 0.002) and with LS (P = 0.002). On multivariate analysis, late period and LS were independent factors of a lower risk of adverse outcomes. CONCLUSIONS: Our surgical standardization seems to be effective in lowering the risks of AL, reoperation, and SSI after colorectal cancer surgery.


Assuntos
Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Neoplasias Colorretais/cirurgia , Cirurgia Colorretal/efeitos adversos , Cirurgia Colorretal/normas , Reoperação/normas , Infecção da Ferida Cirúrgica/etiologia , Idoso , Feminino , Humanos , Ileostomia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Padrões de Referência , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Anticancer Res ; 38(3): 1789-1795, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29491118

RESUMO

BACKGROUND/AIM: Early postoperative small bowel obstruction (EPSBO) prolongs hospital stays after surgery. This study aimed to evaluate the risk factors for EPSBO associated with colorectal cancer resection. PATIENTS AND METHODS: We retrospectively compared the clinical variables of patients with EPSBO (n=37) and those without (n=812) after primary tumor resection for colorectal cancer at our hospital between January 2010 and December 2015. RESULTS: In multivariate analysis, significant differences between the two groups was found in male sex, open surgery, and defunctioning ileostomy (DI) placement (p=0.024, p<0.0001, and p=0.023, respectively), but not for colostomy placement. Of 16 patients with DI who developed EPSBO, 13 (81.3%) cases resulted from obstruction of the stomal outlet. CONCLUSION: Male sex, open surgery, and DI placement are risk factors for EPSBO after colorectal cancer resection. For patients with placement of DI, obstruction of the stomal outlet should be carefully considered.


Assuntos
Neoplasias Colorretais/cirurgia , Ileostomia/métodos , Obstrução Intestinal/cirurgia , Complicações Pós-Operatórias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/complicações , Feminino , Humanos , Ileostomia/efeitos adversos , Obstrução Intestinal/etiologia , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
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