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1.
Langenbecks Arch Surg ; 409(1): 47, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38267769

RESUMO

AIM: Patients with malignant tumors are prone to develop nutritional disorders. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic indicator for assessing the nutritional status. This study was performed to evaluate whether the preoperative GNRI can serve as a prognostic factor in patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative surgery. METHODS: This study included 123 consecutive patients with ICC who were treated with curative surgery. Kaplan-Meier analysis was performed to calculate the recurrence-free survival (RFS) and overall survival (OS), and Cox regression analysis was used to evaluate prognostic factors. RESULTS: Of the 123 patients, 82 were male and 41 were female. The median age of the patients was 70 years, and the median follow-up period was 37.0 months (interquartile range, 16.2-71.7 months). The patients were classified by the median GNRI into a low GNRI group (GNRI < 105) and high GNRI group (GNRI ≥ 105). The patients in the low GNRI group had a significantly poorer prognosis in terms of RFS and OS than the patients in the high GNRI group (RFS, p = 0.0201; OS, p < 0.0001). Lymph node metastasis [hazard ratio (HR), 4.66; 95% confidence interval (CI), 2.46-8.85], postoperative complications (HR, 2.38; 95% CI, 1.32-4.31), and a low GNRI (HR, 2.53; 95% CI, 1.42-4.50) were independent poor prognostic factors for OS. CONCLUSION: The GNRI may be a useful prognostic indicator in patients with ICC undergoing curative hepatectomy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Feminino , Masculino , Idoso , Lactente , Pré-Escolar , Criança , Hepatectomia , Prognóstico , Estudos Retrospectivos , Colangiocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos
2.
Int J Clin Oncol ; 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39438421

RESUMO

BACKGROUND: The association between aspirin and hepatocellular carcinoma (HCC) has been reported to prevent carcinogenesis caused by hepatitis B or C virus infection. The objective of this study was to investigate the prognostic impact of aspirin in patients who underwent liver resection for HCC. METHODS: Data for 1032 patients who underwent primary resection for HCC between 2000 and 2019 were reviewed. There were 87 patients (8.4%) who took aspirin (aspirin group) and 945 (91.6%) who did not (non-aspirin group). Short-term outcomes, recurrence-free survival (RFS), and overall survival (OS) were compared between two groups in the matched cohort using propensity-score matching. RESULTS: The median patient follow-up was 42.6 months (95% confidence interval 3.12-136.8 months). There was no significant difference in short-term outcomes, including bleeding events. RFS and OS after liver resection in the aspirin group were significantly better than those in the non-aspirin group in the unmatched cohort [5-year RFS rate: 50.3% vs 31.4%, hazard ratio (HR) 0.55, P = 0.0002; 5-year OS rate: 82.9% vs 70.2%, HR 0.46, P = 0.002]. In the matched cohort, RFS and OS after liver resection in the aspirin group were also significantly better than those in the non-aspirin group (5-year RFS rate: 50.3% vs 32.0%, HR 0.60, P = 0.003; 5-year OS rate: 82.9% vs 74.6%, HR 0.56, P = 0.03). CONCLUSION: Use of aspirin was associated with better prognosis for patients who underwent primary resection for HCC.

