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1.
Cancer Invest ; 40(1): 81-89, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34236269

RESUMO

The aim of the current study was to investigate the efficacy and safety of sorafenib and intermittent hepatic arterial infusion chemotherapy with cisplatin for unresectable hepatocellular carcinoma (HCC) with severe portal vein invasion. The antitumor effect was a complete response in 1 of 38 patients, a partial response in 12 patients, stable disease in 16 patients, and progressive disease in 9 patients, for a 34.2% response rate and a 76.3% disease control rate. This regimen had favorable efficacy and acceptable safety and may be feasible for unresectable HCC with severe portal vein invasion.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Idoso , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Estudos Prospectivos , Sorafenibe/farmacologia
2.
World J Surg ; 46(3): 542-549, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34773134

RESUMO

BACKGROUND: Various tubes may be fixed to the skin by ligation using silk sutures after gastrointestinal surgery. We investigated the effects of a skin substitute, "Nonaht®," on pain and skin inflammation at the fixation sites of various tubes. METHODS: The effects of tubes (abdominal drains, small intestinal feeding tubes, and bile duct drainage tubes) fixed in place using either silk sutures or Nonaht were compared for 1-3 months. RESULTS: The median pain scores at the fixation site when abdominal drains were removed were 1.0 with silk sutures and 0 with Nonaht (p < 0.001). Scarring at the fixation site at postoperative month (POM) 1 occurred in 13 of 28 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). The median pain scores at the fixation site with long-term tubes on postoperative day (POD) 14 and POM 1 were 2.0 and 1.0, respectively, with silk sutures, and none at all time points with Nonaht (p < 0.001). Scarring at the fixation site at POM 3 occurred in all 10 cases in the silk suture group and in no cases in the Nonaht group (p < 0.001). CONCLUSIONS: Patients with conventional skin fixation of tubes using silk sutures were continuously aware of pain at the fixation site and developed skin damage and subsequent scar formation, especially for tubes inserted for ≥ 1 month. The use of Nonaht may reduce the incidence of dermatitis and wound infections at tube fixation sites, thereby promoting early postoperative recovery.


Assuntos
Drenagem , Suturas , Humanos , Projetos Piloto , Estudos Prospectivos , Técnicas de Sutura
3.
HPB (Oxford) ; 24(1): 101-115, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34244053

RESUMO

BACKGROUND: We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy. METHODS: Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin × Lymphocyte)/(CRP × 104). Patients with a CALLY index ≥5 (n = 200) were compared to those with an index <5 (n = 184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort). RESULTS: The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p = 0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5: 71% vs. <5: 46%; p < 0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p < 0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort. CONCLUSION: The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Proteína C-Reativa , Hepatectomia/efeitos adversos , Humanos , Linfócitos , Prognóstico , Estudos Retrospectivos
4.
Cancer Invest ; 35(4): 271-276, 2017 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-28272913

RESUMO

OBJECTIVES: We conducted a phase I study of sorafenib and intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable hepatocellular carcinoma. METHODS: Sorafenib was administered continuously, whereas cisplatin was administered once every 3 weeks. We estimated the safety and efficacy. RESULTS: Fifteen patients were enrolled into this study. The dose-limiting toxicities occurred at sorafenib 800 mg and cisplatin 20 mg/m2. The recommended dose was at sorafenib 400 mg and cisplatin 30 mg/m2. The disease control rate was 73.3%. CONCLUSIONS: This treatment is feasible for unresectable hepatocellular carcinoma. Further evaluation of the regimen in a randomized controlled trial is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Esquema de Medicação , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Masculino , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Sorafenibe
5.
Nihon Geka Gakkai Zasshi ; 116(4): 243-8, 2015 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-26422887

