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1.
Int J Clin Oncol ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596803

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are a prognostic factor or an indicator of chemotherapy response for various malignancies. The aim of this study was to investigate the prognostic impact of TILs in resected intrahepatic cholangiocarcinoma (IHCC). We also investigated the usefulness of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) to predict TILs. METHODS: We enrolled 23 patients with IHCC who underwent initial hepatic resection in Tokushima University Hospital from 2006 to 2017. We evaluated stromal TILs in the tumor marginal area and central area in surgical specimens. Patients were divided into low vs high stromal TILs groups. We analyzed the patients' clinicopathological factors, including prognosis, according to the degree of stromal TILs. We also analyzed the correlation between stromal TILs and the minimum ADC value. RESULTS: Stromal TILs in the marginal area reflected overall survival more accurately than that in the central area. Additionally, marginal low TILs was significantly associated with lymph node metastasis and portal vein invasion. Both overall- and disease-free survival rates in the marginal low TILs group were significantly worse than those in the marginal high TILs group (P < 0.05). In the multivariate analysis, marginal low TILs were an independent prognostic factor for both overall- and disease-free survival (P < 0.05), and marginal low TILs were significantly associated with lower minimum ADC values (P < 0.02). CONCLUSIONS: Stromal TILs, especially in the marginal area, might demonstrate prognostic impact in patients with IHCC. Moreover, the ADC values from MRI may predict TILs in IHCC tumor tissue.

2.
PLoS One ; 16(9): e0256755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473785

RESUMO

BACKGROUND AND AIM: As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line. METHODS: A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again. RESULTS: Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced. CONCLUSION: Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34557939

RESUMO

PURPOSE: This study was performed to investigate the potential of intraoperative three-dimensional (3D) holographic cholangiography, which provides a computer graphics model of the biliary tract, with mixed reality techniques. METHODS: Two patients with intraductal papillary neoplasm of the bile duct were enrolled in the study. Intraoperative 3D cholangiography was performed in a hybrid operating room. Three-dimensional polygon data using the acquired cholangiography data were installed into a head mount display (HoloLens; Microsoft Corporation, Redmond, WA, USA). RESULTS: Upon completion of intraoperative 3D cholangiography, a hologram was immediately and successfully made in the operating room using the acquired cholangiography data, and several surgeons wearing the HoloLens succeeded in sharing the same hologram. Compared with usual two-dimensional cholangiography, this 3D holographic cholangiography technique contributed to more accurate reappearance of the bile ducts, especially the B1 origination site, and moving the hologram from the respective operators' angles by means of easy gesture-handling without any monitors. CONCLUSION: Intraoperative 3D holographic cholangiography might be a new next-generation operation-support tool in terms of immediacy, accurate anatomical reappearance, and ease of handling.

4.
Anticancer Res ; 41(9): 4637-4644, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475092

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate frailty as a prognostic factor in patients with colorectal liver metastasis undergoing hepatectomy. PATIENTS AND METHODS: Eighty-seven patients who underwent hepatectomy at our institution were enrolled. Frailty was defined as a score of ≥4 on a clinical frailty scale. Patients were divided into frailty (n=29) and non-frailty (n=58) groups. RESULTS: Overall and cancer-specific survival rates were significantly worse in the frailty group compared with the non-frailty group, and multivariate analysis revealed frailty as an independent prognostic factor. Disease-free survival tended to be worse in the frailty group. Fifty-eight patients relapsed after the first hepatectomy. Twenty-one of 58 recurrent patients were allocated to the frailty group. After recurrence, chemotherapy was significantly more frequently performed in the non-frailty group compared with the frailty group. CONCLUSION: Frailty can predict the prognosis of patients with colorectal liver metastasis undergoing hepatectomy.


