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1.
Front Oncol ; 12: 950418, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387243

RESUMO

Background: Peritoneal sarcomatosis (PS) could occur in patients with retroperitoneal sarcomas (RPS). This study aimed to expand the understanding of PS on its characteristics and prognostic role, and develop a nomogram to predict its occurrence preoperatively. Methods: Data of 211 consecutive patients with RPS who underwent surgical treatment between 2011 and 2019 was retrospectively reviewed. First, the clinicopathological characteristics of PS were summarized and analyzed. Second, the disease-specific survival (DSS) and recurrence-free survival (RFS) of patients were analyzed to evaluate the prognostic role of PS. Third, preoperative imaging, nearly the only way to detect PS preoperatively, was combined with other screened risk factors to develop a nomogram. The performance of the nomogram was assessed. Results: Among the 211 patients, 49 (23.2%) patients had PS with an incidence of 13.0% in the primary patients and 35.4% in the recurrent patients. The highest incidence of PS occurred in dedifferentiated liposarcoma (25.3%) and undifferentiated pleomorphic sarcoma (25.0%). The diagnostic sensitivity of the preoperative imaging was 71.4% and its specificity was 92.6%. The maximum standardized uptake value (SUVmax) was elevated in patients with PS (P<0.001). IHC staining for liposarcoma revealed that the expression of VEGFR-2 was significantly higher in the PS group than that in the non-PS group (P = 0.008). Survival analysis (n =196) showed significantly worse DSS in the PS group than in non-PS group (median: 16.0 months vs. not reached, P < 0.001). In addition, PS was proven as one of the most significant prognostic predictors of both DSS and RFS by random survival forest algorithm. A nomogram to predict PS status was developed based on preoperative imaging combined with four risk factors including the presentation status (primary vs. recurrent), ascites, SUVmax, and tumor size. The nomogram significantly improved the diagnostic sensitivity compared to preoperative imaging alone (44/49, 89.8% vs. 35/49, 71.4%). The C-statistics of the nomogram was 0.932, and similar C-statistics (0.886) was achieved at internal cross-validation. Conclusion: PS is a significant prognostic indicator for RPS, and it occurs more often in recurrent RPS and in RPS with higher malignant tendency. The proposed nomogram is effective to predict PS preoperatively.

2.
J Surg Oncol ; 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36444482

RESUMO

BACKGROUND AND OBJECTIVES: Resection of retroperitoneal sarcoma (RPS) en bloc with pancreas is challenging and controversial. This single-center retrospective study aimed to analyze the impact of pancreatic resection (PR) and its different types on short- and long-term outcomes in patients with RPS. METHODS: Data from 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were analyzed. Out of these, 90 patients underwent PR, including pancreaticoduodenectomy (PD) in 31 and distal pancreatectomy (DP) in 59. RESULTS: Patients in the PR group had a higher major morbidity (37.8% vs. 14.5%) and mortality (8.9% vs. 1.3%) than those in the non-PR group, with a similar 5-year overall survival (OS) rate (46.9% vs. 53.6%). Patients in the PD and DP groups had a slight difference in major morbidity (48.4% vs. 32.2%), mortality (6.4% vs. 10.2%), and 5-year OS rates (43.3% vs. 49.3%). The PR type was not an independent risk factor for major morbidity or OS. CONCLUSIONS: PR in RPS resection was associated with increased morbidity and mortality with minimal influence on survival. Patients with RPS undergoing PD and DP showed slight differences in terms of safety and OS.

3.
Front Surg ; 9: 956384, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157408

RESUMO

The outcomes of patients with primary retroperitoneal sarcoma (RPS) are significantly superior to those with recurrence. En bloc resection of tumor and adjacent organs is recommended in primary RPS. However, whether en bloc resection of tumor and adjacent organs can benefit recurrent patients or some recurrent patients is unclear. We compared the outcomes of patients with primary RPS, first recurrence (RPS-Rec1), and ≥2 recurrences (≥RPS-Rec2) to evaluate the value and criteria for en bloc resection of tumor and adjacent organs in recurrent cases. We evaluated the safety of en bloc resection of tumor and adjacent organs by assessing operation time, blood loss volume, postoperative morbidities (POM), and efficacy by comparing local recurrence and peritoneal metastasis (LR-PM), distant metastasis, progression-free survival (PFS), and overall survival (OS). A total of 101, 47, and 30 patients with primary RPS, RPS-Rec1, and ≥RPS-Rec2 were included, respectively. Recurrent RPS invaded more adjacent organs and surrounding fat tissue than primary RPS. The operation time, amount of blood loss, incidence of grade III-V POM, LR-PM rate, PFS, and OS in the RPS-Rec1 group were similar to those of the primary group, both of which were significantly superior to those of the ≥RPS-Rec2 group. Macroscopically incomplete resection and high-grade RPS rather than first recurrence were independent risk factors for LR-PM, PFS, and OS. In conclusion, the safety and efficacy of en bloc resection of tumor and adjacent organs in RPS-Rec1 were comparable with those in primary RPS but significantly superior to those of ≥RPS-Rec2. For RPS-Rec1, comparable outcomes to patients with primary RPS can be achieved, particularly in those in whom a macroscopically complete resection is achieved.

