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1.
World J Surg ; 47(7): 1772-1779, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37000199

RESUMO

BACKGROUND: Although previous studies have noted the potential benefit of early drain removal (EDR) after pancreatoduodenectomy (PD), there is a paucity of data on the timing of drain removal utilizing a national database that reflect the "real world" setting. Given the ongoing controversy related to PD drain use and management, we sought to define trends in drain use among a large national cohort, as well as identify factors associated with EDR following PD. METHODS: The ACS NSQIP targeted pancreatectomy database was used to identify patients who underwent PD between 2014 and 2020. The trend in proportion of patients with EDR (removal ≤ POD3) as well as predictors of EDR were assessed. Risk-adjusted postoperative outcomes were evaluated by multivariable regression analysis. RESULTS: Among 14,356 patients, 16.2% of patients (N = 2324) experienced EDR, and the proportion of patients with EDR increased by 68% over the study period (2014: 10.9% vs. 2020: 18.3%, p < 0.001). Higher drain fluid amylase on POD1-3 [LogWorth (LW) = 44.3], operative time (LW = 33.2), and use of minimally invasive surgery (LW = 14.0) were associated with EDR. Additionally, EDR was associated with decreased risk of overall and serious morbidity, PD-related morbidity (e.g., pancreatic fistula), reoperation, prolonged length of stay and readmission (all p < 0.05). CONCLUSIONS: Routine drain placement remains a common practice among most surgeons. EDR following PD increased over time was associated with lower post-operative complications and shorter LOS. Despite evidence that EDR was safe and may even be associated with lower complications, only 1 in 6 patients were managed with EDR.


Assuntos
Pancreatectomia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Pancreatectomia/efeitos adversos , Fístula Pancreática/etiologia , Fístula Pancreática/complicações , Drenagem/efeitos adversos , Cuidados Pós-Operatórios/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
2.
Ann Surg Oncol ; 29(4): 2393-2405, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34994885

RESUMO

BACKGROUND: Surgical resection is the only curative strategy for perihilar cholangiocarcinoma (PHC), but recurrence rates are high even after purported curative resection. This study aimed to evaluate the efficacy and safety of gemcitabine/S-1 (GS) combination chemotherapy in the neoadjuvant setting. METHODS: In an open-label, single-arm, phase 2 study, neoadjuvant chemotherapy (NAC) with GS, repeated every 21 days, was administered for three cycles to patients with histologic or cytologically confirmed borderline resectable (BR) PHC who were eligible for inclusion in the study. In this study, BR PHC was defined as positive for lymph node metastasis and for cancerous vascular invasion or Bismuth type 4 on preoperative imaging. The primary end point consisted of the 3- and 5-year survival rates. The secondary end points were feasibility, resection rate, and pathologic effect. RESULTS: The study enrolled 60 patients between January 2011 and December 2016. With respect to toxicity, the major adverse effect was neutropenia, which reached grade 3 or 4 in 53.3% of cases. The overall disease control rate was 91.3%. The median survival time for the entire cohort was 30.3 months. For all the patients, the estimated 3-year survival rate was 44.1%, and the 5-year survival rate was 30.0%. Resection with curative intent was performed for 43 (71%) of the 60 patients. For 81% of the resected patients, R0 resection was performed, and Clavien-Dindo grade 3 complications or a higher morbidity rate was seen in 41% of the patients. The median survival time was 50.1 months for the resected and 14.8 months for the unresected patients. For the resected patients, the estimated 3-year survival rate was 55.8%, and the estimated 5-year survival rate was 36.4%. CONCLUSIONS: Gemcitabine/S-1 combination NAC has promising efficacy and good tolerability for patients with BR PHC.