Assuntos
Neoplasias Colorretais/cirurgia , Fragilidade/epidemiologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Tratamento Farmacológico , Feminino , Fragilidade/complicações , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
5.
J Hepatobiliary Pancreat Sci ; 28(9): 705-715, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34318615

RESUMO

BACKGROUND: The aim of this study was to clarify the effectiveness of a new three-dimensional (3D) culture system for hepatocyte-like cells (HLCs) generated from human adipose-derived mesenchymal stem cells (ADSCs). METHODS: Human ADSCs (2 × 104 ) with or without 0.1 mg/mL human recombinant peptide µ-piece per well were seeded in a 96-well U-bottom plate and then our three-step differentiation protocol was applied for 21 days. At each step, cell morphology and gene expression were investigated. Mature hepatocyte functions were evaluated after HLC differentiation. These parameters were compared between 2D- and 3D-cultured HLCs, and, DNA microarray analysis was also performed. Finally, HLCs were transplanted in to CCl4 induced acute liver failure model mice. RESULTS: Two-dimensional-cultured HLCs at day 21 did not have a spindle shape and had formed spheroids after day 6, which gradually increased in size for 3D-cultured HLCs. Definitive endoderm, hepatoblast, and hepatocyte genes showed significantly higher expression in the 3D culture group. Three-dimensional-cultured HLCs also had higher albumin expression, CYP3A4 activity, urea synthesis, and ammonium metabolism, and much higher expression of ion transporter, blood coagulation, and cell communication genes. HLC transplantation improved serum liver function, especially in T-Bil levels, and engrafted into immunodeficient mice with HLA class I positive staining. CONCLUSION: Our new 3D culture protocol is effective to improve hepatocyte functions. Our HLCs might be promising for clinical cell transplantation to treat metabolic disease.

6.
Int J Oncol ; 59(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34195849

RESUMO

Targeting the tumor stroma is an important strategy in cancer treatment. Cancer­associated fibroblasts (CAFs) and tumor­associated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor­1 (PAI­1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI­1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells in vitro. It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL­6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI­1 expression was upregulated in TAMs after being stimulated with CAF­conditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelial­mesenchymal transition. CAFs were the main producer of C­X­C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI­1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI­1 secretion via CXCL12. Furthermore, it was found that PAI­1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.

7.
Cancer Sci ; 112(9): 3545-3554, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34159680

RESUMO

The tumor microenvironment affects malignancy in hepatocellular carcinoma (HCC) cells, and cancer-associated fibroblasts (CAFs) play an important role in the microenvironment. As recent studies indicated a difference between CAFs isolated from chemoresistant and non-resistant cancer tissues, therefore we investigated the intracellular mechanism in resistant HCC co-cultured CAFs and interactions between these CAFs with cancer cells. We established a sorafenib-resistant (SR) Huh7 (human HCC) cell line, and characterized it with cytokine assays, then developed CAFs by co-culturing human hepatic stellate cells with resistant or parental Huh7 cells. The 2 types of CAFs were co-cultured with parental Huh7 cells, thereafter the cell viability of these Huh7 cells was checked under sorafenib treatment. The SR Huh7 (Huh7SR ) cells expressed increased B-cell activating factor (BAFF), which promoted high expression of CAF-specific markers in Huh7SR -co-cultured CAFs, showed activated BAFF, BAFF-R, and downstream of the NFκB-Nrf2 pathway, and aggravated invasion, migration, and drug resistance in co-cultured Huh7 cells. When we knocked down BAFF expression in Huh7SR cells, the previously increased malignancy and BAFF/NFκB axis in Huh7SR -co-cultured CAFs reversed, and enhanced chemoresistance in co-cultured Huh7 cells returned as well. In conclusion, the BAFF/NFκB pathway was activated in CAFs co-cultured with cell-culture medium from resistant Huh7, which promoted chemoresistance, and increased the malignancy in co-cultured non-resistant Huh7 cells. This suggests that the BAFF/NFκB axis in CAFs might be a potential therapeutic target in chemoresistance of HCC.


