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1.
Anticancer Res ; 41(11): 5651-5656, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732438

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the risk factors of surgical site infection (SSI) in patients who underwent liver resection for colorectal liver metastases (CRLM). PATIENTS AND METHODS: A total of 151 patients who underwent liver resection for CRLM were included in this study. We investigated the relationship between the patient characteristics and perioperative factors and the incidence of SSI. RESULTS: Nineteen (13%) of these patients developed SSI. Multivariate analysis revealed that modified Glasgow Prognostic Score (mGPS) (1 or 2, odds ratio 3.86, p=0.03) and presence of an enterostomy (yes, odds ratio 3.93, p=0.04) were significant and independent risk factors for SSI. CONCLUSION: A higher mGPS and an enterostomy were risk factors for SSI in patients who underwent a liver resection for CRLM.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Idoso , Bases de Dados Factuais , Enterostomia/efeitos adversos , Feminino , Humanos , Incidência , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/prevenção & controle , Fatores de Tempo , Tóquio/epidemiologia , Resultado do Tratamento
2.
Ann Gastroenterol Surg ; 5(4): 538-552, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34337303

RESUMO

Background: Prognostic factors after treatment for intrahepatic recurrent hepatocellular carcinoma (RHCC) after hepatic resection (Hx) are controversial. The current study aimed to examine the impact of treatment modality on the prognosis of intrahepatic RHCC following Hx. Methods: For control of variables, the subjects were 56 patients who underwent treatment for intrahepatic RHCC, three or fewer tumors, each measuring ≤3 cm in diameter without macroscopic vascular invasion (MVI), between 2000 and 2011. Retreatment consisted of repeat Hx (n = 23), local ablation therapy (n = 11) and transarterial chemoembolization or transcatheter arterial infusion (TACE/TAI) (n = 22). We retrospectively investigated the relation between type of treatment for RHCC and overall survival (OS) as well as disease-free survival (DFS). Results: In multivariate (MV) analysis, the poor prognostic factors in DFS after retreatment consisted of disease-free interval (DFI) (≤1.5 y) (P = .011), type of retreatment (TACE/TAI) (P = .002), age (<65 y old) (P = .0022), perioperative RBC transfusion (P = .025), while those in OS after retreatment were DFI (≤1.5 y) (P < .0001). In evaluation of stratification for type of retreatment, DFS in the repeat Hx group was significantly better than those in the local ablation therapy group or the TACE/TAI group (P = .023 or P < .0001, respectively). Conclusions: DFI (≤1.5 y) was an independent poor prognostic factor in both DFS and OS, and repeat Hx for intrahepatic RHCC, few in number and size without MVI, seems to achieve the most reliable local control.

3.
Pancreas ; 50(3): 313-316, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835961

RESUMO

OBJECTIVES: The aim of this study was to clarify the effectiveness of combination chemotherapy targeting gemcitabine (GEM)-induced nuclear factor kappa B as adjuvant therapy for pancreatic cancer. METHODS: Patients who were planned after curative surgery (residual tumor classification R0 or R1) for pancreatic cancer to receive six cycles of adjuvant chemotherapy of regional arterial infusion of nafamostat mesilate with GEM between June 2011 and April 2017 were enrolled in this single-center, institutional review board-approved phase II trial (UMIN000006163). The Kaplan-Meier method was used to estimate disease-free survival and overall survival. RESULTS: In 32 patients [male/female: 18/14; age: median, 65.5 years (range, 48-77 years); pathological stage (Union for International Cancer Control 8th): IA/IB/IIA/IIB/III, 2/2/9/18/1, respectively] who met the eligibility criteria, the median overall survival and disease-free survival were 36.4 months (95% confidence interval, 31.7-48.3) and 16.4 months (95% confidence interval, 14.3-22.0), respectively. Grade 4 treatment-related hematological toxicities were seen in 5 patients (15.6%) (all neutropenia). One patient developed grade 3 nonhematological toxicities (rash). CONCLUSIONS: Adjuvant chemotherapy with regional arterial infusion of nafamostat mesilate and GEM is safe and has potential as an option in adjuvant setting after curative surgery for pancreatic cancer.