Assuntos
Neoplasias dos Ductos Biliares , Tumor de Klatskin , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/cirurgia , Desoxicitidina/análogos & derivados , Humanos , Tumor de Klatskin/tratamento farmacológico , Tumor de Klatskin/cirurgia , Terapia Neoadjuvante/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Gencitabina
3.
Transpl Int ; 35: 10276, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592448

RESUMO

A duct-to-duct-biliary-anastomosis is the preferred biliary reconstruction technique in liver transplantation; biliary complications remain the major concerns for the technique. We examined the significance of the intramural vascular network of the extrahepatic bile duct (EBD) and its relevant vessels. We microscopically examined the axial sections of the EBD with 5 mm intervals of 10 formalin-fixed deceased livers. The luminal-areas of the 3 and 9 o'clock arteries correlated significantly and positively with the distance from the bifurcation of the right and left hepatic ducts (the 3 o'clock artery, r = 0.42, p < 0.001; the 9 o'clock artery, r = 0.39, p < 0.001); the ratios of the numbers of the intramural vessels to the areas of the corresponding sections of the EBD significantly correlated positively with the distance from the bifurcation of the right and left hepatic ducts (total vessels, r = 0.78, p < 0.001; arterioles, r = 0.52, p < 0.001; venules, r = 0.45, p < 0.001). This study demonstrated that there is a significant locoregional distributional heterogeneity of the intramural vessels among the EBD. The hepatic arteries neighboring the EBD primarily supply the blood flow to the EBD; thus, when the broader isolation of the EBD from the neighboring arteries is necessary, this locoregional distributional heterogeneity of the intramural vessels may render the EBD likely to suffer ischemia of the anastomotic site.


Assuntos
Ductos Biliares Extra-Hepáticos , Procedimentos Cirúrgicos do Sistema Biliar , Transplante de Fígado , Anastomose Cirúrgica/métodos , Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Humanos , Transplante de Fígado/métodos , Doadores Vivos
4.
HPB (Oxford) ; 24(9): 1551-1559, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35428586

RESUMO

BACKGROUND: Estimation of mortality risk traditionally has only included preoperative factors. We sought to develop "real-time" mortality risk-calculator for patients who undergo pancreatoduodenectomy (PD) based on preoperative factors, as well as events that occurred during the course of patient's surgery and hospitalization. METHODS: Patients who underwent PD from 2014 to 2018 were identified in the ACS-NSQIP dataset. Training and validation cohorts were created. Pre-, intra-, and post-operative models to predict 30-day mortality were developed based on perioperative variables selected by stepwise cox regression analyses; model performance was assessed using AUC. RESULTS: Among 17,683 patients who underwent PD, 1.6% died within 30-days. Patient factors and events associated with 30-day mortality were incorporated into a risk calculator (https://ktsahara.shinyapps.io/Real-timePD/). The accuracy of the risk-calculator increased relative to hospital time-course in both the training (AUC, pre-:0.696, intra-:0.724, post-operative:0.871) and validation (AUC, pre-:0.681, intra-:0.702, post-operative:0.850) cohorts. One in 3 patients had a concordant calculated risk of mortality using pre-versus postoperative variables to inform the risk model (kappa = 0.474). CONCLUSION: Risk of mortality fluctuated over the hospital course following PD and preoperative risk assessment was often discordant with risk assessed at other periods. The proposed "real-time" calculator may help better stratify patients with increased risk of 30-day mortality.


Assuntos
Hospitalização , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
5.
World J Surg ; 45(12): 3643-3651, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34379172

RESUMO

BACKGROUND: Pancreatectomy is the main curative therapeutic option for pancreatic neuroendocrine tumors (pNETs). Given the indolent behavior of pNETs and the relatively limited lifetime of elderly patients, the impact of primary site surgery (PSS) of pNETs on long-term outcomes among older patients has been a topic of debate. METHODS: Patients aged 70 or older with pNETs were identified in the Surveillance, Epidemiology and the End Results (SEER) database from 1998 to 2016. Propensity score matching was used to compare overall (OS) and cancer-specific survival (CSS) of patients who did versus did not undergo PSS. RESULTS: Among 2,319 elderly patients with pNETs, 942 patients (40.6%) underwent PSS, while 1,377 (59.4%) did not undergo PSS (non-PSS: NPSS). After propensity score matching (n = 433 in each group), PSS group had improved survival compared with the NPSS group (5-year OS: 53.4% vs. 37.3%; 5-year CSS: 77.2% vs. 58.1%, both p < 0.001). In contrast, subgroup analysis of individuals aged ≥ 80 revealed no difference in 5-year CSS (PSS: 69.2% vs. NPSS: 67.4%, p = 0.27). A subgroup analysis among patients who had small (≤ 2 cm) non-functional (NF) pNETs noted comparable long-term outcomes among patients who underwent PSS versus NPSS patients (5-year OS: 73.1% vs. 66.5%, p = 0.19; 5-year CSS: 98.5% vs. 95.2%, p = 0.14). CONCLUSIONS: Approximately 2 in 5 elderly patients with pNETs underwent PSS. While PSS was generally associated with prolonged OS and CSS among older patients, PSS was not associated with improved CSS among a subset of patients aged 80 or older, as well as among patients age ≥ 70 years with NF-pNET less than 2 cm.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Idoso , Idoso de 80 Anos ou mais , Humanos , Tumores Neuroendócrinos/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos
6.
J Org Chem ; 85(7): 5109-5113, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138515