RESUMO

Pain is a sensation associated with subjective factors, making it difficult to measure and assess. Currently, there is no widely accepted method of objectively assessing pain, and therefore subjective assessments such as the Visual Analogue Scale (VAS) are generally used. The PainVision system has been developed for the quantitative analysis of pain and comparison of postoperative pain intensity. In this study, we investigated whether postoperative pain could be objectively assessed using this system in digestive tract surgery patients. Pain scores were measured with the VAS, the PainVision system, and the short-form McGill Pain Questionnaire in patients undergoing open or laparoscopic hepatectomy, open or laparoscopic gastrectomy, and laparoscopic cholecystectomy. As measured using the PainVision system, postoperative pain intensity was lower in patients who underwent laparoscopic surgery compared with open hepatectomy. In open hepatectomy patients, pain intensity measured by the PainVision system was significantly lower on postoperative days (POD) 7 and 10 than on POD 1. Preemptive use of nonsteroidal antiinflammatory drugs significantly reduced postoperative pain in open hepatectomy patients. The results showed that PainVision effectively quantifies pain intensity after digestive tract surgery. Objective assessment of postoperative pain may lead to earlier mobility and improved quality of life.


Assuntos
Trato Gastrointestinal/cirurgia , Dor Pós-Operatória/diagnóstico , Hepatectomia , Humanos , Laparoscopia , Medição da Dor , Inquéritos e Questionários
6.
Gan To Kagaku Ryoho ; 41(12): 1494-6, 2014 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-25731230

RESUMO

We report a novel technique of laparoscopic hepatectomy (lap-HT) performed at our hospital and the outcomes.Lap -HT was performed in 90 cases at our hospital, including 38 cases of anatomical resection of the liver.After mobilization of the right lobe with the patient in the half-lateral position, we resected the liver tissue using cavitron ultrasonic surgical aspirator (CUSA) and AquamantysTM Bipolar®.This surgical instrument is useful for laparoscopic anatomical resection of the liver because it is based on vessel sealing technology.In the 90 cases in which lap-HT was performed, the mean duration of surgery and mean blood loss were 332.9 minutes and 381 mL, respectively. The mean duration of hospitalization after surgery was 12.1 days, and postoperative complications were noted in 5 cases(5.6%). Comparison of the clinical factors and short-term performance of the surgery between liver cirrhosis patients who underwent open hepatectomy and lap-HT revealed that blood loss was significantly lower and the hospital stay duration was significantly shorter in patients who underwent lap-HT. Our findings suggest that laparoscopic anatomical resection of the liver can be safely performed using this novel technique and surgical instrument.


Assuntos
Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Idoso , Perda Sanguínea Cirúrgica , Feminino , Humanos , Tempo de Internação , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Oncol Lett ; 27(3): 124, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38348389

RESUMO

Sarcomatoid hepatocellular carcinoma (SHCC) is a rare and highly lethal subtype of HCC. The present study aimed to explore the unique markers of SHCC using whole gene expression analysis. Subsequently, gene expression analysis was performed using five sarcomatoid and seven carcinomatoid components of seven tissues from patients with SHCC. The results demonstrated a significant downregulation of polybromo 1 (PBRM1) gene expression in the sarcomatoid components. Immunohistochemical staining also indicated a decreased expression of PBRM1 in the sarcomatoid components. Moreover, gene ontology enrichment analysis revealed that most of the 336 differentially expressed genes between the sarcomatoid and carcinomatoid components were involved in functions associated with DNA replication and histone methylation, which was consistent with the loss of function of PBRM1 which encodes Switch/sucrose-non-fermentable chromatin remodeling complex protein. Therefore, the results of the present study suggested that PBRM1 may be a candidate biomarker for the evaluation of SHCC.

8.
Gan To Kagaku Ryoho ; 40(12): 1678-80, 2013 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-24393886

RESUMO

A 76-year-old woman was diagnosed as having hepatocellular carcinoma( HCC), and partial hepatectomy was performed in 2007. Transarterial chemoembolization (TACE) was performed for recurrent HCCs in 2009. Ileocecal resection was performed for peritoneal dissemination of HCC localized in the ileocecal area, and sorafenib therapy was initiated in October 2009. TACE was performed for recurrent HCCs in December 2009 and March 2010. Positron emission tomography( PET) revealed a solitary intrahepatic recurrent HCC and left ovarian metastasis, and partial hepatectomy and left ovariectomy were performed in June 2010. Multiple lung metastases were detected, and systemic chemotherapy with cisplatin was initiated in February 2011. The lung metastatic tumors disappeared after 3 courses of treatment. The patient is disease free at 2 years after treatment. We encountered a case of advanced recurrent HCC is which complete response (CR) was achieved with multimodality therapy using sorafenib and surgical treatment.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Idoso , Terapia Combinada , Embolização Terapêutica , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Metástase Neoplásica , Recidiva , Indução de Remissão
9.
Asian Pac J Cancer Prev ; 24(3): 1089-1094, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36974565