4.
Anticancer Res ; 41(4): 2171-2175, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813429

RESUMO

BACKGROUND: Although indications of laparoscopic hepatectomy have been expanded, the laparoscopic approach after right hepatic lobectomy has a very high burden. The purpose of this study was to evaluate patients undergoing laparoscopic repeat hepatectomy for recurrent hepatic tumors after open right lobectomy. PATIENTS AND METHODS: Five cases of laparoscopic repeat hepatectomy for recurrent hepatic tumors after open right lobectomy were included in the study. RESULTS: All the tumors in segment 3 were intraoperatively detected and curatively resected by partial hepatectomy. The tumors in segment 2 could not be detected intraoperatively due to hypertrophic liver deformity and adhesion. They were curatively resected by anatomical subsegmental approach. CONCLUSION: For recurrent tumors located in segment 2 after right lobectomy, anatomical subsegmental approach should be preferred, not only from an oncological standpoint, but also for securing curative laparoscopic resection and overcoming anatomical difficulties.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Reoperação/métodos , Idoso , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Indução de Remissão/métodos , Resultado do Tratamento
5.
Surg Endosc ; 35(9): 5375-5380, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33913029

RESUMO

It has been known that repeat laparoscopic hepatectomy (RLH) after open hepatectomy is technically challenging because of adhesions around the hilum. It is quite often that conventional tourniquet technique for the Pringle maneuver is difficult in RLH, and we introduced Laparoscopic Satinsky Vascular Clamp (LSVC) for inflow control in RLH. The Spiegel lobe is the anatomical landmark in LSVC technique. If a space behind the hepatoduodenal ligament and the Spiegel lobe was obtained, LSVC was applied laterally from the left side of the hepatoduodenal ligament, whereas LSVC was vertically applied for those with obstruction of a space behind the hepatoduodenal ligament. We performed 14 cases of RLH for those with histories of open hepatectomies by lateral (n = 6) and vertical (n = 8) LSVC technique with successful inflow control, confirmed by intraoperative Doppler ultrasound. Five patients underwent 2 or more previous histories of hepatectomies. The RLH included segmentectomy (n = 1), subsegmentectomy (n = 2) and partial hepatectomy (n = 11). The median time for the Pringle maneuver, operative time, and blood loss was 47 min, 237.5 min, and 160 mL. All the patients completed pure laparoscopic hepatectomy. In conclusion, LSVC technique is a safe and reliable technique for the Pringle maneuver in RLH.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Duração da Cirurgia
6.
In Vivo ; 35(2): 1271-1276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622930

RESUMO

BACKGROUND/AIM: Useful prophylaxes of chyle leak (CL) after pancreatic surgery have not been established. The aim of the study was to identify an early clinical predictor for CL. PATIENTS AND METHODS: Fifty-five patients who underwent subtotal stomach preserved pancreaticoduodenectomy (SSPPD) were included. Clinical factors associated with postoperative CL were evaluated. RESULTS: Eleven patients (20%) developed a CL after SSPPD. Shorter operative time, absent pancreatic fistula, and triglyceride output volume at postoperative day (POD) two were independent risk factors for CL. The receiver operating characteristics curve of the daily triglyceride output volume at POD two indicated a cut-off point of 177 mg (AUC=0.782; p=0.004; 95% CI=0.639-0.925). CL was significantly associated with prolonged postoperative hospital stay in patients who did not develop a pancreatic fistula (p=0.003). CONCLUSION: Daily triglyceride output volume of >177 mg at POD two may be a predictor of CL following pancreaticoduodenectomy.


Assuntos
Quilo , Pancreaticoduodenectomia , Drenagem , Humanos , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos
7.
Pancreatology ; 21(1): 299-305, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33214083

RESUMO

INTRODUCTION: A soft remnant texture of the pancreas is commonly accepted as a risk factor for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). However, its assessment is subjective. The aim of this study was to evaluate the significance of intraoperative amylase level of the pancreatic juice as a risk factor of POPF after PD. METHOD: This study included 75 patients who underwent PD between November 2014 and April 2020 at Jikei University Hospital. We investigated the relationship between pancreatic texture, intraoperative amylase level of pancreatic juice, results of the pathological evaluations, and the incidence of POPF. RESULTS: Twenty-three patients (31%) developed POPF. The significant predictors of POPF were non-ductal adenocarcinoma (p < 0.01), soft pancreatic remnant (p < 0.01), high intraoperative blood loss (p < 0.01), high intraoperative amylase level of pancreatic juice (p < 0.01), and low pancreatic fibrosis (p < 0.01). Multivariate analysis revealed that the significant independent predictors of POPF were high intraoperative blood loss (p < 0.01) and high intraoperative amylase level of pancreatic juice (p = 0.02). Receiver operating characteristic (ROC) analysis showed that the cut-off value for the intraoperative amylase level of pancreatic juice was 2.17 × 105 IU/L (area under the curve = 0.726, sensitivity = 95.7%, and specificity = 50.0%) CONCLUSIONS: The intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD.