RESUMO

The addition of methanesulfonic acid to N-(2,6-dimethylpyridin-4-yl)-N-methyl-2-iso-propylaniline led to the selective protonation of the pyridine nitrogen atom, resulting in a significant deceleration of the rotation rates around both N-pyridyl and N-(i-Pr)phenyl bonds through a relayed brake mechanism.

7.
Ann Surg Oncol ; 26(13): 4506-4514, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31489551

RESUMO

BACKGROUND: Peritoneal dissemination is one of the major recurrence patterns in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with poor prognosis. Here, we assessed the diagnostic potential of microRNA (miRNA) profiles in peritoneal washings for prediction of peritoneal dissemination in PDAC. PATIENTS AND METHODS: From January 2016 to July 2017, peritoneal washings were obtained prospectively from 59 patients with PDAC undergoing surgery the Yokohama City University Hospital. MiRNA expression was evaluated by Agilent human miRNA microarray and quantitative reverse-transcription polymerase chain reaction. RESULTS: Microarray analysis identified upregulated and downregulated miRNAs in peritoneal washings of patients with peritoneal dissemination. We validated four miRNAs (miR-141-3p, miR-194-3p, miR-194-5p, and miR-200c-3p) with high expression in peritoneal washings. The cumulative incidence rate of peritoneal recurrence in peritoneal cytology-negative patients in the miR-194-5p high group was significantly higher than that in the miR-194-5p low group (p = 0.002). Univariate and multivariate analyses revealed that high miR-194-5p was associated with overall survival (OS). CONCLUSIONS: High expression of miR-194-5p in peritoneal washings is associated with peritoneal recurrence and poor OS in patients with peritoneal cytology-negative PDAC.


Assuntos
Carcinoma Ductal Pancreático/patologia , MicroRNAs/análise , Neoplasias Pancreáticas/patologia , Lavagem Peritoneal , Idoso , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/mortalidade , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Neoplasias Pancreáticas
8.
Surg Endosc ; 33(11): 3851-3857, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31183798

RESUMO

BACKGROUND: In our process of standardizing laparoscopic right-sided anatomical hepatectomy, we found several advantages of the caudate lobe-first approach. We herein describe our standardized procedure of laparoscopic right posterior sectionectomy (Lap-RPS) using this approach. METHODS: Between January 2011 and January 2018, 31 patients underwent pure Lap-RPS in our hospital. The mean patient age was 68 years (range 47-85 years), and the number of male patients was more than that of female patients (64.5%). Of 31 patients, 20 had metastatic liver tumor, 7 had hepatocellular carcinoma, 3 had intrahepatic cholangiocellular carcinoma, and 1 had hemangioma. All 31 patients had Child-Pugh class A liver function. The surgical technique was recorded on video. Cumulative sum (CUSUM) analyses were applied to assess the learning curve. RESULTS: The mean operative time was 420 min (range 263-639 min), and the mean amount of blood loss was 304 g (range 10-900 g). No procedure was converted to open surgery. Postoperative bleeding, bile leakage, hepatic failure, and mortality did not occur. CUSUM analyses showed a decrease in the operative time and blood loss after using the caudate lobe-first approach. CONCLUSION: Our standardized procedure of Lap-RPS using the caudate lobe-first approach is not only feasible but also expected to provide an advantage for laparoscopic anatomical hepatectomy.