3.
Br J Cancer ; 128(5): 844-856, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36536047

RESUMO

BACKGROUND: Hyperglycaemia is a well-known initial symptom in patients with pancreatic ductal adenocarcinoma (PDAC). Metabolic reprogramming in cancer, described as the Warburg effect, can induce epithelial-mesenchymal transition (EMT). METHODS: The biological impact of hyperglycaemia on malignant behaviour in PDAC was examined by in vitro and in vivo experiments. RESULTS: Hyperglycaemia promoted EMT by inducing metabolic reprogramming into a glycolytic phenotype via yes-associated protein (YAP)/PDZ-binding motif (TAZ) overexpression, accompanied by GLUT1 overexpression and enhanced phosphorylation Akt in PDAC. In addition, hyperglycaemia enhanced chemoresistance by upregulating ABCB1 expression and triggered PDAC switch into pure basal-like subtype with activated Hedgehog pathway (GLI1 high, GATA6 low expression) through YAP/TAZ overexpression. PDAC is characterised by abundant stroma that harbours tumour-promoting properties and chemoresistance. Hyperglycaemia promotes the production of collagen fibre-related proteins (fibronectin, fibroblast activation protein, COL1A1 and COL11A1) by stimulating YAP/TAZ expression in cancer-associated fibroblasts (CAFs). Knockdown of YAP and/or TAZ or treatment with YAP/TAZ inhibitor (K975) abolished EMT, chemoresistance and a favourable tumour microenvironment even under hyperglycemic conditions in vitro and in vivo. CONCLUSION: Hyperglycaemia induces metabolic reprogramming into glycolytic phenotype and promotes EMT via YAP/TAZ-Hedgehog signalling axis, and YAP/TAZ could be a novel therapeutic target in PDAC.


Assuntos
Carcinoma Ductal Pancreático , Hiperglicemia , Neoplasias Pancreáticas , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Hedgehog/genética , Proteínas de Sinalização YAP , Fatores de Transcrição/genética , Transativadores/genética , Transição Epitelial-Mesenquimal , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Fenótipo , Microambiente Tumoral , Neoplasias Pancreáticas
4.
Langenbecks Arch Surg ; 408(1): 220, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261545

RESUMO

PURPOSE: Colorectal perforation is a fatal disease that presents with generalized peritonitis, leading to sepsis and septic shock. Recently, the association between prolonged door-to-antibiotics time and increased mortality in sepsis has been widely reported. In this study, we investigated the prognostic impact of a prolonged door-to-antibiotics time in patients with perforated colorectal peritonitis undergoing emergency surgery. METHODS: This retrospective study included 93 patients with perforated colorectal peritonitis who underwent emergency surgery at our institution between April 2015 and August 2019. Patients were divided into two groups depending on the door-to-antibiotics time (< 162 min or ≥ 162 min). The primary outcome was in-hospital mortality. The secondary outcomes were the length of hospital stay and severe complication rate. The logistic regression analysis was used to estimate the odds ratio for in-hospital mortality. RESULTS: We identified 38 patients who presented with an extended door-to-antibiotics time (≥ 162 min) and 55 patients who presented with a shortened door-to-antibiotics time (< 162 min). We found a strong association between the door-to-antibiotics time ≥ 162 min and in-hospital mortality. There were no significant differences between the two groups regarding the length of hospital stay and postoperative complication rate. However, in multivariate analysis, extended door-to-antibiotics time was an independent prognostic factor for in-hospital mortality (odds ratio = 244; 95% confidence interval, 11 -23,885). CONCLUSION: A prolonged door-to-antibiotics time (≥ 162 min) worsened hospital mortality rates in patients with perforated colorectal peritonitis.


Assuntos
Neoplasias Colorretais , Perfuração Intestinal , Peritonite , Sepse , Humanos , Mortalidade Hospitalar , Estudos Retrospectivos , Peritonite/cirurgia , Peritonite/complicações , Neoplasias Colorretais/complicações , Perfuração Intestinal/cirurgia , Perfuração Intestinal/complicações , Resultado do Tratamento
5.
Gan To Kagaku Ryoho ; 50(13): 1928-1930, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38303255

RESUMO

In this study, we report a case in which molecular-targeted agents have been shown to be effective in the treatment of unresectable hepatocellular carcinoma(HCC), which has enabled a radical treatment, conversion therapy, and long-term survival with multimodality treatment including RFA. Case: A 61-year-old male, abdominal ultrasonography revealed a large liver tumor and multiple lesions mainly in the right lobe of the liver. He was diagnosed as having unresectable HCC, and treatment with sorafenib was initiated. After treatment, the tumor was clearly reduced in size and the lung metastases disappeared. Five years later, recurrence was observed at the treated site of S7/8, and RFA was performed again after TACE. The patient has survived for 8 years without recurrence.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Terapia de Alvo Molecular , Resultado do Tratamento , Sorafenibe , Terapia Combinada
6.
Surg Today ; 52(7): 1008-1015, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35083547