8.
Transl Lung Cancer Res ; 9(5): 2255-2276, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209648

RESUMO

The emergence of whole slide imaging technology allows for pathology diagnosis on a computer screen. The applications of digital pathology are expanding, from supporting remote institutes suffering from a shortage of pathologists to routine use in daily diagnosis including that of lung cancer. Through practice and research large archival databases of digital pathology images have been developed that will facilitate the development of artificial intelligence (AI) methods for image analysis. Currently, several AI applications have been reported in the field of lung cancer; these include the segmentation of carcinoma foci, detection of lymph node metastasis, counting of tumor cells, and prediction of gene mutations. Although the integration of AI algorithms into clinical practice remains a significant challenge, we have implemented tumor cell count for genetic analysis, a helpful application for routine use. Our experience suggests that pathologists often overestimate the contents of tumor cells, and the use of AI-based analysis increases the accuracy and makes the tasks less tedious. However, there are several difficulties encountered in the practical use of AI in clinical diagnosis. These include the lack of sufficient annotated data for the development and validation of AI systems, the explainability of black box AI models, such as those based on deep learning that offer the most promising performance, and the difficulty in defining the ground truth data for training and validation owing to inherent ambiguity in most applications. All of these together present significant challenges in the development and clinical translation of AI methods in the practice of pathology. Additional research on these problems will help in resolving the barriers to the clinical use of AI. Helping pathologists in developing knowledge of the working and limitations of AI will benefit the use of AI in both diagnostics and research.

9.
Int J Surg Case Rep ; 71: 319-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492643

RESUMO

INTRODUCTION: The prognosis of atypical pulmonary carcinoid with liver metastases is extremely poor, and patients with multiple liver metastases are often treated using non-surgical therapies. We report a case with multiple liver metastases from atypical pulmonary carcinoid that was successfully treated using two-stage hepatectomy combined with embolization of portal vein branches. PRESENTATION OF CASE: A 48-year-old man was referred to our department after multiple liver tumors were detected in both liver lobes on computed tomography. He had undergone right upper lobectomy of the lung for atypical pulmonary carcinoid (T2a, N0, M0; Stage IB) 2 years previously. Positron emission tomography-computed tomography showed no extrahepatic tumor manifestations. The tumors were located in segment 2, 3, 5/8 and the right hepatic vein drainage area. We planned complete resection of metastases in a two-stage hepatectomy. The first stage comprised concomitant left lateral segmentectomy, partial hepatectomy of segment 5/8 and portal vein embolization of the posterior segmental branches. The second stage comprised resection of the right hepatic vein drainage area, performed 21 days after the first surgery. Histopathological diagnosis was liver metastases of atypical pulmonary carcinoid. Postoperative bile leak developed, which was treated with endoscopic retrograde biliary drainage and percutaneous bile leak drainage. He has been followed for 24 months postoperatively without tumor recurrence. DISCUSSION: Two-stage hepatectomy may represent an option for bilobar multiple liver metastases from atypical pulmonary carcinoid. CONCLUSION: We successfully treated a patient with multiple liver metastases of atypical pulmonary carcinoid using a two-stage hepatectomy combined with portal vein embolization of the posterior segmental branches.

10.
J Clin Biochem Nutr ; 66(2): 116-123, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32231407

RESUMO

Glutathione peroxidase 4 (GPx4) is a unique antioxidant enzyme that directly reduces the phospholipid hydroperoxides (PLOOH) generated in biomembranes using glutathione as the reductant. We have previously reported that the Caenorhabditis elegans gpx-quad mutant, which lacks all homologous genes of GPx4 has a reduced lifespan compared with the wild-type. However, the mechanisms underlying the lifespan reduction remain unclear. By monitoring the change in PLOOH production with age, we found that PLOOH was elevated in the gpx-quad mutants compared with the wild-type during the reproductive period. Administration of vitamin E not only reduced the PLOOH content but also prolonged the lifespan of the gpx-quad mutants. In contrast, vitamin C did not extend the lifespan of the gpx-quad mutants. Interestingly, we found that the inhibition of lipid peroxidation by vitamin E during 5 to 10 days after hatching is important to extend the lifespan of C. elegans. These results suggest that production of PLOOH during the reproductive period strongly influences the lifespan of C. elegans.

