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1.
Liver Cancer ; 10(5): 461-472, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34721508

RESUMO

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07-1.59), 1.07 (95% CI 0.89-1.28), 1.31 (95% CI 1.06-1.62), and 1.81 (95% CI 1.03-3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69-2.14), 1.33 (95% CI 1.02-1.73), and 1.58 (95% CI 1.04-2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46-1.57), 1.34 (95% CI 1.01-1.8), and 1.57 (95% CI 1.03-2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83-4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98-5.54) in those with tumors measuring ≥5 cm. Conclusions: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

2.
World J Surg ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34668046

RESUMO

BACKGROUND: The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. METHODS: Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. RESULTS: The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. CONCLUSIONS: Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

3.
Trials ; 22(1): 633, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530885

RESUMO

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach. METHODS/DESIGN: Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival. DISCUSSION: If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000041381 . Registered on 10 August 2020. ClinicalTrials.gov NCT04600063 . Registered on 22 October 2020.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirurgia , Humanos , Excisão de Linfonodo , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Hepatol Res ; 51(11): 1102-1114, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34476874

RESUMO

AIM: We investigated effects of direct-acting antiviral (DAA)-induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) for postoperative recurrence and survival. METHODS: Surgical outcomes in 18 patients with postoperative DAA-induced SVR (HCC-DAA group) were compared with those in 23 patients with preoperative DAA-induced SVR (DAA-HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence <1 year after surgery were excluded. RESULTS: Serum concentrations of aminotransferases improved 1 year after surgery in both the HCC-DAA and DAA-HCC groups. The number of HCC-DAA patients with albumin-bilirubin (ALBI) grade 1 increased from 11 to 15. The disease-free survival rate did not differ between HCC-DAA group (3 years, 60%) and the other two groups (DAA-HCC group, 92% and control group, 60%). The 3-year overall survival rates were better in the DAA-HCC group (84%) and HCC-DAA group (100%) than in the control group (46%; all ps < 0.05 according to Holm's test). Multivariable analysis revealed that tumor stage was an independent risk factor for postoperative recurrence, and ALBI grade at 1 year after surgery was predictive of postoperative survival, but DAA-induced SVR was neither. CONCLUSIONS: Although postoperative DAA-induced SVR itself may not suppress postoperative recurrence, improvement in liver function as a result of DAA administration after surgery may prolong postoperative survival.

5.
Ann Med Surg (Lond) ; 68: 102644, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34386231

RESUMO

Background: This study aimed to evaluate the prognostic impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma (HCC) in patients with alcohol-related liver disease (ALD). Patients and methods: In total, 92 patients with ALD-HCC who underwent initial and curative hepatic resection were identified, including 56 and 36 patients with and without alcohol abstinence, respectively. Results: The 3-, 5-, and 7-year recurrence-free survival (RFS) were 46%, 43%, and 37% in the abstinence group, and 61%, 36%, and 36% in the non-abstinence group, respectively (p = 0.71). The 3-, 5-, and 7-year overall survival (OS) were 91%, 76%, and 66% in the abstinence group, and 87%, 57%, and 44% in the non-abstinence group, respectively (p = 0.023). Multivariate analysis revealed that non-abstinence was an independent prognostic factor for OS (P = 0.026). The incidence rate of liver-related death including HCC-specific death, liver failure, and renal failure in cirrhosis (hepatorenal syndrome) between the non-abstinence and abstinence groups were 41.7% vs. 19.6% (p = 0.032). Worsening of the Child-Pugh grade at intrahepatic recurrence was more frequently observed in the non-abstinence (33.3%) than that in the abstinence group (6.5%) (p = 0.039). Conclusions: Alcohol abstinence might improve the long-term survival of patients with ALD-HCC undergoing hepatic resection.

6.
World J Surg ; 45(11): 3386-3394, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34244815

RESUMO

BACKGROUND: Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status. METHODS: This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively). RESULTS: Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29). CONCLUSIONS: Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos
7.
Clin J Gastroenterol ; 14(3): 858-865, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33811313

RESUMO

Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19-9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico
8.
Surgery ; 169(4): 922-928, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33190917

RESUMO

BACKGROUND: Extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection. METHODS: The participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping. RESULTS: Extrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3-5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively. CONCLUSION: We have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon's selection of treatment strategies for hepatocellular carcinoma patients.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Adulto , Idoso , Biomarcadores , Carcinoma Hepatocelular/cirurgia , Diagnóstico por Imagem , Feminino , Seguimentos , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Nomogramas , Curva ROC , Resultado do Tratamento , Carga Tumoral
9.
BMC Cancer ; 20(1): 1215, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302911

RESUMO

BACKGROUND: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. METHODS: Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. RESULTS: Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. CONCLUSIONS: Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.