RESUMO

PURPOSES: The present study investigated the prognostic value of inflammation-based prognostic scores in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. METHODS: In total, 493 patients diagnosed HCC using the Milan criteria who underwent hepatic resection were retrospectively analyzed. Patients were evaluated according to several prognostic nutrition indices. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with the overall survival (OS). RESULTS: According to a univariate analysis, higher values in the Glasgow Prognostic Score [GPS] (hazard ratio [HR] = 1.99, p = 0.002), modified GPS [mGPS] (HR = 2.26, p < 0.001), C-reactive protein [CRP]-to-albumin ratio [CAR] (HR = 1.86, p = 0.0012), and CONUT (HR = 1.65, p = 0.008) and a lower value of prognostic nutritional index [PNI] (HR = 2.36, p < 0.001) were significantly associated with a poor OS. A multivariate analysis showed that a CAR ≥ 0.037 (HR = 1.67, 95% CI 1.06-2.64, p = 0.03), FIB4-index > 3.25 (HR = 1.98, 95% confidence interval [CI] 1.25-3.14, p = 0.004) and PIVKA-II > 40 mAU/ml (HR = 1.72, 95% CI 1.14-2.61, p = 0.01) were independent prognostic factors. CONCLUSIONS: This study demonstrated that the CAR was an independent prognostic score in patients with HCC and superior to other inflammation-based prognostic scores in terms of the prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatectomia , Humanos , Inflamação , Prognóstico , Estudos Retrospectivos
7.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 72(9): 727-34, 2016 09.
Artigo em Japonês | MEDLINE | ID: mdl-27647595

RESUMO

American Association of Physicists in Medicine (AAPM) Report No.204 recommends the size-specific dose estimates (SSDE), wherein SSDE=computed tomography dose index-volume (CTDIvol )×size correction factor (SCF), as an index of the CT dose to consider patient thickness. However, the study on SSDE has not been made yet for area detector CT (ADCT) device such as a 320-row CT scanner. The purpose of this study was to evaluate the SCF values for ADCT by means of a simulation technique to look into the differences in SCF values due to beam width. In the simulation, to construct the geometry of the Aquilion ONE X-ray CT system (120 kV), the dose ratio and the effective energies were measured in the cone angle and fan angle directions, and these were incorporated into the simulation code, Electron Gamma Shower Ver.5 (EGS5). By changing the thickness of a PMMA phantom from 8 cm to 40 cm, CTDIvol and SCF were determined. The SCF values for the beam widths in conventional and volume scans were calculated. The differences among the SCF values of conventional, volume scans, and AAPM were up to 23.0%. However, when SCF values were normalized in a phantom of 16 cm diameter, the error tended to decrease for the cases of thin body thickness, such as those of children. It was concluded that even if beam width and device are different, the SCF values recommended by AAPM are useful in clinical situations.


Assuntos
Tecnologia Radiológica/instrumentação , Tecnologia Radiológica/métodos , Método de Monte Carlo , Doses de Radiação , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/métodos
8.
Phys Med Biol ; 69(10)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700988

RESUMO

Liew and Mairani commented on our paper 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation' (Shiraishiet al2024aPhys. Med. Biol.69015017), which proposed a biophysical model to predict the dose-response curve of surviving cell fractions after ultra-high dose rate irradiation following conventional dose rate irradiation by considering DNA damage yields. They suggested the need to consider oxygen concentration in our prediction model and possible issues related to the data selection process used for the benchmarking test in our paper. In this reply, we discuss the limitations of both the present model and the available experimental data for determining the model's parameters. We also demonstrate that our proposed model can reproduce the experimental survival data even when using only the experimental DNA damage data measured reliably under normoxic conditions.