11.
Case Rep Gastroenterol ; 14(1): 56-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110201

RESUMO

Hepatic epithelioid hemangioendothelioma (EHE) is extremely rare, and preoperative diagnosis is difficult because hepatic EHE has clinicopathological features that are similar to those of angiosarcoma. However, it is important to differentiate hepatic EHE from angiosarcoma because the latter is an aggressive tumor with poor prognosis. We herein report a case of hepatic EHE that was difficult to distinguish from angiosarcoma by tumor biopsy. A 30-year-old man with Crohn's disease presented with multiple liver tumors. The tumors were preoperatively diagnosed as angiosarcoma by tumor biopsy. The patient underwent extended left hemihepatectomy with biliary reconstruction and partial resection of segments 6 and 8. Immunohistochemical staining was positive for CD34, factor VIII, and calmodulin binding transcription activator 1 (CAMTA1), and the pathological diagnosis was EHE. Two years after surgery, a recurrent tumor was found in liver segment 6, for which laparoscopic partial hepatectomy was performed. Pathological examination revealed recurrence of EHE. The patient remained well with no evidence of tumor recurrence as of 9 months after the second resection. In conclusion, we described a case of hepatic EHE that was initially diagnosed as angiosarcoma on biopsy. Immunohistochemical staining with CAMTA1 may help distinguish EHE from angiosarcoma.

12.
Anticancer Res ; 39(11): 6325-6332, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704863

RESUMO

BACKGROUND/AIM: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older. PATIENTS AND METHODS: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or older; n=16). RESULTS: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence. CONCLUSION: Hepatic resection for HCC and CRLM in patients aged 80 years and older may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and older, hepatic resection may be effective when negative surgical margins can be achieved.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Comorbidade , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Margens de Excisão , Complicações Pós-Operatórias , Análise de Sobrevida , Resultado do Tratamento
13.
Int Cancer Conf J ; 8(4): 190-194, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31559121

RESUMO

Breast cancer is known to metastasize to all organs of the body. However, abdominal lymph node metastases from breast cancer are extremely rare. We herein report a resected case of an invasive pancreatic ductal adenocarcinoma (PDAC) in which abdominal lymph node metastases from breast cancer were diagnosed. A 54-year-old woman was pointed out to have a tumor in the pancreatic tail with dilatation of the distal pancreatic duct. She had undergone partial mastectomy for left breast cancer at the age of 51 years and had undergone partial liver resection for liver metastasis in the segment 3/4 6 months earlier. Computed tomography revealed a low-density tumor in the pancreatic tail with dilated distal main pancreatic duct. Magnetic resonance imaging (MRI) exhibited a high-intensity tumor in the pancreatic tail in diffusion-weighted images. With a diagnosis of pancreatic cancer, distal pancreatectomy and splenectomy with lymph nodes dissection was performed. Lymph node metastases along the splenic artery were pathologically similar to PDAC. However, lymph node metastases along the left gastric artery, common hepatic artery, celiac axis, and superior mesenteric artery were pathologically similar to breast cancer. Immunohistochemistry staining of abdominal lymph nodes with GATA-3 was positive, which strongly suggested metastatic breast cancer. Although she received chemotherapy with S-1 for breast cancer and PDAC for 4 months, MRI showed multiple liver metastases derived from breast cancer. Finally, she died 12 months after operation.