Assuntos
Deferasirox/farmacologia , Desferroxamina/farmacologia , Furanos/farmacologia , Quelantes de Ferro/farmacologia , Ferro/deficiência , Cetonas/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Moduladores de Tubulina/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Caderinas/biossíntese , Caderinas/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Ferro/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Asian Pac J Cancer Prev ; 21(12): 3647-3654, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33369464

RESUMO

BACKGROUND: Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. METHODS: The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P. RESULTS: In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively. CONCLUSIONS: Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors.
.


Assuntos
Atrofia/mortalidade , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Hepatectomia/efeitos adversos , Litíase/cirurgia , Hepatopatias/cirurgia , Lesões Pré-Cancerosas/mortalidade , Idoso , Atrofia/etiologia , Atrofia/patologia , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/etiologia , Colangiocarcinoma/patologia , Feminino , Seguimentos , Humanos , Litíase/patologia , Hepatopatias/patologia , Masculino , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Prognóstico , Taxa de Sobrevida
11.
Oncol Lett ; 20(5): 180, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32934747

RESUMO

Currently, when determining treatment regimens, there is an emphasis on the quality of life (QOL), in addition to treatment efficacy. Especially in hormone receptor-positive breast cancer with distant metastases, unless death is imminent, a common first-line treatment is endocrine therapy, which has fewer side effects. In the present study, the differences in QOL were evaluated based on the age and prognostic indicators of 46 patients with hormone receptor-positive breast cancer with distant metastases (stage IV), who received first-line endocrine therapy at the Osaka City University Hospital (Osaka, Japan) between November 2007 and November 2016. QOL score before and after endocrine therapy was retrospectively analyzed, using the Quality of Life Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs-Breast (QOL-ACD-B). There was no significant association between age and any of the clinicopathological features investigated. However, the QOL score of the elderly patient group was significantly higher compared with that of the younger group in the 'Satisfaction with treatment and coping with disease' subcategory (P=0.008). The QOL score of the younger age group in the same subcategory was significantly improved by the treatment (P=0.013). The patients that had an increased overall QOL score 3 months after treatment initiation had a significant extension of progression-free survival (PFS) rate compared to the patients with decreased or no change in QOL (P=0.032). In conclusion, psychological stress was more prominent in younger patients with stage IV breast cancer treated with hormonal therapy compared with elderly patients. Importantly, improving QOL within the 3 months after treatment initiation could lead to longer PFS rate.

12.
J Surg Oncol ; 122(8): 1543-1552, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32856301

RESUMO

OBJECTIVE: To investigate the postoperative recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after liver resection in patients with and without the achievement of sustained virologic response (SVR) through the administration of direct-acting antivirals (DAA). METHODS: Among 28 patients with HCC detected after DAA-SVR (DAA group) and 197 patients with HCC who did not receive treatment for HCV infection or who did not achieve an SVR (control group) between January 2000 and July 2019, we performed propensity score matching (PSM) to avoid confounding differences between the two groups. RESULTS: After PSM, 28 patients in each group were selected for analysis. The DAA-SVR patients showed improved liver function at operation and at recurrence in comparison to the control group. The disease-free survival rate at 3 years after surgery was 69% in the DAA group and 35% in the control group, respectively (P = .021). In the DAA group, all three patients with recurrence met the Milan criteria and could be managed by curative treatments and none died of liver failure during the follow-up period. CONCLUSIONS: SVR status suppresses postoperative recurrence of HCV-related HCC detected after DAA-SVR. Improved liver function may contribute to the successful treatment and prevention of liver failure.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Hepacivirus/efeitos dos fármacos , Hepatectomia/mortalidade , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/virologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resposta Viral Sustentada
13.
Mol Clin Oncol ; 13(2): 195-202, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32714546

