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1.
Surg Today ; 54(7): 795-800, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38307970

RESUMO

PURPOSE: To evaluate the short term-outcomes of venous reconstruction using a round ligament-covered prosthetic vascular graft and assess its effectiveness in the prevention of prosthetic vascular graft migration in right­lobe living donor liver transplantation (LDLT). METHODS AND RESULTS: Thirty patients underwent reconstruction of the middle hepatic vein (MHV) tributaries during right lobe LDLT between January, 2021 and October, 2022. These patients were divided into the autologous vascular graft group (A group, n = 24) and the round ligament-covered prosthetic vascular graft group (RP group, n = 6). The computed tomography (CT) density ratio of the drainage area in the posterior segment of patent grafts was significantly higher in the RP group than in the A group (0.91 vs. 1.06, p = 0.0025). However, the patency rates of reconstructed MHV tributaries in the A and RP groups were 61% and 67%, respectively, with no significant difference between the groups (p = 0.72). Prosthetic vascular graft migration did not occur in the RP group. CONCLUSION: Venous reconstruction using round ligament-covered prosthetic vascular grafts is a feasible and simple method to prevent prosthetic vascular graft migration in right-lobe LDLT.


Assuntos
Prótese Vascular , Veias Hepáticas , Transplante de Fígado , Doadores Vivos , Humanos , Transplante de Fígado/métodos , Veias Hepáticas/cirurgia , Veias Hepáticas/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto , Ligamentos/cirurgia , Ligamentos/transplante , Procedimentos de Cirurgia Plástica/métodos , Resultado do Tratamento , Implante de Prótese Vascular/métodos , Grau de Desobstrução Vascular , Procedimentos Cirúrgicos Vasculares/métodos , Migração de Corpo Estranho/prevenção & controle , Migração de Corpo Estranho/cirurgia
2.
Surg Today ; 54(7): 812-816, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38170224

RESUMO

Living-donor liver transplantation (LDLT) is an established treatment for patients with end-stage liver disease or acute liver failure, and outflow reconstruction is considered one of the most vital techniques in LDLT. To date, many strategies have been reported to prevent outflow obstruction, which can be refractory to liver dysfunction and can cause life-threatening graft loss or mortality. In addition, in this era of laparoscopic hepatectomy in donor surgery, especially LDLT using a left liver graft, it has been predicted that cutting the hepatic vein with automatic linear staplers will lead to more outflow-related problems than with conventional open hepatectomy because of the short neck of the anastomosis orifice. We herein review 10 cases of venoplasty performed with a novel venous cuff system using a donor's round ligament around the hepatic vein in LDLT with a left lobe graft, which makes anastomosis of the hepatic vein sterically easy for postoperative venous patency.


Assuntos
Estudos de Viabilidade , Veias Hepáticas , Transplante de Fígado , Doadores Vivos , Veias Mesentéricas , Transplante de Fígado/métodos , Humanos , Veias Hepáticas/cirurgia , Veias Mesentéricas/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Anastomose Cirúrgica/métodos , Hepatectomia/métodos , Fígado/irrigação sanguínea , Fígado/cirurgia , Ligamentos Redondos/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Laparoscopia/métodos
3.
J Gastroenterol Hepatol ; 39(3): 576-586, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38084637

RESUMO

AIM: Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). METHODS: We enrolled 114 patients with u-HCC treated with ATZ/BEV (n = 48) or lenvatinib (n = 66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). RESULTS: Twenty-three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV-eosinophil-high group, which had better responses than the ATZ/BEV-eosinophil-low group (P = 0.0090). Kaplan-Meier curves revealed a trend toward significantly better progression-free survival (PFS) in the ATZ/BEV-eosinophil-high group than the ATZ/BEV-eosinophil-low group (the median PFS: 4.7 months in the ATZ/BEV-eosinophil-low group vs 12.6 months in the ATZ/BEV-eosinophil-high group; P = 0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P = 0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02-4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV-eosinophil-high group (P = 0.0285). The outcomes did not significantly differ between the LEN-eosinophil-high group and the LEN-eosinophil-low group. CONCLUSION: A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u-HCC and was associated with the incidence of AEs (≥ grade 3).