RESUMO

OBJECTIVE: Liver resection in the super elderly patients remains challenging because of comorbidities and operative tolerability. METHODS: In this study, we compared postoperative complications and survival in patients aged ≥85 yr included five patients aged ≥90 yr with those aged 70-79 and 80-84 yr at a single institution. RESULTS: Three hundred sixty-seven patients aged ≥70 yr underwent liver resection and were divided into three groups based on age at operation between 2010 and 2022; (a) 70-79 yr (median of 74 yr, n=245), (b) 80-84 yr (median of 82 yr, n=81), and (c) ≥85 yr (median of 87 yr, n=41). In the ≥85 yr group (90-yr-old group), twenty-five patients (four) had hypertension, fourteen (one) had diabetes mellitus, seven (one) had cardiovascular disease, and five patients (one) had dementia. The rate of comorbidities did not differ significantly among three groups. The rate of postoperative complications (Clavien-Dindo grade 3a≤) was 25% in the 70- to 79-yr-old group, 27% in the 80- to 84-yr-old group, and 17% in the ≥85-yr-old group (20% in the ≥90-yr-old group) (N.S.). The 1- and 5-yr patient survival rates in the ≥85-yr-old group were 90.1% and 48.5% respectively, compared with 86.7% and 60.9% in the 70- to 79-yr-old group and 83.8% and 66.3% in the 80- to 84-yr-old group, respectively (N.S.). CONCLUSION: Despite the management of comorbidities, liver resection for well-selected super elderly patients, such as those aged ≥85 yr included ≥90yr, has acceptable outcomes. The age of patient is not an absolute contraindication to liver resection.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Hepatectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
10.
Cancers (Basel) ; 15(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37296868

RESUMO

BACKGROUND/PURPOSE: The effect of the ABO blood group on the survival of patients with hepatocellular carcinoma (HCC) is unclear. The aim of the present study is to determine the prognostic impact of ABO blood types on the survival of a Japanese population of patients with HCC who underwent surgical resection. METHODS: Patients with HCC (n = 480) who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed. Survival outcomes were investigated according to ABO blood type (A, B, O, or AB). Outcomes for type A (n = 173) and non-type A (n = 173) groups after surgery were compared using 1-to-1 propensity score matching to control for variables. RESULTS: In the study cohort, 173 (36.0%), 133 (27.7%), 131 (27.3%), and 43 (9.0%) of participants had Type A, O, B, and AB, respectively. Type A and non-type A patients were successfully matched based on liver function and tumor characteristics. Recurrence-free survival (RFS; hazard ratio [HR] 0.75, 95% confidence interval [Cl] 0.58-0.98, p = 0.038) and overall survival (OS; HR: 0.67, 95% Cl: 0.48-0.95, p = 0.023) for patients with blood type A were both significantly decreased relative to non-type A patients. Cox proportional hazard analysis demonstrated that patients with HCC who have blood type A had a worse prognosis than those with non-type A blood. CONCLUSION: ABO blood type may have a prognostic impact on patients with HCC after hepatectomy. Blood type A is an independent unfavorable prognostic factor for recurrence-free and overall survival (RFS and OS) after hepatectomy.