Assuntos
Antineoplásicos/farmacologia , Fator Ativador de Células B/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Hepatocelular/metabolismo , Comunicação Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/genética , Sorafenibe/farmacologia , Fator Ativador de Células B/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Técnicas de Cocultura , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Transfecção
8.
Surg Today ; 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34009433

RESUMO

PURPOSE: To clarify whether the preoperative lymphocyte/C-reactive protein (CRP) ratio (LCR) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (IHCC), and investigate its mechanism via tumor-infiltrating lymphocytes. METHODS: The subjects of this retrospective study were 42 patients who had undergone hepatectomy for IHCC. We divided the patients into low LCR and high LCR groups (cutoff value: 8780) and analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated the levels of stromal tumor-infiltrating lymphocytes (TILs) and CD8+ TILs in surgical specimens, and the relationship between LCR and TILs. RESULTS: A low LCR was identified in 21 patients and was significantly correlated with older age, a high CRP-albumin ratio, and advanced disease stage, and was a prognostic factor for OS and DFS. Multivariate analysis revealed that a low LCR was an independent prognostic factor for worse OS (HR 10.40, P = 0.0077). Although the LCR and levels of stromal TILs were not significantly related, LCR and levels of CD8+ TILs were significantly related (P = 0.0297). CONCLUSION: The preoperative LCR may predict the postsurgical prognosis of patients with IHCC and reflect the CD8+ TILs.

9.
World J Surg Oncol ; 19(1): 142, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962620

RESUMO

BACKGROUND: No universal classification method for intrahepatic cholangiocarcinoma (IHCC) has been reported based on the embryological origin of biliary epithelial cells. The aim of this study was to classify IHCC according to protein expression levels of somatostatin receptor 2 (SSTR2) and b-cell leukemia/lymphoma 2 (Bcl2) and to elucidate the clinicopathological features of each group. METHODS: Fifty-two IHCC patients who underwent hepatic resection were enrolled in this study. Protein expression levels of SSTR2 and Bcl2 were examined using immunohistochemistry. Clinicopathological factors were compared between the three groups and prognostic factors were investigated. RESULTS: The patients were divided into three groups: SSTR2 positive and Bcl2 negative (p-Group H, n = 21), SSTR2 negative and Bcl2 positive (p-Group P, n = 14), and the indeterminate group (p-Group U, n = 17) for cases where SSTR2 and Bcl2 were both positive or both negative. All p-Group P cases displayed curability A or B. The 5-year survival rates of p-Group H and U patients were worse than those in p-Group P. p-Group H had higher T-factor, clinical stage, and incidence of periductal infiltration than p-Group P. CONCLUSIONS: This method could be used to classify IHCC into peripheral and perihilar type by embryological expression patterns of SSTR2 and Bcl2.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Humanos , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2 , Receptores de Somatostatina
10.
Gastroenterology ; 161(1): 151-162.e1, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33819484

RESUMO

BACKGROUND & AIMS: We recently reported use of tissue-based transcriptomic biomarkers (microRNA [miRNA] or messenger RNA [mRNA]) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, we translated our tissue-based biomarkers into a blood-based liquid biopsy assay for noninvasive detection of LNM in patients with high-risk T1 CRC. METHODS: We analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from 2 clinical cohorts-a training cohort (N = 46) and a validation cohort (N = 142)-and matched formalin-fixed paraffin-embedded samples (N = 142). We performed quantitative reverse-transcription polymerase chain reaction, followed by logistic regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model combined with clinical risk factors. RESULTS: We used comprehensive expression profiling of a training cohort of LNM-positive and LMN-negative serum specimens to identify an optimized transcriptomic panel of 4 miRNAs (miR-181b, miR-193b, miR-195, and miR-411) and 5 mRNAs (AMT, forkhead box A1 [FOXA1], polymeric immunoglobulin receptor [PIGR], matrix metalloproteinase 1 [MMP1], and matrix metalloproteinase 9 [MMP9]), which robustly identified patients with LNM (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.72-0.94). We validated panel performance in an independent validation cohort (AUC, 0.82; 95% CI, 0.74-0.88). Our risk-stratification model was more accurate than the panel and an independent predictor for identification of LNM (AUC, 0.90; univariate: odds ratio [OR], 37.17; 95% CI, 4.48-308.35; P < .001; multivariate: OR, 17.28; 95% CI, 1.82-164.07; P = .013). The model limited potential overtreatment to only 18% of all patients, which is dramatically superior to pathologic features that are currently used (92%). CONCLUSIONS: A novel risk-stratification model for noninvasive identification of T1 CRC has the potential to avoid unnecessary operations for patients classified as high-risk by conventional risk-classification criteria.