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Eosinófilos , Neoplasias Hepáticas/tratamento farmacológico
4.
Surg Today ; 54(1): 64-72, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37289265

RESUMO

PURPOSE: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. METHODS: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. RESULTS: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. CONCLUSION: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Japão , Resultado do Tratamento , Doadores Vivos , Recidiva Local de Neoplasia
5.
Clin J Gastroenterol ; 17(1): 93-99, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37751079

RESUMO

Chronic expanding hematoma (CEH) is defined as a hematoma that grows slowly over a month or longer. CEH with a primary hepatic origin is extremely rare. An 85-year-old man presented with general malaise and low-grade fever. His medical history included hypertension and postoperative appendicitis, and he was taking oral aspirin. Computed tomography showed a 7-cm mass in liver S7 with calcification at the margin. On contrast-enhanced magnetic resonance imaging, the inside of the mass showed heterogeneous hyperintensity on T1-weighted images, mainly low intensity on T2-weighted images, and mild hyperintensity in some areas. Under the preoperative diagnosis of suspected CEH, hemorrhagic cyst, or hepatocellular carcinoma, S7 partial liver resection and cholecystectomy were performed. Histopathological findings showed that the mass was continuous with the liver and protruded extrahepatically, and was covered with a hard fibrous capsule. The capsule contained hematomas ranging from obsolete to relatively fresh, with no neoplastic lesions. He was diagnosed with CEH in the liver. This subcapsular hepatic hematoma was pathologically shown to be a CEH. Complete surgical resection was effective in treating this CEH in the liver.


Assuntos
Hematoma , Tomografia Computadorizada por Raios X , Masculino , Humanos , Idoso de 80 Anos ou mais , Doença Crônica , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematoma/cirurgia , Imageamento por Ressonância Magnética , Fígado/diagnóstico por imagem , Fígado/patologia
6.
Surg Case Rep ; 9(1): 173, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773552

RESUMO

BACKGROUND: Liver metastasis of pure squamous cell carcinoma (SCC) from pancreatic ductal adenocarcinoma has not been previously reported. CASE PRESENTATION: A 66-year-old man underwent a computed tomography scan 3 years after surgery for pancreatic head cancer, and the scan revealed a mass lesion in the right lobe of the liver. A liver tumor biopsy was performed, and SCC was diagnosed. Whole sections of the pancreatic head cancer were re-evaluated, but no areas of SCC-like differentiation were identified. Although the pathology differed between the pancreas and liver, metastasis of adenosquamous carcinoma was considered. Three courses of gemcitabine plus nab-paclitaxel were administered to treat the liver metastasis of pancreatic cancer, but no response was attained. Therefore, primary SCC of the liver was considered and hepatic resection was performed. The tumor had invaded the diaphragm, and S5/6 partial hepatic resection with right diaphragm resection was performed. Pathological examination showed pure SCC of the liver, which differed from the pancreatic cancer. KRAS mutations were evaluated in the pancreatic and liver tumor specimens, and Q61R mutation was identified in both specimens. This pure SCC of the liver was diagnosed as metastasis from pancreatic cancer not by histology but by genetic analysis. CONCLUSIONS: This is the first reported case of pure SCC liver metastasis from pancreatic cancer without a squamous cell component in the primary tumor. Evaluation of KRAS mutations in both specimens was useful for diagnosis.

7.
J Surg Case Rep ; 2023(8): rjad485, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37645700

RESUMO

Surgical therapy following lenvatinib (LEN) plus transarterial chemoembolization (TACE) is a useful therapeutic option for intermediate-stage hepatocellular carcinoma (HCC). A 66-year-old man with a history of hepatitis C was detected four masses in the caudate lobe and segment 6/7 of the liver, with a maximum lesion diameter of 14 cm by computed tomography. The patient was diagnosed with intermediate-stage HCC and received LEN plus TACE. After resuming LEN for 8 weeks, computed tomography showed weakened stained areas of the tumors, and no new lesions. Thus, the patient was evaluated as having a partial response in the modified Response Evaluation Criteria in Solid Tumors. The patient underwent hepatic caudate lobectomy, partial hepatectomy of S6/7, and S6 microwave coagulation therapy for radical resection. The patient is currently alive and recurrence-free at 12 months postoperatively. In patients with multiple HCC lesions, hepatic resection combined with local therapy might be an effective treatment option.