14.
J Immunol ; 203(8): 2076-2087, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31534007

RESUMO

The imbalanced redox status in lung has been widely implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. To regulate redox status, hydrogen peroxide must be adequately reduced to water by glutathione peroxidases (GPx). Among GPx isoforms, GPx4 is a unique antioxidant enzyme that can directly reduce phospholipid hydroperoxide. Increased lipid peroxidation products have been demonstrated in IPF lungs, suggesting the participation of imbalanced lipid peroxidation in IPF pathogenesis, which can be modulated by GPx4. In this study, we sought to examine the involvement of GPx4-modulated lipid peroxidation in regulating TGF-ß-induced myofibroblast differentiation. Bleomycin-induced lung fibrosis development in mouse models with genetic manipulation of GPx4 were examined. Immunohistochemical evaluations for GPx4 and lipid peroxidation were performed in IPF lung tissues. Immunohistochemical evaluations showed reduced GPx4 expression levels accompanied by increased 4-hydroxy-2-nonenal in fibroblastic focus in IPF lungs. TGF-ß-induced myofibroblast differentiation was enhanced by GPx4 knockdown with concomitantly enhanced lipid peroxidation and SMAD2/SMAD3 signaling. Heterozygous GPx4-deficient mice showed enhancement of bleomycin-induced lung fibrosis, which was attenuated in GPx4-transgenic mice in association with lipid peroxidation and SMAD signaling. Regulating lipid peroxidation by Trolox showed efficient attenuation of bleomycin-induced lung fibrosis development. These findings suggest that increased lipid peroxidation resulting from reduced GPx4 expression levels may be causally associated with lung fibrosis development through enhanced TGF-ß signaling linked to myofibroblast accumulation of fibroblastic focus formation during IPF pathogenesis. It is likely that regulating lipid peroxidation caused by reduced GPx4 can be a promising target for an antifibrotic modality of treatment for IPF.


Assuntos
Fibrose Pulmonar Idiopática/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Animais , Bleomicina , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/patologia , Peroxidação de Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Miofibroblastos/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/deficiência , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Fator de Crescimento Transformador beta/metabolismo
15.
Anticancer Res ; 39(9): 5143-5148, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519626

RESUMO

BACKGROUND/AIM: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older. PATIENTS AND METHODS: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or over; n=16). RESULTS: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence. CONCLUSION: Hepatic resection for HCC and CRLM in patients aged 80 years and over may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and over, hepatic resection may be effective when negative surgical margins can be achieved.


Assuntos
Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Resultado do Tratamento
16.
Nat Commun ; 10(1): 3145, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316058

RESUMO

Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions. Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis. Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity. Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells. NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment. CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD. These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD.


Assuntos
Ferroptose , Doença Pulmonar Obstrutiva Crônica/patologia , Fumar , Animais , Células Epiteliais/patologia , Humanos , Ferro/metabolismo , Peroxidação de Lipídeos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Coativadores de Receptor Nuclear/genética , Fosfolipídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Case Rep Gastroenterol ; 13(2): 258-264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275089

RESUMO

Pulmonary embolism (PE) is a rare but potentially fatal complication that may develop in a living liver donor. Here, we report a case of non-massive PE diagnosed by elevated serum D-dimer levels and successfully treated using anticoagulant therapy. A 57-year-old man underwent extended left hepatectomy as a living liver donor. His past medical history included hypertension and dyslipidemia which required medication and a history of smoking. Mechanical prophylactic measures for venous thromboembolism, including intermittent pneumatic compression and elastic stocking, were used; however, no pharmacological prophylaxis was used. Although the patient ambulated on postoperative day (POD) 1, he developed hypoxia. Serum D-dimer level was elevated to 29.3 ng/mL on POD 2. Enhanced computed tomography revealed small peripheral PEs in the branches of the right upper, right middle, and left lower lobes without deep vein thrombosis. Intravenous heparin was initiated followed by warfarin. The thrombi resolved completely by POD 13, following which warfarin was continued for 3 months. As of 25 months after donation, the patient remains well without recurrence of PE. Early diagnosis and treatment of postoperative PE are critical for preventing mortality of liver donors.

18.
Cell Death Dis ; 10(6): 449, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31209199

RESUMO

Nonalcoholic steatohepatitis (NASH) is a metabolic liver disease that progresses from simple steatosis to the disease state of inflammation and fibrosis. Previous studies suggest that apoptosis and necroptosis may contribute to the pathogenesis of NASH, based on several murine models. However, the mechanisms underlying the transition of simple steatosis to steatohepatitis remain unclear, because it is difficult to identify when and where such cell deaths begin to occur in the pathophysiological process of NASH. In the present study, our aim is to investigate which type of cell death plays a role as the trigger for initiating inflammation in fatty liver. By establishing a simple method of discriminating between apoptosis and necrosis in the liver, we found that necrosis occurred prior to apoptosis at the onset of steatohepatitis in the choline-deficient, ethionine-supplemented (CDE) diet model. To further investigate what type of necrosis is involved in the initial necrotic cell death, we examined the effect of necroptosis and ferroptosis inhibition by administering inhibitors to wild-type mice in the CDE diet model. In addition, necroptosis was evaluated using mixed lineage kinase domain-like protein (MLKL) knockout mice, which is lacking in a terminal executor of necroptosis. Consequently, necroptosis inhibition failed to block the onset of necrotic cell death, while ferroptosis inhibition protected hepatocytes from necrotic death almost completely, and suppressed the subsequent infiltration of immune cells and inflammatory reaction. Furthermore, the amount of oxidized phosphatidylethanolamine, which is involved in ferroptosis pathway, was increased in the liver sample of the CDE diet-fed mice. These findings suggest that hepatic ferroptosis plays an important role as the trigger for initiating inflammation in steatohepatitis and may be a therapeutic target for preventing the onset of steatohepatitis.