11.
Hepatology ; 74(3): 1371-1383, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33725402

RESUMO

BACKGROUND AND AIMS: Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. APPROACH AND RESULTS: For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P < 0.01; and multivariate HR = 3.49, 95% CI = 1.81-6.71, P < 0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and nonrecurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. CONCLUSIONS: We report a transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.

12.
World J Surg Oncol ; 19(1): 94, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33781262

RESUMO

BACKGROUND: Frailty is an important consideration for older patients undergoing surgery. We aimed to investigate whether frailty could be a prognostic factor in patients with pancreatic ductal adenocarcinoma who underwent pancreatic resection. METHODS: One hundred and twenty patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma were enrolled. Frailty was defined as a clinical frailty scale score ≥4. Patients were divided into frailty (n = 29) and non-frailty (n=91) groups, and clinicopathological factors were compared between the two groups. RESULTS: The frailty group showed an older age, lower serum albumin concentration, lower prognostic nutritional index, larger tumor diameter, and higher rate of lymph node metastasis than the non-frailty group (p < 0.05). Neutrophil-lymphocyte ratio and modified Glasgow prognostic score tended to be higher in the frailty group. Cancer-specific and disease-free survival rates were significantly poor in the frailty group (p < 0.05). With a multivariate analysis, frailty was an independent prognostic factor of cancer-specific survival. CONCLUSIONS: Frailty can predict the prognosis of patients with pancreatic ductal adenocarcinoma who undergo pancreatic resection.


Assuntos
Carcinoma Ductal Pancreático , Fragilidade , Neoplasias Pancreáticas , Idoso , Carcinoma Ductal Pancreático/cirurgia , Humanos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Prognóstico
13.
Surg Today ; 51(6): 1022-1027, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33387025

RESUMO

PURPOSE: Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). METHODS: The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. RESULTS: Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0 µg/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30 days) developed in two patients (0.9%) and long-term VTE (30 days-3 years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). CONCLUSION: The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE.

14.
Surg Today ; 51(3): 340-349, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32754843

RESUMO

Organ liver transplantation and hepatocyte transplantation are not performed to their full potential because of donor shortage, which could be resolved by identifying new donor sources for the development of hepatocyte-like cells (HLCs). HLCs have been differentiated from some stem cell sources as alternative primary hepatocytes throughout the world; however, the currently available techniques cannot differentiate HLCs to the level of normal adult primary hepatocytes. The outstanding questions are as follows: which stem cells are the best cell sources? which protocol is the best way to differentiate them into HLCs? what is the definition of differentiated HLCs? how can we enforce the function of HLCs? what is the difference between HLCs and primary hepatocytes? what are the problems with HLC transplantation? This review summarizes the current status of HLCs, focusing on stem cell sources, the differentiation protocol for HLCs, the general characterization of HLCs, the generation of more functional HLCs, comparison with primary hepatocytes, and HLCs in cell-transplantation-based liver regeneration.