11.
Gan To Kagaku Ryoho ; 39(12): 1991-3, 2012 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-23267953

RESUMO

An 84-year-old woman experienced epigastralgia with increasing serum protein induced by vitamin K absence or antagonists -II(PIVKA-II) levels, and she was referred to our hospital. The serum levels of tumor markers were elevated[ alpha -fetoprotein(AFP) 22,640 ng/mL, PIVKA-II 35,140 mAU/mL], and a mass lesion of 7 cm in diameter in the right lobe of the liver with portal vein tumor thrombus (PVTT) in the major trunk was detected by abdominal computed tomography (CT) scan. She was diagnosed with unresectable hepatocellular carcinoma (HCC) with PVTT, and sorafenib in combination with intermittent cisplatin(CDDP) hepatic arterial infusion chemotherapy(HAIC)was performed. After 3 courses of the therapy, the serum levels of tumor markers were decreased (AFP: 16,283 ng/mL, PIVKA-II: 2,924 mAU/mL), and the size of the tumor had also decreased to 2 cm in diameter. PVTT decreased from Vp4 to Vp3. We judged that it was resectable, and extended right hepatectomy and portal vein embolectomy was performed. Complete tumor necrosis was seen during pathologic inspection of PVTT. Although she presented with refractory pleural effusion and ascites after operation, she recovered and left our hospital on postoperative day 70. No recurrences have occurred during the 6 months after the operation. Sorafenib in combination with intermittent CDDP HAIC is considered to be an effective therapy for advanced HCC with PVTT in the major trunk.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Veia Porta/patologia , Trombose Venosa/cirurgia , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/cirurgia , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Sorafenibe
12.
Gan To Kagaku Ryoho ; 39(12): 2009-11, 2012 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-23267959

RESUMO

A 55-year-old man who underwent eye enucleation at our hospital's ophthalmology department was pathologically diagnosed with malignant melanoma. Four months later after diagnosis, he underwent positron emission tomography/computed tomography for detecting systemic metastasis. Abnormal accumulation was found in S4 of the liver. He was therefore referred to the gastrointestinal department, where liver metastasis from malignant melanoma was diagnosed by biopsy. He underwent radiofrequency ablation therapy. A recurrence 3 months later was judged difficult to manage medically. He was thus sent to our department. Preoperative magnetic resonance imaging revealed multiple tumors in both liver lobes. Thus far, no treatment strategy has been established for hepatic metastases of malignant melanoma. After receiving a thorough explanation, he agreed to partial hepatectomy. We identified 14 tumors by intraoperative ultrasonography as sites for partial hepatectomy. Postoperative chemotherapy was administered. He died of hepatic failure 9 months after the operation. It is necessary to accumulate further cases on a national scale, because establishment of appropriate therapy for this condition is urgently needed.


Assuntos
Neoplasias da Coroide/patologia , Neoplasias Hepáticas/cirurgia , Melanoma/cirurgia , Neoplasias da Coroide/tratamento farmacológico , Evolução Fatal , Hepatectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Melanoma/tratamento farmacológico , Melanoma/secundário , Pessoa de Meia-Idade
13.
Gan To Kagaku Ryoho ; 39(12): 1978-81, 2012 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-23267949

RESUMO

BACKGROUND: Intravenous injection of the indocyanine green (ICG) reagent was performed as a liver function test 1 to 2 weeks prior to surgery. ICG fluorescent imaging was performed using the Photodynamic Eye (PDE) infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). METHODS: Intravenous injection of the ICG reagent was performed as a liver function test 1 to 2 weeks before surgery. ICG fluorescent imaging was performed using the PDE infrared camera. RESULTS: ICG fluorescent imaging was useful for liver surgical navigation as follows: three cases of recurrent hepatocellular carcinoma(HCC) after transcatheter arterial chemoembolization or thermal ablation therapy; three cases of colorectal metastatic liver tumors after chemotherapy as conversion therapy; two cases of intrahepatic cholangiocellular carcinoma (ICC); and two cases of surface HCC that were not detected by preoperative computed tomography (CT) scan. In the ICC cases, although dilatation of the bile duct could be detected, the tumor margins were ambiguous by ultrasonography(US). ICG fluorescent imaging clearly described the dilatation of the bile duct including the tumor. CONCLUSIONS: ICG fluorescent imaging was useful for liver surgical navigation including selection of the mode of hepatic resection.


Assuntos
Diagnóstico por Imagem/métodos , Verde de Indocianina , Neoplasias Hepáticas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade
14.
Gan To Kagaku Ryoho ; 39(12): 2231-3, 2012 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-23268033