8.
J Hepatobiliary Pancreat Sci ; 30(9): 1089-1097, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37548316

RESUMO

PURPOSE: To evaluate the prognostic impact of dynamic gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data of 206 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI and hepatectomy and quantitatively evaluated the signal intensity ratio of the tumor to the surrounding liver tissue in the portal phase (SIRPP). We verified the survival rates and assessed the prognostic factors associated with overall survival (OS) and recurrence-free survival (RFS) using SIRPP. RESULTS: Multivariate analysis revealed that the independent predictive factors for poorly-differentiated HCC were α-fetoprotein > 20 ng/mL (hazard ratio [HR]: 3.1909, 95% confidence interval [CI]: 1.3464-7.5622, p = .0084) and SIRPP ≤ 0.85 (HR: 3.7155, 95% CI: 1.521-9.076, p = .004). The 5-year OS and RFS rates in the high and low SIRPP groups were 83.2 and 52.1%, respectively (p < .0001) and 49.7 and 18.5%, respectively (p = .0003). Multivariate analysis revealed that SIRPP ≤ 0.68 was an independent prognostic factor related to OS (HR: 4.4537, 95% CI: 1.6581-11.9626, p = .003). CONCLUSION: The SIRPP of preoperative Gd-EOB-DTPA-enhanced MRI might predict the histological differentiation and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Meios de Contraste , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos
9.
PLoS One ; 18(7): e0288033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450554

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, and such early recurrence (ER) is associated with a poor prognosis. Predicting ER is useful for determining the optimal treatment. METHODS: One hundred fifty-three patients who underwent pancreatectomy for PDAC were divided into an ER group (n = 54) and non-ER group (n = 99). Clinicopathological factors were compared between the groups, and the predictors of ER and prognosis after PDAC resection were examined. RESULTS: The ER group had a higher platelet count, higher platelet-to-lymphocyte ratio (PLR), higher preoperative CA19-9 concentration, higher SPan-1 concentration, larger tumor diameter, and more lymph node metastasis. The receiver operating characteristic (ROC) curve analysis identified cut-off values for PLR, carbohydrate antigen 19-9 (CA19-9), SPan-1, and tumor diameter. In the multivariate analysis, a high PLR, high CA19-9, and tumor diameter of >3.1 cm were independent predictors of ER after resection (all p < 0.05). When the parameter exceeded the cut-off level, 1 point was given, and the total score of the three factors was defined as the ER prediction score. Next, our new ER prediction model using PLR, CA19-9 and tumor diameter (Logit(p) = 1.6 + 1.2 × high PLR + 0.7 × high CA19-9 + 0.5 × tumor diameter > 3.1cm) distinguished ER with an area under the curve of 0.763, a sensitivity of 85.2%, and a specificity of 55.6%. CONCLUSIONS: ER after resection of PDAC can be predicted by calculation of a score using the preoperative serum CA19-9 concentration, PLR, and tumor diameter.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antígeno CA-19-9 , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/cirurgia , Prognóstico , Neoplasias Pancreáticas
10.
Int J Clin Oncol ; 28(8): 1082-1091, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247134