Assuntos
Carcinoma Hepatocelular , Colangiocarcinoma , Hemangioma , Hepatectomia/métodos , Neoplasias Hepáticas , Fígado , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Hemangioma/patologia , Hemangioma/cirurgia , Humanos , Laparoscopia/métodos , Curva de Aprendizado , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Estadiamento de Neoplasias
9.
World J Surg ; 43(12): 3153-3160, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31549202

RESUMO

BACKGROUND: Increasing evidence suggests that cancer-associated inflammation, as indicated by markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow Prognostic Score (mGPS), predicts poor outcomes in pancreatic cancer. In this study, the associations between systemic inflammation markers and survival were examined in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) patients who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection. METHODS: From April 2009 to December 2017, 119 patients diagnosed with BR-PDAC and receiving NACRT followed by radical surgery were included in this retrospective study. The associations between the pre- and post-NACRT NLR, PLR, mGPS, and clinicopathological characteristics, as well as their predictive values for survival outcomes, were analyzed. This study was approved by an institutional review board at Yokohama City University (B180600049). RESULTS: On multivariate analysis with a Cox's proportional hazards regression model, post-NACRT NLR ≥3 (p = 0.040; hazard ratio, 2.24; 95% CI 1.28-3.91) and lymph node metastasis (p = 0.002; hazard ratio, 2.33; 95% CI 1.36-3.99) were significantly associated with shorter overall survival. The median survival time was 22.0 months for patients with post-NACRT NLR ≥3 and 45.0 months for patients with post-NACRT NLR <3 (p = 0.028). CONCLUSIONS: The NLR following NACRT might predict survival in BR-PDAC patients. Patients with an elevated post-NACRT NLR or positive lymph node metastasis may be candidates for stronger adjuvant therapies.


Assuntos
Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia , Linfócitos , Neutrófilos , Neoplasias Pancreáticas/terapia , Adenocarcinoma/mortalidade , Idoso , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos
10.
World J Surg Oncol ; 17(1): 140, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399104

RESUMO

BACKGROUND: Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied. METHODS: Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining. RESULTS: A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy. CONCLUSIONS: High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy.


Assuntos
Adenocarcinoma/mortalidade , Ampola Hepatopancreática/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Ducto Colédoco/mortalidade , Proteína HMGB1/metabolismo , Pancreaticoduodenectomia/mortalidade , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/metabolismo , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Cell Biochem ; 119(1): 634-639, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28628234

RESUMO

The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8+ tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8+ TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 107 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P < 0.01). Hematoxylin and easin (H&E) staining on tumor sections was performed to evaluate tumor destruction which was classified according to the Evans grading system and found to be much greater in the S. typhimurium A1-R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P < 0.01). Immunohistochemical staining with anti-mouse CD8+ antibody was performed in order to detect TILs determined by calculating the average number of CD8+ cells in three high power fields (200×) in the treated and untreated tumors. The TIL score was significantly higher in G2 (133.5 ± 32.2) than G1 (45.1 ± 19.4, P < 0.001). The present study demonstrates that S. typhimurium A1-R promotes CD8+ T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Adenocarcinoma/terapia , Linfócitos T CD8-Positivos/imunologia , Imunidade Celular , Imunoterapia , Neoplasias Experimentais/terapia , Neoplasias Pancreáticas/terapia , Salmonella typhimurium/imunologia , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Linfócitos T CD8-Positivos/patologia , Camundongos , Camundongos Nus , Metástase Neoplásica , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia
12.
Aesthetic Plast Surg ; 42(2): 442-446, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29101435

RESUMO

We describe a new wound management technique using a soft dressing material to stabilize the areola skin graft and protect the nipple after nipple-areola reconstruction at the final stage of breast reconstruction. We introduced a center-fenestrated multilayered hydrocellular polyurethane foam dressing material that provides adequate pressure and retains a moist environment for a smooth skin graft "take." Moreover, the reconstructed nipple can be monitored at any time through the fenestrated window for adequate blood circulation. Altogether, this simple and inexpensive wound dressing technique improves the clinical outcome. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Bandagens , Mamoplastia/métodos , Mamilos/cirurgia , Poliuretanos , Retalhos Cirúrgicos/transplante , Cicatrização/fisiologia , Adulto , Neoplasias da Mama/cirurgia , Estudos de Coortes , Estética , Feminino , Humanos , Japão , Mastectomia/métodos , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Estudos Retrospectivos
14.
J Surg Res ; 220: 391-401, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29180208