Assuntos
Sobrevivência Celular , Dano ao DNA , Relação Dose-Resposta à Radiação , Modelos Biológicos , Sobrevivência Celular/efeitos da radiação , Doses de Radiação , Humanos , Oxigênio/metabolismo
9.
Radiol Phys Technol ; 17(1): 11-23, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38184508

RESUMO

FLASH radiotherapy (FLASH-RT) has great potential to improve patient outcomes. It delivers radiation doses at an ultra-high dose rate (UHDR: ≥ 40 Gy/s) in a single instant or a few pulses. Much higher irradiation doses can be administered to tumors with FLASH-RT than with conventional dose rate (0.01-0.40 Gy/s) radiotherapy. UHDR irradiation can suppress toxicity in normal tissues while sustaining antitumor efficiency, which is referred to as the FLASH effect. However, the mechanisms underlying the effects of the FLASH remain unclear. To clarify these mechanisms, the development of simulation models that can contribute to treatment planning for FLASH-RT is still underway. Previous studies indicated that transient oxygen depletion or augmented reactions between secondary reactive species produced by irradiation may be involved in this process. To discuss the possible mechanisms of the FLASH effect and its clinical potential, we summarized the physicochemical, chemical, and biological perspectives as well as the development of simulation modeling for FLASH-RT.


Assuntos
Radioterapia , Humanos , Simulação por Computador , Dosagem Radioterapêutica
10.
Phys Med Biol ; 69(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38056015

RESUMO

Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s-1) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s-1have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed anintegrated microdosimetric-kinetic(IMK)model for UHDR-irradiationenabling the prediction of surviving fraction after UHDR irradiation.Approach.TheIMK model for UHDR-irradiationconsiders the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate.Main results.The estimate by the developed model could successfully reproduce thein vitroexperimental dose-response curve for various cell line types and dose rates.Significance.The developed model would be useful for predicting the biological effects under the UHDR irradiation.


Assuntos
Dano ao DNA , Reparo do DNA , Linhagem Celular , Cinética , Tolerância a Radiação , Dosagem Radioterapêutica
11.
Cancers (Basel) ; 15(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36672448

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type as it is prone to metastases and is difficult to diagnose at an early stage. Despite advances in molecular detection, its clinical prognosis remains poor and it is expected to become the second leading cause of cancer-related deaths. Approximately 85% of patients develop glucose metabolism disorders, most commonly diabetes mellitus, within three years prior to their pancreatic cancer diagnosis. Diabetes, or glucose metabolism disorders related to PDAC, are typically associated with insulin resistance, and beta cell damage, among other factors. From the perspective of molecular regulatory mechanisms, glucose metabolism disorders are closely related to PDAC initiation and development and to late invasion and metastasis. In particular, abnormal glucose metabolism impacts the nutritional status and prognosis of patients with PDAC. Meanwhile, preliminary research has shown that metformin and statins are effective for the prevention or treatment of malignancies; however, no such effect has been shown in clinical trials. Hence, the causes underlying these conflicting results require further exploration. This review focuses on the clinical significance of glucose metabolism disorders in PDAC and the mechanisms behind this relationship, while also summarizing therapeutic approaches that target glycolysis.

12.
Int Cancer Conf J ; 12(3): 195-199, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37251010

RESUMO

Hepatic granuloma is relatively rare, and benign tumor of the liver. Herein, we report an unusual case of hepatic granuloma mimicking intrahepatic cholangiocarcinoma (ICC). An 82-year-old woman with a history of viral hepatitis B was admitted for investigation of liver mass in the left lobe. Dynamic computed tomography revealed a mostly hypo-enhancing main tumor with a peripheral ring enhancement, and positron emission tomography demonstrated localized an abnormal accumulation of fludeoxyglucose. Considering the possibility of malignant disease, extended left hepatectomy was performed. The resected tumor was macroscopically a periductal infiltrating nodular type, 4.5 × 3.6 cm in diameter. The pathological findings showed that granuloma and coagulative necrosis were present, and diagnosis of hepatic granuloma was confirmed. Pathological studies demonstrated that periodic acid-Schiff stain, Grocott-Gomori stain and Ziehl-Neelsen stain were all negative in the lesion.