RESUMO

BACKGROUND: The hemoglobin-albumin-lymphocyte-platelet (HALP) score is a combination index that assesses nutritional status and systemic inflammatory response and is reported to predict prognosis in several cancer types. However, researches about the usefulness of the HALP score in intrahepatic cholangiocarcinoma (ICC) are limited. METHODS: This was a single-center, retrospective study of 95 patients who underwent surgical resection for ICC between 1998 and 2018. We divided patients into two groups by calculating the cutoff value of the HALP score and examined clinicopathological characteristics, prognosis, and sarcopenia. Tumor-infiltrating lymphocytes (TILs), CD8 + TILs, and FOXP3 + TILs were evaluated by immunohistochemical staining of resected tumors. RESULTS: Of 95 patients, 22 were HALP-low. The HALP-low group had significantly lower hemoglobin (p = 0.0007), lower albumin (p = 0.0013), higher platelet counts (p < 0.0001), fewer lymphocytes (p < 0.0001), higher CA19-9 levels (p = 0.0431), and more lymph node metastasis (p = 0.0013). Multivariate analysis revealed that the independent prognostic factors for disease-free survival were maximum tumor size (≥ 5.0 cm) (p = 0.0033), microvascular invasion (p = 0.0108), and HALP score (≤ 25.2) (p = 0.0349), and that factors for overall survival were lymph node metastasis (p = 0.0020) and HALP score (≤ 25.2) (p = 0.0014). The HALP-low group contained significantly more patients with sarcopenia (p = 0.0015). Immunohistochemistry showed that counts of CD8 + TILs were significantly lower in the HALP-low group (p = 0.0075). CONCLUSIONS: We demonstrated that low HALP score is an independent prognostic factor for ICC patients undergoing curative hepatic resection and is associated with sarcopenia and the immune microenvironment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Sarcopenia , Humanos , Prognóstico , Estudos Retrospectivos , Metástase Linfática/patologia , Sarcopenia/cirurgia , Sarcopenia/patologia , Albuminas , Linfócitos/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Hemoglobinas/análise , Microambiente Tumoral
11.
Clin J Gastroenterol ; 16(4): 559-566, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37046144

RESUMO

We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4 years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12 months, and she was alive 18 months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3 years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17 months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3 years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30 months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence.


Assuntos
Carcinoma Hepatocelular , Técnica de Fontan , Laparoscopia , Neoplasias Hepáticas , Masculino , Feminino , Humanos , Pré-Escolar , Adulto , Adulto Jovem , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatectomia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Recidiva Local de Neoplasia/cirurgia
12.
Hepatol Res ; 53(8): 723-736, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36998205

RESUMO

AIM: We aimed to evaluate the association between the intraoperative indocyanine green (ICG) fluorescence imaging (FI) pattern, preoperative magnetic resonance imaging (MRI) findings using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), preoperative diffusion-weighted imaging (DWI) of MRI, and histological differentiation of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data for 80 tumors of 64 patients. Intraoperative ICG FI patterns were classified into cancerous or rim-positive type. We evaluated the signal intensity ratio of the tumor and the surrounding liver tissue in the portal phase (SIRPP) and intensity in the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced MRI, the apparent diffusion coefficient (ADC) in the DWI of MRI, and clinicopathologic factors. RESULTS: In the rim-positive group, the rate of poorly differentiated HCC and hypointensity type in HBP were significantly higher, and SIRPP and ADC were significantly lower than the rim-negative group. In the cancerous group, the rate of well or moderately differentiated HCC and hyperintensity type in HBP, SIRPP, and ADC were significantly higher than the noncancerous group. Multivariate analysis identified low SIRPP, low ADC, and hypointensity type in HBP as the significant predictive factors for rim-positive HCC and high SIRPP, high ADC, and hyperintensity type in HBP as the significant predictive factors for cancerous HCC. The positive rate of programmed cell death 1-ligand 1 and vessels that encapsulate tumor clusters status of the rim-positive HCC and HCC with low SIRPP were significantly higher than the control group. CONCLUSIONS: The intraoperative ICG FI pattern of HCC closely correlated with histological differentiation, preoperative SIRPP and intensity type in the Gd-EOB-DTPA MRI, and preoperative ADC in the DWI of MRI.