RESUMO

In 2006, a 70-year-old man who underwent low anterior resection for rectal cancer (SS, N0, H1, Stage IV)at a nearby hospital was referred to our hospital. He was noted to have multiple liver metastases of approximately 1 cm in diameter in S2, S3, S6, and S7, and was subsequently treated with chemotherapy for 5 courses of mFOLFOX6 regimen. He achieved a complete response radiographically. Thereafter, he underwent lateral segmentectomy of the liver and was noted to have residual tumor cells by histopathological examination of the resected tissue. Seven months after the hepatectomy, recurrence occurred in S6 and S7 and a new lesion in S8 was noted. He then underwent 12 courses of mFOLFOX6. As of June 2012, the patient is alive without recurrence. A prolonged survival may be possible if downstaging is achieved with successful chemotherapy. However, similar to the present case, the detection of residual cancer cells during histopathological examination of the resected tissues has been reported in the literature. Thus, further investigation is needed to determine the optimal treatment of cases achieving a radiographic complete response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Fluoruracila/administração & dosagem , Hepatectomia , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Radiografia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia
15.
Clin J Gastroenterol ; 15(3): 623-629, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35304706

RESUMO

Undifferentiated carcinoma (UC) is relatively rare among gallbladder cancers, and the prognosis is poor compared to gallbladder adenocarcinoma. We report a 64-year-old man with gallbladder UC who underwent radical surgery and achieved long-term survival. He presented with a chief complaint of abdominal distension and loss of appetite. An abdominal computed tomography (CT) scan revealed a gallbladder tumor with a major axis of 120 mm that appeared to directly infiltrate the hepatic bed. No major vascular infiltration was noted, but the left and right intrahepatic bile ducts were dilated. On admission, the serum CRP level was 16.5 mg/dL; cholangitis and cholecystitis were suspected. He was hospitalized, treated with antibiotics, and underwent bile duct drainage; however, inflammation recurred and chemotherapy was not possible. Thus, three right liver areas, the caudate lobe, and the gallbladder were extirpated. Histopathologic examination showed a 130 × 90 mm tumor with extensive infiltration, hemorrhage, and necrosis in the liver. In the area occupied by the tumor, multinucleated cell proliferation, and polygonal and spindle-shaped tumor cells were noted. Based on the above findings, a diagnosis of UC was established. Postoperatively, gemcitabine and cisplatin were continued as adjuvant chemotherapy. No tumor recurrence has been detected after 24 months of follow-up care.


Assuntos
Carcinoma , Neoplasias da Vesícula Biliar , Carcinoma/diagnóstico por imagem , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia , Humanos , Inflamação/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia
16.
Mol Ther Oncolytics ; 25: 225-235, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35615265

RESUMO

Malignant soft tissue tumors, particularly highly malignant leiomyosarcomas, are resistant to chemotherapy and associated with a poor prognosis. T-01, a third-generation genetically modified herpes simplex virus type 1, replicates in tumor cells alone and exerts a cell-killing effect. The current study aimed to investigate the antitumor effect of T-01, which is a novel treatment for leiomyosarcoma. In vitro, six human cell lines and one mouse sarcoma cell line were assessed for T-01 cytotoxicity. In vivo, the efficacy of T-01 was examined in subcutaneously transplanted leiomyosarcoma (SK-LMS-1) cells and subcutaneously or intraperitoneally transplanted mouse sarcoma (CCRF S-180II) cells. Cytokines were assessed using ELISpot assay with splenocytes from the allogeneic models for immunological evaluation. T-01 showed cytotoxicity in all seven cell lines (p < 0.001). In the SK-LMS-1 xenotransplantation model, tumor growth was suppressed by T-01 administration (p = 0.02). In the CCRF S-180II subcutaneous tumor model, bilateral tumor growth was significantly suppressed in the T-01-treated group compared with the control group (p < 0.001). In the peritoneal dissemination model, T-01 treatment caused significant survival prolongation compared with the control (p < 0.01). In conclusion, third-generation genetically modified herpes simplex virus type 1 may be an effective novel therapy against refractory sarcomas.