Assuntos
Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos/métodos , Técnicas Citológicas/métodos , Hepatócitos/transplante , Hepatopatias/terapia , Células-Tronco/fisiologia , Proteínas Morfogenéticas Ósseas/fisiologia , Diferenciação Celular/genética , Células Cultivadas , Técnicas de Cocultura , Fatores de Crescimento de Fibroblastos/fisiologia , Fator 4 Nuclear de Hepatócito/fisiologia , Proteínas de Homeodomínio/fisiologia , Humanos , Regeneração Hepática/fisiologia , Fatores de Transcrição SOXF/fisiologia , Fatores de Transcrição/fisiologia
15.
HPB (Oxford) ; 23(5): 739-745, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32988753

RESUMO

BACKGROUND: Anatomical resection (AR) is performed widely for hepatocellular carcinoma (HCC). However, it is controversial whether typical AR, which removes the whole feeding territory of the tumor-bearing portal branch bordered by the landmark veins, is necessary. The aim of this study was to investigate the utility of small AR, so-called cone unit resection, for small HCC. METHODS: Between 2007 and 2019, 372 hepatectomies were performed for HCC. Among them, 91 initial resections for small (<5 cm) solitary HCC were performed by typical AR (n = 44) or cone unit AR (n = 47). Propensity score matching was performed and clinicopathological features including prognosis were compared. RESULTS: At baseline, platelet count was higher, and liver function (serum albumin level) and indocyanine green retention at 15 min were better in the typical AR than cone unit AR group. There was no significant difference between the typical AR and cone unit AR group for tumor characteristics, short- and long-term outcomes. Even after propensity score matching (n = 29), the short- and long-term outcomes were also equivalent in between the two groups. CONCLUSION: There was no difference in prognosis of typical and cone unit AR. Therefore, cone unit AR is a feasible procedure for small HCC.

16.
Ann Surg Oncol ; 28(1): 439-446, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32562115

RESUMO

BACKGROUND: The concept of frailty becomes important for patients who undergo surgery in this recent aging society. The aim of this study is to investigate the frailty as a prognostic factor in elderly patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. PATIENTS AND METHODS: A total of 92 patients over 75 years old who underwent hepatectomy were enrolled in this study. Frailty was defined as clinical frailty scale (CFS) ≥ 4. Patients were divided into two groups, i.e., frailty group (n = 21) and no-frailty group (n = 71), and clinicopathological features were compared between them. RESULTS: The frailty group showed significant higher PIVKA-II level and larger tumor diameter (p < 0.05). CRP level and modified Glasgow prognostic score were significantly higher in the frailty group (p < 0.05). The frailty group showed higher rate of postoperative complications of Clavien-Dindo III (p = 0.06) and longer postoperative stay (p = 0.08). Cancer-specific, overall, and disease-free survival rates were significantly worse in the frailty group (p < 0.05). Frailty was detected as an independent prognostic factor on multivariate analysis of cancer-specific survival. CONCLUSION: Frailty can estimate the prognosis of HCC patients who underwent hepatectomy.


Assuntos
Carcinoma Hepatocelular , Fragilidade , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/cirurgia , Idoso Fragilizado , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Prognóstico
17.
Am Surg ; : 3134820984872, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33382339

RESUMO

BACKGROUND: Right hepatic vein sometimes could not be a reliable landmark between the anterior and posterior segment. The aim of this study was to clarify the portal perfusion area of the anterior segment and to propose a less invasive hepatectomy based on both the portal perfusion and the hepatic venous drainage. METHODS: Three-dimensional computerized tomography images of 66 patients were constructed. A case, in which the perfusion area of the anterior segment crossed over superior right hepatic vein (SRHV), was called as SRHV-inclusion. It was defined as inclusion of more than 1 cm of the proximal site of SRHV surrounded by the portal perfusion area of the anterior segment. RESULTS: SRHV-inclusion was observed in 26%. The cases with large inferior right hepatic vein (IRHV) had more frequent SRHV-inclusion (47%). The elderly patient with hepatic disorder, who had hepatocellular carcinoma near the root of the SRHV, underwent a less invasive hepatectomy (anterior segment + SRHV drainage area) resulting in the preservation of the IRHV. CONCLUSIONS: The perfusion area of the anterior segment crossed over SRHV in one fourth of patients in the study. Our proposed less invasive hepatectomy based on a hybrid concept might be an alternative operative procedure other than right hepatectomy.