13.
Am J Cancer Res ; 13(5): 2041-2054, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293171

RESUMO

Statins are cholesterol-lowering agents that act as inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzymeA (HMG CoA) reductase. Recently, statins have received a lot of attention, especially regarding how statins act on the immune system. Here, the clinical impact of statin intake was examined in patients with resected pancreatic cancer, and the underlying mechanisms were investigated in vitro and in vivo. We found that statin intake was associated with favorable prognostic outcomes in patients with resectable pancreatic cancer. Statins, especially lipophilic statins, exert anti-proliferative effects on pancreatic cancer cells in vitro (simvastatin > fluvastatin > atorvastatin > rosuvastatin > pravastatin). Simvastatin had an anti-proliferative effect on pancreatic cancer cells with decreased the yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression by activating the JNK pathway, and simvastatin treatment with oxaliplatin revealed additive anti-growth effects. Furthermore, lipophilic and hydrophilic statins suppressed programmed cell death ligand 1 (PD-L1) expression by downregulating TAZ. Simvastatin treatment with an anti-PD-1 drug (BP0273) provided immediate anti-growth effects compared to controls, such as anti-PD-1 only and simvastatin only, and suppressed progressive disease during the early period of anti-PD-1 treatment in vivo. In conclusion, Statins display two distinct anti-cancer effects (direct anti-growth effect and elimination of immune suppression by downregulating PD-L1 expression) by targeting YAP/TAZ expression.

14.
Clin J Gastroenterol ; 15(6): 1136-1144, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36038805

RESUMO

The presence of neuroendocrine liver metastases is one of the poorest prognostic factors in patients with pancreatic neuroendocrine neoplasms, and surgical resection of neuroendocrine liver metastases is the only curable treatment. A 38-year-old man had a pancreatic neuroendocrine neoplasm with synchronous multiple liver metastases, and two surgeries and continuous everolimus and octreotide achieved R0 resection. However, multiple neuroendocrine liver metastases developed twice after more than 5 years of recurrence-free survival. Aggressive repeat hepatectomy was performed and he has survived for more than 10 years after the initial surgery. This report highlights that patients with pancreatic neuroendocrine neoplasms have a potential risk of recurrence even after 5 years of recurrence-free survival. In addition, combined aggressive hepatectomy and continuous medication can contribute dramatically to long-term survival even for late-stage recurrence of liver metastases.


Assuntos
Neoplasias Hepáticas , Segunda Neoplasia Primária , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Masculino , Humanos , Adulto , Hepatectomia , Octreotida/uso terapêutico , Everolimo/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Segunda Neoplasia Primária/cirurgia , Recidiva Local de Neoplasia/patologia
15.
World J Hepatol ; 14(1): 234-243, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35126851

RESUMO

BACKGROUND: Laparoscopic surgery has been introduced as a minimally invasive technique for the treatment of various field. However, there are few reports that have scientifically investigated the minimally invasive nature of laparoscopic liver resection (LLR). AIM: To investigate whether LLR is scientifically less invasive than open liver resection. METHODS: During December 2011 to April 2015, blood samples were obtained from 30 patients who treated with laparoscopic (n = 10, 33%) or open (n = 20, 67%) partial liver resection for liver tumor. The levels of serum interleukin-6 (IL-6) and plasma thrombospondin-1 (TSP-1) were measured using ELISA kit at four time points including preoperative, immediate after operation, postoperative day 1 (POD1) and POD3. Then, we investigated the impact of the operative approaches during partial hepatectomy on the clinical time course including IL-6 and TSP-1. RESULTS: Serum level of IL-6 on POD1 in laparoscopic hepatectomy was significantly lower than those in open hepatectomy (8.7 vs 30.3 pg/mL, respectively) (P = 0.003). Plasma level of TSP-1 on POD3 in laparoscopic hepatectomy was significantly higher than those in open hepatectomy (1704.0 vs 548.3 ng/mL, respectively) (P = 0.009), and have already recovered to preoperative level in laparoscopic approach. In patients with higher IL-6 Levels on POD1, plasma level of TSP-1 on POD3 was significantly lower than those in patients with lower IL-6 Levels on POD1. Multivariate analysis showed that open approach was the only independent factor related to higher level of IL-6 on POD1 [odds ratio (OR), 7.48; 95% confidence interval (CI): 1.28-63.3; P = 0.02]. Furthermore, the higher level of serum IL-6 on POD1 was significantly associated with lower level of plasm TSP-1 on POD3 (OR, 5.32; 95%CI: 1.08-32.2; P = 0.04) in multivariate analysis. CONCLUSION: In partial hepatectomy, laparoscopic approach might be minimally invasive surgery with less IL-6 production compared to open approach.