Assuntos
Ferroptose , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Cromanos/farmacologia , Citocinas/metabolismo , Dieta , Etionina , Ferroptose/efeitos dos fármacos , Hepatite/imunologia , Hepatite/metabolismo , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Quelantes de Ferro/farmacologia , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Necroptose/efeitos dos fármacos , Necrose , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo
19.
Surg Case Rep ; 5(1): 103, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236705

RESUMO

BACKGROUND: Metastatic biliary tract cancer (BTC) has poor prognosis. Recently, patients with metastatic BTC who respond well to systemic chemotherapy can be treated by radical resection or "conversion surgery." CASE PRESENTATION: A 67-year-old male patient was diagnosed with intrahepatic cholangiocarcinoma with para-aortic metastases [cT2N1M1, stage IVB]. He was enrolled in our phase II study for unresectable BTC consisting of cisplatin (25 mg/m2 i.v. for 30 min) followed by gemcitabine (1000 mg/m2 i.v. for 30 min) on days 1 and 8 and oral S-1 on alternate days. After 8 courses of this regimen, marked regression of para-aortic lymph metastases was achieved, and we performed extended left hepatic lobectomy with the caudate lobe, concomitant portal vein resection, and lymph node dissection including the para-aortic region. The patient made a satisfactory recovery and was discharged on postoperative day 25. Histopathological examination revealed more than 50% of the tumor area replaced with fibrosis, and curative resection was achieved (ypT2N1M1, stage IVB, Evans criteria IIb). The patient received adjuvant chemotherapy using S-1 for 12 months and remains well with no evidence of tumor recurrence as of 48 months after surgery. CONCLUSIONS: We herein report a successfully treated case of advanced BTC with para-aortic lymph node metastases by conversion surgery after combination chemotherapy using gemcitabine, cisplatin, and S-1.

20.
Anticancer Res ; 39(3): 1469-1478, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842184

RESUMO

BACKGROUND/AIM: Prediction of local recurrence and distant metastasis is important for patients with pancreatic cancer following pancreatic resection. The aims of this study were to identify a novel prognostic score which combines distance from common hepatic artery (CHA) or superior mesenteric artery (SMA) and examine serum CA19-9 for predicting local recurrence in patients with pancreatic cancer following resection. PATIENTS AND METHODS: This retrospective study comprised 149 patients who went through elective pancreatic resection for pancreatic cancer between June 2007 and December, 2017. We established new scores (CHA score and SMA score) using the distance between CHA or SMA and the tumor measured by preoperative CT scan in combination with preoperative serum CA19-9 values. We evaluated the relationship between the scores and local recurrence of pancreatic cancer. Finally, we investigated the relationship between the scores and local recurrence-free survival as well as the overall survival. RESULTS: The optimal cut-off levels of the distance between CHA or SMA and the tumor, as determined by ROC analysis, were 20.55 and 10.9 mm, respectively. In a logistic progression model, demonstrated by multivariate analysis, lymphatic invasion (p=0.002), preoperative serum CA19-9 (p=0.007) and SMA score (p=0.004) were identified to be independent predictors of local recurrence in patients with pancreatic cancer following resection. In a Cox progression model, demonstrated by multivariate analysis, intraoperative blood loss (p=0.022), lymphatic invasion (p=0.001) and SMA score (p<0.001) were identified as independent factors of local recurrence. The independent predictors of poor overall survival by multivariate analysis consisted of intraoperative blood loss (p=0.045), intraoperative transfusion (p=0.026) and SMA score (p<0.001). CONCLUSION: The SMA score may be an independent preoperative predictor of local recurrence and prognosis in patients with pancreatic cancer.


Assuntos
Antígeno CA-19-9/sangue , Artéria Mesentérica Superior/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Pancreáticas , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Tomografia Computadorizada por Raios X , Ultrassonografia
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