17.
Hepatol Int ; 16(1): 135-147, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34973129

RESUMO

BACKGROUND/PURPOSE OF THE STUDY: Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients. METHODS: Somatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array. RESULTS: The samples were classified into the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 months vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence. CONCLUSION: CC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Variações do Número de Cópias de DNA , Humanos , Neoplasias Hepáticas/genética
18.
Cancers (Basel) ; 14(6)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35326554

RESUMO

Background/Aim: Nutritional assessment is known to be important for predicting prognosis in patients with malignant diseases. This study examined the usefulness of a prognostic predictive nutritional assessment tool for hepatocellular carcinoma (HCC) patients treated with surgical resection. Materials/Methods: HCC patients (n = 429) classified as Child−Pugh A who underwent an R0 resection between 2010 and 2020 were retrospectively analyzed (median age 73 years, males 326 (76.0%), Child−Pugh score 5:6 = 326:103, single tumor 340 (79.2%), median tumor size 3.5 cm, open:laparoscopic = 304:125). Glasgow prognostic score (GPS) and the newly developed neo-GPS method, which uses albumin−bilirubin grade 1 instead of albumin, were evaluated to compare their usefulness for prognosis prediction. Results: Median survival time for patients with a GPS score of 0, 1, and 2 was 120, 51, and 20 months, respectively. As for neo-GPS, that for those with a score of 0, 1, and 2 was not applicable (NA), 53 months, and 35 months, respectively (each p < 0.001; c-index: 0.556 and 0.611, respectively). Furthermore, median progression-free survival was 33, 22, and 9 months, and 41, 24, and 15 months, respectively (each p < 0.001; c-index: 0.539 and 0.578, respectively). As compared to patients with a high GPS (≥1), those with a high neo-GPS (≥1) showed a greater rate of high Clavien−Dindo classification (≥3) (39.2% vs. 65.1%). A comparison of patients with a high GPS (≥1) with those with a high neo-GPS (≥1) showed no significant difference regarding frequency of open or laparoscopic hepatectomy (17.4% vs. 15.2%, p = 0.670; 44.7% vs. 43.2%, p = 0.831, respectively), while the frequency of high Clavien−Dindo classification (≥3) was lower in patients who underwent a laparoscopic hepatectomy (11.2% vs. 22.7%, p = 0.007). Conclusion: The present findings suggest that the newly developed neo-GPS based on ALBI grade is an effective prognostic nutritional assessment tool and can be used for prediction of postoperative complications.

19.
Cancers (Basel) ; 14(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36358711

RESUMO

We developed and evaluated a modified albumin-bilirubin grade and α-fetoprotein (mALF) score, a nutritional and oncological assessment tool for patients with hepatocellular carcinoma (HCC) after surgical resection. Patients (n = 480) who underwent R0 resection between 2010 and 2020 were analyzed retrospectively. The mALF score assigned one point for a modified albumin-bilirubin (mALBI) grade 2b or 3 and one point for an α-fetoprotein (AFP) level ≥ 100 ng/mL. Patients were classified by mALF scores of 0 (mALBI grade 1/2a, AFP < 100 ng/mL), 1 (mALBI grade 2b/3 or AFP ≥ 100 ng/mL), or 2 (mALBI grade 2b/3, AFP ≥ 100 ng/mL) points. Liver reserve deteriorated and cancer progressed with increasing score. Postoperative complications (Clavien−Dindo classification ≥ 3) differed significantly among groups. The 5-year recurrence-free survival (RFS) rates were 34.8%, 11.2%, and 0.0% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The 5-year overall survival (OS) rates were 66.0%, 29.7%, and 17.8% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The mALF score was an independent prognostic predictor of RFS and OS. In HCC, the mALF score was effective for predicting postoperative complications and long-term survival.

20.
Gan To Kagaku Ryoho ; 38(12): 2493-5, 2011 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-22202424

RESUMO

We report here the experience of the treatment with sorafenib for advanced hepatocellular carcinoma (HCC) in our department. Forty patients received the therapy of sorafenib until April 2011. Twenty seven unresectable advanced HCC, 7 lung metastasis, 6 bone metastasis, 3 abdominal lymph node metastasis, and 2 peritoneal dissemination were included. The median duration of sorafenib treatment was 197 days. Grade 3 adverse event occurred in 9 patients (22.5%), and grade 4 adverse event occurred in 1 patient (3%). The response rate and disease control rate were 5% and 55%, respectively (CR 2, PR 0, SD 20, PD 9). The median overall survival was 15.2 months, and median recurrence-free survival was 3.7 months. These results suggested that a prevention of adverse events would lead to a continued treatment with sorafenib, and could expect to have a prolonged survival in patients with advanced HCC.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Piridinas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Metástase Neoplásica , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/efeitos adversos , Sorafenibe , Tomografia Computadorizada por Raios X
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