14.
Ann Surg Oncol ; 30(6): 3378-3389, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36641515

RESUMO

BACKGROUND: Signal regulatory protein alpha (SIRPα), expressed in the macrophage membrane, inhibits phagocytosis of tumor cells via CD47/SIRPα interaction, which acts as an immune checkpoint factor in cancers. This study aimed to clarify the clinical significance of SIRPα expression in hepatocellular carcinoma (HCC). METHODS: This study analyzed SIRPα expression using RNA sequencing data of 372 HCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of our 189 HCC patient cohort. The correlation between SIRPα expression and clinicopathologic factors, patient survival, and intratumor infiltration of immune cells was investigated. RESULTS: Overall survival (OS) was significantly poorer with high SIRPα expression than with low expression in both TCGA and our cohort. High SIRPα expression correlated with lower recurrence-free survival (RFS) in our cohort. High SIRPα expression was associated with higher rates of microvascular invasion and lower serum albumin levels and correlated with greater intratumor infiltration of CD68-positive macrophages and myeloid-derived suppressor cells (MDSCs). Multivariate analysis showed that SIRPα expression and high infiltration of CD8-positive T cells and MDSCs were predictive factors for both RFS and OS. Patients with high SIRPα expression and infiltration of CD8-positive T cells and MDSCs had significantly lower RFS and OS rates. In spatial transcriptomics sequencing, SIRPα expression was significantly correlated with CD163 expression. CONCLUSIONS: High SIRPα expression in HCC indicates poor prognosis, possibly by inhibiting macrophage phagocytosis of tumor cells, promoting MDSC infiltration and inducing antitumor immunity. Treatment alternatives using SIRPα blockage should be considered in HCC as inhibiting macrophage antitumor immunity and MDSCs.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Relevância Clínica , Neoplasias Hepáticas/genética , Fagocitose , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo
15.
Int Cancer Conf J ; 12(1): 81-86, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36605838

RESUMO

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide, and the mortality rate of patients with unresectable HCC is very high. Microsatellite instability (MSI) is an essential biomarker for response to immune checkpoint inhibitors (ICI) in various tumors. However, the frequency of MSI in HCC is low (1.11%). There is only one case report of MSI-high HCC, and it is not well understood how high MSI affects the tumor microenvironment of HCC. Hence, we describe an interesting patient with unresectable MSI-high HCC, including the evaluation of immune status in the tumor microenvironment. A 68-year-old man presented to our department with HCC in liver segment 1. Contrast-enhanced CT revealed a liver tumor of 6.0 cm in maximum size. The patient underwent extended left and caudate lobectomy of the liver for HCC. Four months after surgical resection, contrast-enhanced computed tomography (CECT) detected 13 recurrent nodules. The patient was diagnosed with unresectable hepatocellular carcinoma recurrence, and we decided to administer systematic chemotherapy. Lenvatinib was administered over approximately 2 years as a first-line treatment, which resulted in intrahepatic tumor shrinkage. However, follow-up CECT showed new lesions, hepatogastric mesentery lymph node swelling, and peritoneal dissemination. After MSI-high status was identified, the patient began to receive pembrolizumab (200 mg, every 3 weeks). Eleven cycles of pembrolizumab therapy were administered over approximately 8 months, during which the diameter of the hepatogastric mesentery lymph node swelling and peritoneal dissemination showed shrinkage but later re-increased. As the third- and fourth-line therapy has been administered, the tumors and lymph nodes have shrunk. We report a rare case in which multikinase inhibitors were effectively used to treat MSI-high HCC.

16.
Hepatol Res ; 53(6): 522-530, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36719705

RESUMO

AIM: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score reflects the immune system and the nutritional status of patients, and prognosis in various cancers. However, the HALP score in hepatocellular carcinoma has not been reported. METHODS: Data were analyzed retrospectively from Child-Pugh A patients undergoing hepatic resection for single hepatocellular carcinoma ≤5 cm. For cross-validation, patients were divided into the training (332 patients) and validation cohort (210 patients). In the training cohort, we divided patients into two groups by appropriate cut-off value of the HALP score, and univariable and multivariable analyses were conducted for disease-free and overall survival (OS) between two groups. In the validation cohort, we examined OS by Kaplan-Meier analysis in the same cut-off value of the HALP score in the training cohort. RESULTS: The HALP-low group was significantly older (p = 0.0003), had fewer hepatitis B surface antigen-positive patients (p = 0.0369), higher prothrombin time (p = 0.0141), lower fibrosis-4 index (p = 0.0206), bigger maximum tumor size (p = 0.0196), and less histological liver fibrosis (p = 0.0077). Multivariate analysis showed that the independent prognostic factors for disease-free survival were fibrosis-4 index ≥2.67 (p = 0.0008), simple nodular type with extranodular growth or confluent multinodular type (p = 0.0221), and intrahepatic metastasis (p = 0.0233), and that for OS were fibrosis-4 index ≥2.67 (p = 0.0020), HALP ≤45.6 (p = 0.0228), and poor differentiation (p = 0.0305). In the validation cohort, Kaplan-Meier analysis revealed the trend toward significantly impaired OS (p = 0.0220) in the HALP-low group. CONCLUSION: We showed that a low HALP score is the independent prognostic factor for Child-Pugh A patients undergoing curative hepatic resection for single and small hepatocellular carcinoma.