RESUMO

BACKGROUND: A high accumulation of CD8+ tumor-infiltrating lymphocytes (TILs) induced by neoadjuvant chemoradiotherapy (NACRT) is associated with a favorable prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the correlation between a high accumulation of CD8+ TILs and a favorable prognosis has yet to be fully clarified. The aim of this study was to determine predictive markers of a high accumulation of CD8+ TILs, with a favorable prognosis, using proteomic analysis. MATERIALS AND METHODS: We studied 72 resected borderline resectable PDAC patients treated with NACRT between April 2009 and March 2014. Three matched pairs of high CD8+ TIL patients with a favorable prognosis and low CD8+ TIL patients with a poor prognosis were selected. Shotgun proteomics of the stroma and cancerous lesion was performed using formalin-fixed, paraffin-embedded tissue. Validation of the identified proteins was performed using immunohistochemical staining. Relationships between the identified proteins and TILs and clinical outcomes were assessed. RESULTS: Marginal zone B- and B1-cell-specific protein (MZB1) was detected in the tumor stroma. MZB1 expression was positively correlated with a high accumulation of CD8+ TILs. High stromal MZB1 expression also correlated with disease-free and overall survival. In a subgroup analysis of CD8+ expression, there was a significant association between stromal MZB1 expression and disease-free and overall survival in the high CD8+ TIL group. CONCLUSIONS: MZB1 is a potential marker of a high accumulation of CD8+ TILs in borderline resectable PDACs resected after NACRT. Combination of CD8+ TILs with MZB1 may be a new biomarker of resected cases after NACRT.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma Ductal Pancreático/metabolismo , Citocinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Biomarcadores/metabolismo , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Proteômica
15.
J Surg Oncol ; 116(3): 416-426, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28608409

RESUMO

BACKGROUND: Damage-associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor-infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. METHODS: NACRT was administered to 51 patients with borderline-resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer. Resected specimens were analyzed for the presence of DAMPs, major histocompatibility complex class I-related chain A/B (MICA/B), and CD8+ TILs, CD4+ TILs, and forkhead box P3 positive (Foxp3+ ) TILs. The Treg/TIL ratio was obtained by dividing the number of Foxp3+ TILs, a surrogate for regulatory T cells, by the sum of CD8+ and CD4+ TILs. RESULTS: Overexpression of calreticulin, Hsp70, and MICA/B were all significantly correlated with NACRT administration. In the NACRT group, high MICA/B expression was associated with a low Treg/TIL ratio, indicating a favorable immunogenic tumor microenvironment. Patients with a lower Treg/TIL ratio had longer survival. CONCLUSIONS: Overexpression of MICA/B, a component of DAMPs induced by NACRT, may play an important role in acquiring a favorable immune response for pancreatic cancer which contributes to longer survival, suggesting the potential of immunotherapy of this recalcitrant disease, especially for patients with overexpression of DAMPs.


Assuntos
Quimiorradioterapia , Antígenos de Histocompatibilidade Classe I/metabolismo , Terapia Neoadjuvante , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Idoso , Alarminas/metabolismo , Feminino , Humanos , Linfócitos do Interstício Tumoral/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microambiente Tumoral
16.
Ann Surg Oncol ; 23(Suppl 4): 475-484, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27387681

RESUMO

PURPOSE: The aim of this study was to assess the efficacy of combined resection and reconstruction (CRR) of the hepatic artery (HA) in surgery for hilar cholangiocarcinoma (HC). MATERIALS AND METHOD: Among 172 patients who underwent surgical resection for HC, the following three groups were defined according to the type of vascular reconstruction: VR(-) group, in which neither CRR of the portal vein (PV) nor HA was performed (n = 74); VR-PV group, in which only CRR of the PV was required (n = 54); and VR-A group, in which CRR of the HA was performed either with or without CRR of the PV (n = 44). Clinicopathological variables and clinical outcomes were compared among the three groups. RESULTS: Although the VR-A group showed significantly more advanced disease than other groups, the R0 resection rate was comparable among the three groups (VR(-), 74 %; VR-PV, 80 %; VR-A, 80 %). The 5-year disease-specific survival rate was also comparable among the three groups (VR(-), 45.6 %; VR-PV, 51.2 %; VR-A, 22.3 %), but tended to be worse in the VR-A group than in the other groups. A similar trend was observed in morbidity rate. Lymph node metastasis was more frequent in the VR-A group (59 %) than in the other groups (VR(-), 33.8 %; VR-PV, 50 %). In the VR-A group, lymph node metastasis (p = 0.004) and adjuvant chemotherapy (p = 0.006) were determined to represent independent prognostic factors for survival according to multivariate analysis. CONCLUSION: CRR of the HA was considered efficacious in selected patients; however, long-term outcomes of the VR-A group seem unsatisfactory. Treatments additional to surgery may be necessary in cases requiring CRR of the HA.