16.
Transl Oncol ; 26: 101533, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36115074

RESUMO

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma and cancer-associated fibroblasts (CAFs) provide a favorable tumor microenvironment. Smad4 is known as tumor suppressor in several types of cancers including PDAC, and loss of Smad4 triggers accelerated cell invasiveness and metastatic potential. The thrombospondin-1 (TSP-1) can act as a major activator of latent transforming growth factor-ß (TGF-ß) in vivo. However, the roles of TSP-1 and the mediator of Smad4 loss and TGF-ß signal activation during PDAC progression have not yet been addressed. The aim is to elucidate the biological role of TSP-1 in PDAC progression. METHODS AND RESULTS: High substrate stiffness stimulated TSP-1 expression in CAFs, and TSP-1 knockdown inhibited cell proliferation with suppressed profibrogenic and activated stroma-related gene expressions in CAFs. Paracrine TSP-1 treatment for PDAC cells promoted cell proliferation and epithelial mesenchymal transition (EMT) with activated TGF-ß signals such as phosphorylated Akt and Smad2/3 expressions. Surprisingly, knockdown of DPC4 (Smad4 gene) induced TSP-1 overexpression with TGF-ß signal activation in PDAC cells. Interestingly, TSP-1 overexpression also induced downregulation of Smad4 expression and enhanced cell proliferation in vitro and in vivo. Treatment with LSKL peptide, which antagonizes TSP-1-mediated latent TGF-ß activation, attenuated cell proliferation, migration and chemoresistance with enhanced apoptosis in PDAC cells. CONCLUSIONS: TSP-1 derived from CAFs stimulates loss of Smad4 expression in cancer cells and accelerates malignant behavior by TGF-ß signal activation in PDAC. TSP-1 could be a novel therapeutic target, not only for CAFs in stiff stroma, but also for cancer cells in the PDAC microenvironment.

17.
Front Oncol ; 11: 700315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395269

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer. Despite major advances in defining the molecular mutations driving PDAC, this disease remains universally lethal with an overall 5-year survival rate of only about 7-8%. Genetic alterations in PDAC are exemplified by four critical genes (KRAS, TP53, CDKN2A, and SMAD4) that are frequently mutated. Among these, KRAS mutation ranges from 88% to 100% in several studies. Hippo signaling is an evolutionarily conserved network that plays a key role in normal organ development and tissue regeneration. Its core consists of the serine/threonine kinases mammalian sterile 20-like kinase 1 and 2 (MST1/2) and large tumor suppressor 1 and 2. Interestingly, pancreas-specific MST1/2 double knockout mice have been reported to display a decreased pancreas mass. Many of the genes involved in the Hippo signaling pathway are recognized as tumor suppressors, while the Hippo transducers Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are identified as oncogenes. By dephosphorylation, YAP and TAZ accumulate in the nucleus and interact with transcription factors such as TEA domain transcription factor-1, 2, 3, and 4. Dysregulation of Hippo signaling and activation of YAP/TAZ have been recognized in a variety of human solid cancers, including PDAC. Recent studies have elucidated that YAP/TAZ play a crucial role in the induction of acinar-to-ductal metaplasia, an initial step in the progression to PDAC, in genetically engineered mouse models. YAP and TAZ also play a key role in the development of PDAC by both KRAS-dependent and KRAS-independent bypass mechanisms. YAP/TAZ have become extensively studied in PDAC and their biological importance during the development and progression of PDAC has been uncovered. In this review, we summarize the biological significance of a dysregulated Hippo signaling pathway or activated YAP/TAZ in PDAC and propose a role for YAP/TAZ as a therapeutic target.