RESUMO

The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses may be evaluated by measuring tumor-infiltrating lymphocytes (TILs), which has been frequently verified clinically. In the present study, the prediction of the therapeutic effect of endocrine therapy by TILs on stage IV breast cancer was clinically analyzed. Data from 40 patients who underwent endocrine therapy as the initial drug therapy for stage IV breast cancer were used. The correlation between TILs, evaluated according to standard methods, and prognosis, including the efficacy of endocrine therapy, was investigated retrospectively. Patients with ≥50% lymphocytic infiltration were considered to have lymphocyte-predominant breast cancer (LPBC). An analysis of outcomes revealed no difference in progression-free survival (PFS; P=0.171), time to treatment failure (TTF; P=0.054), or overall survival (OS; P=0.641) between the high TIL (>10%) and low TIL (≤10%) groups. Patients with LPBC (≥50%) exhibited a significant prolongation of PFS (P=0.005, log-rank), TTF (P=0.001) and OS (P=0.027) compared with non-LPBC patients. On receiver operating characteristics (ROC) curve analysis, better results were obtained with LPBCs [area under the curve (AUC)=0.700] than with TILs (AUC=0.606). The present findings suggest that a high level of lymphocytic infiltration in the tumor stroma may serve as a predictor of the therapeutic efficacy of endocrine therapy in patients with stage IV estrogen receptor-positive breast cancer.

14.
World J Surg ; 44(11): 3901-3914, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32651603

RESUMO

BACKGROUND: This study aimed to evaluate the impact of the age-adjusted Charlson comorbidity index (ACCI) on outcomes after hepatic resection for hepatocellular carcinoma (HCC). METHODS: We assessed 763 patients who underwent hepatic resection for HCC. The ACCI scores were categorized as follows: ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7. RESULTS: A multivariate analysis showed that the odds ratios for postoperative complications in ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 0.71 (p = 0.41) and 4.15 (p < 0.001), respectively. The hazard ratios for overall survival of ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 1.52 (p = 0.023) and 2.45 (p < 0.001), respectively. The distribution of deaths due to HCC-related, liver-related, and other causes was 68.2%, 11.8%, and 20% in ACCI ≤ 5 group, 47.2%, 13.9%, and 38.9% in ACCI = 6 group, and 27.3%, 9.1%, and 63.6% in ACCI ≥ 7 group (p = 0.053; ACCI ≤ 5 vs. = 6, p = 0.19; ACCI = 6 vs. ≥ 7, p < 0.001; ACCI ≤ 5 vs. ≥ 7). In terms of the treatment for HCC recurrence in ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7 groups, adaptation rate of surgical resection was 20.1%, 7.3%, and 11.1% and the rate of palliative therapy was 4.3%, 12.2%, and 22.2%, respectively. CONCLUSIONS: The ACCI predicted the short-term and long-term outcomes after hepatic resection of HCC. These findings will help physicians establish a treatment strategy for HCC patients with comorbidities.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fatores Etários , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Comorbidade , Hepatectomia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Estudos Retrospectivos
15.
J Hepatobiliary Pancreat Sci ; 27(9): 622-631, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32621787

RESUMO

BACKGROUND/PURPOSE: Grade C postoperative pancreatic fistula (POPF), as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life-threatening complication after pancreatoduodenectomy (PD). This study aims to evaluate risk factors for Grade C POPF after PD. METHODS: This is a prospective, multicenter study based in Japan and Taiwan. Between December 2014 and May 2017, 3022 patients were enrolled in this study and 2762 patients were analyzed. We analyzed risk factors of Grade C POPF based on the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death). RESULTS: Among 2762 patients, 46 patients (1.7%) developed Grade C POPF after PD. The mortality rate of the 46 patients with Grade C POPF was 37.0%. On the multivariate analysis, six independent risk factors for Grade C POPF were found; BMI ≥ 25.0 kg/m2 , chronic steroid use, preoperative serum albumin <3.0 mg/dL, soft pancreas, operative time ≥480 minutes, and intraoperative transfusion. The c-statistic of our risk scoring model for Grade C POPF using these risk factors was 0.77. The score was significantly higher in Grade C POPF than in Grade B POPF (P < .001) or none/biochemical leak (P < .001). CONCLUSIONS: This prospective study showed risk factors for Grade C POPF after PD.


Assuntos
Fístula Pancreática , Pancreaticoduodenectomia , Humanos , Japão/epidemiologia , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Fatores de Risco , Taiwan
16.
Pancreatology ; 20(5): 984-991, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32680728

RESUMO

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.