18.
Ann Gastroenterol Surg ; 4(5): 591-596, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33005854

RESUMO

Aim: Pancreatectomy causes both hyperglycemia, secondary to surgical stress, and pancreatic diabetes, which leads to difficult-to-control postoperative blood glucose levels. We investigated whether using an artificial pancreas perioperatively to provide appropriate blood glucose control could reduce postoperative complications following pancreatectomy. Methods: We retrospectively enrolled 52 patients who underwent pancreatectomy at Tokushima University Hospital from 2015 to 2019. The most recent 26/52 patients received perioperative blood glucose control using an artificial pancreas. Postoperative blood glucose control with manual insulin injections based on a sliding scale was performed in the earlier 26 patients (controls). We compared surgical outcomes between the artificial pancreas group and the control group. Results: There was no significant difference in patients' white blood cell or neutrophil counts, prognostic nutritional index, neutrophil-lymphocyte ratio, and C-reactive protein-to-albumin ratio on postoperative day 1; however, lymphocyte counts were higher in the artificial pancreas group. The number of serious complications of Clavien-Dindo grade >IIIa was significantly lower in the artificial pancreas group (P < .05). Conclusions: Using an artificial pancreas for perioperative blood glucose control in patients undergoing pancreatectomy decreased the number of serious complications through proper management of blood glucose levels without hypoglycemia, and may influence peripheral lymphocytes.

19.
World J Surg Oncol ; 18(1): 241, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895059

RESUMO

BACKGROUND: The role of hypoxia-inducible factor-1α (HIF-1α) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1α expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). METHODS: Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1α expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1α expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. RESULTS: Activated HSCs induced HIF-1α mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1α expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1α expression in primary CRC. However, HIF-1α expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1α positive expression in liver metastasis had poor prognosis. CONCLUSION: HIF-1α expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Prognóstico
20.
Cell Transplant ; 29: 963689720954798, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32878465

RESUMO

The aim of our study is to determine whether insulin-producing cells (IPCs) differentiated from adipose-tissue-derived stem cells (ADSCs) can be cryopreserved. Human ADSCs were differentiated into IPCs using our two-step protocol encompassing a three-dimensional culture and xenoantigen-free method. Thereafter, IPCs were frozen using three different methods. First, IPCs were immediately frozen at -80°C (-80°C group). Second, IPCs were initially placed into a Bicell freezing container before freezing at -80°C (BICELL group). Third, a vitrification method for oocytes and embryos was used (CRYOTOP group). Cell counting kit-8 (CCK-8) assay showed that cell viability was decreased in all groups after cryopreservation (P < 0.01). Corroboratively, the amount of adenosine triphosphate was markedly decreased after cryopreservation in all groups (P < 0.01). Immunofluorescence staining showed a reduced positive staining area for insulin in all cryopreservation groups. Furthermore, 4',6-diamidino-2-phenylindole and merged immunofluorescence images showed that cryopreserved cells appeared to be randomly reduced in the -80°C group and CRYOTOP group, while only the central region was visibly reduced in the BICELL group. Using immunohistochemical staining, IPCs after cryopreservation were shown to be positive for cleaved caspase-3 antibody in all groups. Finally, insulin secretion following glucose stimulation was significantly reduced in IPCs from all groups after cryopreservation (P < 0.01). In conclusion, IPCs may be too fragile for cryopreservation with accomplished methods and further investigations for a suitable preservation method are required.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular , Criopreservação , Células Secretoras de Insulina/citologia , Células-Tronco/citologia , Trifosfato de Adenosina/metabolismo , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ditizona , Glucose/farmacologia , Humanos , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Coloração e Rotulagem , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo
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