17.
Cancer Sci ; 114(3): 937-947, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36369960

RESUMO

The association between tumor microenvironment (TME) and cancer-associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR-493-5p on tumor cell lines were examined. Additionally, databases were used to identify miR-493-5p targets, and the relationship between prognosis of ICC patients and cocaine- and amphetamine-regulated transcript propeptide (CARTPT), one of the targets of miR-493-5p, expression in ICC tissues was retrospectively analyzed. Compared with NF-derived CM and EVs, CAF-derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR-493-5p was significantly increased in CAF-derived EVs compared to NF-derived EVs. Tumor cell lines transfected with miR-493-5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence-free survival rates were significantly worse in the CARTPT-negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence-free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR-493-5p in EVs.


Assuntos
Neoplasias dos Ductos Biliares , Fibroblastos Associados a Câncer , Colangiocarcinoma , MicroRNAs , Humanos , Fibroblastos Associados a Câncer/metabolismo , Estudos Retrospectivos , MicroRNAs/genética , Proliferação de Células , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Microambiente Tumoral/genética
18.
Transplant Proc ; 55(1): 191-196, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36564321

RESUMO

Recurrence of hepatocellular carcinoma (HCC) after living donor liver transplant (LDLT) is an essential factor defining prognosis, and surgical resection is the only curative treatment. However, the factors that define whether surgical resection is possible remain unclear. Here, we compared resectable and unresectable HCC recurrence cases after LDLT and examined factors that determine whether surgical resection is possible. Resectable (n = 17) and unresectable (n = 14) groups among 264 patients who underwent LDLT for HCC from January 1999 to March 2020 were compared and examined for recurrence type, prognosis, and clinicopathologic factors. Overall survival after LDLT (median, 8.5 vs 1.7 years, P < .01) was significantly longer in the resectable group. In univariate analysis, female recipient rate, lymphocyte to monocyte ratio (LMR) ≥2.75, and tumor size ≤5.0 cm were significantly higher in the resectable group. Younger donors, lower Model for End-Stage Liver Disease scores, lower graft volume, and lower graft volume to standard liver volume ratio were evident in the resectable group. In multivariate analysis, female recipient rate (P = .0034) and LMR ≥2.75 (P = .0203) were independent predictive factors for resectable HCC recurrence after LDLT. Female recipient and LMR ≥2.75 before transplant could predict the surgically resectable type of HCC recurrence after LDLT.


Assuntos
Carcinoma Hepatocelular , Doença Hepática Terminal , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Feminino , Carcinoma Hepatocelular/patologia , Doadores Vivos , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento
19.
Hepatol Res ; 53(5): 432-439, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36583569

RESUMO

AIMS: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). METHODS AND RESULTS: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. CONCLUSION: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.

20.
Transplant Proc ; 54(10): 2791-2793, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36396466

RESUMO

Although there have been a few liver transplantations (LTs) between identical twins, to our knowledge hepatic damage after LT in an immunosuppressant-free patient has not been reported. Autoimmune liver disease recurrence after LT is also a postoperative problem. In this follow-up to our previous report, we present the case of a 57-year-old man with acute liver failure who underwent living donor liver transplantation (LDLT) from an identical twin. Six months after LDLT, the patient was free from immunosuppressive medication and showed good liver function. However, 1 year after LDLT, he developed liver damage and was diagnosed with autoimmune hepatitis by liver biopsy. His liver function was improved with steroid pulse therapy and the resumption of immunosuppressive medications. Even after LDLT from an identical twin, careful management is required for patients to remain free of immunosuppressive medications, considering the background liver disease.


Assuntos
Hepatite Autoimune , Transplante de Fígado , Masculino , Humanos , Pessoa de Meia-Idade , Doadores Vivos , Transplante de Fígado/efeitos adversos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/cirurgia , Gêmeos Monozigóticos , Hospedeiro Imunocomprometido , Resultado do Tratamento
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