18.
Surg Case Rep ; 7(1): 109, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33939052

RESUMO

BACKGROUND: Subtotal cholecystectomy in patients with severe acute cholecystitis is considered a "bailout" option when the safety of the bile duct cannot be guaranteed. However, subtotal cholecystectomy has a long-term risk of remnant cholecystitis. The appropriate management of remnant cholecystitis has not been fully elucidated. CASE PRESENTATION: Case 1 was a 66-year-old man who had undergone subtotal cholecystectomy 14 years prior to the development of remnant cholecystitis. We first performed endoscopic gallbladder drainage to minimize inflammation, and then proceeded with elective surgery. We performed a reconstituting procedure for the residual gallbladder due to significant adhesions between the cystic and common bile ducts. Case 2 was a 56-year-old man who had undergone subtotal cholecystectomy for abscess-forming perforated cholecystitis 2 years prior to the development of remnant cholecystitis. He underwent endoscopic drainage followed by complete remnant cholecystectomy 4 months later. CONCLUSION: Endoscopic gallbladder drainage is a useful strategy to improve inflammation and reduce the risk of bile duct injury during remnant cholecystectomy.

19.
World J Gastroenterol ; 27(43): 7480-7496, 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34887644

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal type of cancer. The 5-year survival rate for patients with early-stage diagnosis can be as high as 20%, suggesting that early diagnosis plays a pivotal role in the prognostic improvement of PDAC cases. In the medical field, the broad availability of biomedical data has led to the advent of the "big data" era. To overcome this deadly disease, how to fully exploit big data is a new challenge in the era of precision medicine. Artificial intelligence (AI) is the ability of a machine to learn and display intelligence to solve problems. AI can help to transform big data into clinically actionable insights more efficiently, reduce inevitable errors to improve diagnostic accuracy, and make real-time predictions. AI-based omics analyses will become the next alterative approach to overcome this poor-prognostic disease by discovering biomarkers for early detection, providing molecular/genomic subtyping, offering treatment guidance, and predicting recurrence and survival. Advances in AI may therefore improve PDAC survival outcomes in the near future. The present review mainly focuses on recent advances of AI in PDAC for clinicians. We believe that breakthroughs will soon emerge to fight this deadly disease using AI-navigated precision medicine.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Inteligência Artificial , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Genômica , Humanos , Neoplasias Pancreáticas/genética , Medicina de Precisão
20.
Ann Gastroenterol Surg ; 5(3): 373-380, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34095728

RESUMO

AIM: Severe postoperative pleural effusion (sPOPE) after hepatectomy can lead to respiratory distress and may require thoracic drainage, leading to prolonged hospitalization. Preventive chest tube insertion may be useful for patients at high risk for sPOPE. We aimed to develop a predictive model for sPOPE after hepatectomy and evaluate indications for preventive chest tube insertion using our model. METHODS: We evaluated all patients who underwent hepatectomy from 2013 to 2020. Risk factors for sPOPE were used to develop a predictive model for sPOPE, which was validated in a cohort that received preventative chest tube placement postoperatively. RESULTS: A total of 325 patients were analyzed. Thirty-one (9.5%) patients had a preventive chest tube placed at the end of their operation. Twenty-one patients out of the remaining 294 patients developed sPOPE. Multivariate analysis identified resection containing segment 8 [relative risk (RR) 3.24, P = .022], intraoperative bleeding ≥ 500 g (RR 4.02, P = .008), intraoperative diaphragmatic incision (RR 6.96, P = .042) and open hepatectomy (RR 7.51, P = .016) as independently associated with sPOPE. The estimated probability of sPOPE ranged from 0.4% in patients with none of these factors to 73.4% in the presence of all factors. Among the 31 patients who received a preventive chest tube, more patients in the high-risk group defined by the model had postoperative pleural effusions compared to the low-risk group (P = .012). CONCLUSION: Our predictive model for sPOPE using four risk factors allows for reliable prediction and may be useful for selection of preventive chest tube in patients undergoing hepatectomy.

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