Assuntos
Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Stents , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/cirurgia , Fístula Pancreática/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , República da Coreia , Stents/efeitos adversos , Resultado do Tratamento
17.
J Hepatobiliary Pancreat Sci ; 27(10): 682-689, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32578373

RESUMO

BACKGROUND: This study aimed to evaluate the prognostic impact of the 5-5-500 rule in patients after hepatic resection for the intermediate stage of hepatocellular carcinoma (HCC; The Barcelona Clinic Liver Cancer classification [BCLC] B). METHODS: 177 patients had hepatic resection for BCLC-B HCC. The 5-5-500 rule was defined by tumor size ≤5 cm in diameter, tumor number ≤5, and α-fetoprotein ≤500 ng/mL. RESULTS: The 3-, 5-, and 7-year recurrence-free survival rates were 22%, 14%, and 11% in patients within the 5-5-500 rule, and 16%, 10%, and 10% in patients beyond the 5-5-500 rule, respectively (P = .015). The 3-, 5-, and 7-year overall survival rates were 72%, 47%, and 34% in patients within the 5-5-500 rule, and 52%, 31%, and 25% in patients beyond the 5-5-500 rule, respectively (P = .035). Being beyond the 5-5-500 rule and liver cirrhosis were independent prognostic factors for recurrence-free survival. For overall survival, being beyond the 5-5-500 rule, age ≥65 years, Child-Pugh class B, and anti-hepatitis C antibody positive were identified as independent prognostic factors. CONCLUSIONS: The 5-5-500 rule could predict prognosis in BCLC-B patients with hepatic resection. Hepatic resection might provide survival benefit for selected patients with BCLC-B HCC within the 5-5-500 rule.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Recém-Nascido , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
18.
Anticancer Res ; 40(5): 2637-2644, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366408

RESUMO

BACKGROUND/AIM: There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. RESULTS: Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). CONCLUSION: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.


Assuntos
Carcinoma Ductal Pancreático/patologia , Criopreservação , Transplante de Fígado , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade
19.
Anticancer Res ; 40(5): 2881-2887, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366438

RESUMO

BACKGROUND/AIM: This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs). PATIENTS AND METHODS: A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8+ TILs were identified by immunohistochemical staining. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8+ TILs were longer than those with low CD8+ TILs. Preoperative NLR and CD8+ TILs were negatively correlated. CONCLUSION: NLR and CD8+ TILs were associated with OS and RFS in BTCs. NLR can predict CD8+ TILs infiltrating the cancer microenvironment.


Assuntos
Neoplasias do Sistema Biliar/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos/imunologia , Neutrófilos/imunologia , Idoso , Feminino , Humanos , Masculino
20.
Jpn J Radiol ; 38(6): 547-552, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32239373

RESUMO

PURPOSE: Hepatic infarction is a relatively rare life-threatening complication after pancreatoduodenectomy (PD). Computed tomography (CT) findings and risk factors for hepatic infarctions after PD were investigated. METHODS: One hundred-fifty three patients who underwent contrast-enhanced CT (CECT) after PD between January 2011 and August 2016 were retrospectively analyzed. Hepatic infarction was defined as the non-contrast enhanced area expanding to the liver surface without mass effect on CECT. The relationships between infarctions and preoperative laboratory data or surgical procedures using uni- and multivariate analyses were examined. RESULTS: Twenty-nine patients showed 47 hepatic infarctions on CT. Infarctions most commonly appeared in segment 7 (S7) (17 lesions, 36.2%). Lesions were wedge-shaped in 12 patients and spread over multiple hepatic segments in 11 patients. Univariate analysis identified celiac artery (CA) or common hepatic artery (CHA) resection (p = 0.0029) and portal vein (PV) resection (p = 0.013) as risk factors for infarctions. CA or CHA resection (p = 0.038) remained as a significant factor after multivariate logistic analysis. CONCLUSIONS: Hepatic infarctions after PD were most frequently seen in S7 and PV penetrating sign was characteristic CT findings. CA or CHA resection or PV resection were revealed as risk factors for hepatic infarctions.


Assuntos
Meios de Contraste , Infarto Hepático/diagnóstico por imagem , Pancreaticoduodenectomia , Complicações Pós-Operatórias/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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