17.
Gan To Kagaku Ryoho ; 43(10): 1166-1170, 2016 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-27760934

RESUMO

BACKGROUND: Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. METHODS: Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled. The NACRT comprised radiotherapy( 1.8 Gy×28 days)and full-dose twice-daily oral S-1 given on the same days as the radiotherapy. The results of the NACRT and pancreatectomy and the patients' prognoses were evaluated. RESULTS: Fifty-five patients(69.6%)underwent pancreatectomy, with no case of mortality. The curative resection rate was 94.5%. Postoperative adjuvant chemotherapy was administered in 46 patients(83.6%). The 3-year survival rates of all 79 patients and 55 pancreatectomy patients were 40.1% and 50.4%, respectively. CONCLUSION: NACRT using S-1 was found to be feasible, and good mid-term outcomes were obtained. However, analysis of the long-term outcomes and comparisons with other novel anti-cancer drugs are still required.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Terapia Neoadjuvante , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/terapia , Tegafur/uso terapêutico , Quimiorradioterapia , Combinação de Medicamentos , Humanos , Pancreatectomia , Prognóstico
19.
Ann Surg Oncol ; 22(1): 180-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25120248

RESUMO

BACKGROUND: The tumor-infiltrating lymphocyte (TIL) count in several types of cancer, including colorectal cancer and colorectal liver metastases (CRLM), reportedly predicts survival following resection; however, the prognostic significance of the TIL counts remains controversial. METHODS: In total, 162 patients who underwent potentially curative resection for CRLM from 1992 to 2010 were immunohistochemically analyzed retrospectively. CD4, CD8, and FoxP3 were examined as markers for helper T cells, cytotoxic T cells, and regulatory T cells (Tregs), respectively. The correlation between patients' TIL composition and long-term outcome was investigated. RESULTS: The median follow-up time was 46.6 months for all patients and 46.8 months for survivors. Cancer-specific survival (CSS) at 1, 3, and 5 years was 93.2, 65.6, and 51.0 %, respectively. The 5-year disease-free survival and CSS among patients with high infiltration of peritumoral Tregs was 44.2 and 74.8 %, respectively, while those of patients with low infiltration of peritumoral Tregs was 18.9 and 40.3 %, respectively (p < 0.01 for both). Multivariate analyses indicated that synchronous liver metastases, hypoalbuminemia, and low peritumoral Treg infiltration were significant predictors of unfavorable CSS. CONCLUSIONS: Low peritumoral Treg infiltration proved to be a significant predictor of unfavorable CSS in patients undergoing resection for CRLM.


Assuntos
Neoplasias Colorretais/imunologia , Hepatectomia/mortalidade , Neoplasias Hepáticas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Fatores de Transcrição Forkhead/metabolismo , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Gan To Kagaku Ryoho ; 42(3): 379-82, 2015 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-25812513

RESUMO

We report 3 cases of long-term control achieved via S-1 monotherapy in elderly patients with advanced non-small-cell lung cancer. In case 1, a 75-year-old man clinically diagnosed with stage IIIA lung adenocarcinoma received S-1 as fourthline chemotherapy. PR was achieved, and PFS was 8 months. In case 2, a 78-year-old woman clinically diagnosed with stage IV lung squamous cell carcinoma received S-1 as third-line chemotherapy. A PR was achieved, and PFS was 14 months. In case 3, an 83-year-old man clinically diagnosed with stage IV lung squamous cell carcinoma received CBDCA plus PTX, followed by S-1 on alternate days. Although tumor size was not reduced, SD was maintained for 11 months.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
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