4.
J Surg Oncol ; 126(7): 1288-1298, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35943840

RESUMO

BACKGROUND AND OBJECTIVES: Retroperitoneal sarcomas (RPSs) are difficult to manage, rare malignant tumors. This single-center, retrospective study aimed to analyze the treatment algorithm and outcomes of aggressive surgical treatment in patients with primary and recurrent RPS. METHODS: Data of 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were collected and analyzed. Indications for surgery were based on the treatment algorithm. RESULTS: A total of 145 patients with primary RPS and 97 with recurrent RPS were included. The recurrent cohort comprised more patients with multifocal tumors than the primary cohort (64.9% vs. 15.2%). R0/R1 resection was achieved in 94.5% and 81.4% of the primary and recurrent RPS cases, respectively. Major complication rates in the primary and recurrent cohorts were 17.9% and 30.9%, respectively. During a median follow-up of 51 months, the estimated 5-year overall survival, local recurrence, and distant metastasis rates for patients with primary and recurrent RPS were 61.0% versus 37.1%, 47.4% versus 71.3%, and 18.4% versus 17.6%, respectively. CONCLUSIONS: Aggressive surgical treatment achieved good local control and long-term survival in patients with primary RPS, whereas the prognosis in patients with recurrence were significantly worse.


Assuntos
Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Algoritmos , Recidiva Local de Neoplasia/patologia , Neoplasias Retroperitoneais/patologia , Estudos Retrospectivos , Sarcoma/patologia , Taxa de Sobrevida , Resultado do Tratamento , Tomada de Decisão Clínica
5.
Mol Med Rep ; 25(2)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35014686

RESUMO

Long non­coding RNAs can regulate the malignant tumor phenotype either as tumor suppressors or oncogenes. The present study investigated the underlying mechanism of LINC00238 in liver cancer. LINC00238 was identified as a downregulated molecule in The Cancer Genome Atlas liver hepatocellular carcinoma dataset through Gene Expression Profiling Interactive Analysis software. Through gain­ and loss­of­function experiments, LINC00238 was confirmed as a tumor suppressor that could not only decrease cell viability, migration and invasion in vitro, but also tumorigenesis and tumor metastasis in vivo. By cytoplasmic and nuclear RNA isolation, LINC00238 was confirmed to be predominantly cytoplasmic. Mechanistically, RNA pull­down assays showed that LINC00238 sponged microRNA (miR)­522 and then reversed the inhibitory effects on two downstream targets, secreted frizzled related protein 2 and dickkopf1. Collectively, LINC00238 was identified as a tumor suppressor that acts via sponging miR­522 followed by silencing of downstream targets, suggesting that LINC00238 may have a key role in suppressing the malignant phenotype of liver cancer cells.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Carcinogênese/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Galinhas , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Modelos Biológicos , Fenótipo , Prognóstico
6.
Updates Surg ; 74(3): 1157-1163, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32602011

RESUMO

Complete resection for retroperitoneal sarcoma (RPS) involving major vessels frequently requires vascular resection and reconstruction. The use of artificial grafts often leads to postoperative vascular graft infection (VGI), which usually requires reoperation and sometimes leads to death. In the present study, the data of RPS patients who underwent contralateral iliac artery (IIA) transposition for reconstruction of the common iliac artery (CIA) after RPS resection from 2015-2019 were retrospectively analyzed. Clinical, intraoperative, and postoperative outcomes were described. Contralateral IIA transposition was performed to reconstruct the CIA after segmental resection in three patients. All patients underwent concomitant organ resection. Colon resection was performed for all patients, nephrectomy was performed for two patients, and segmental resection of the left ureter with transurethral ureterostomy was performed for one patient. Complete resection was achieved in all patients, and microscopic tumor infiltration to the CIA was observed in all patients (tunica adventitia: 2, tunica media: 1). No major complications occurred during the hospital stay. During the follow-up period (6.0-29.1 months), one patient died from tumor recurrence, and the other two patients did not have any evidence of recurrence or metastatic disease at the latest follow-up. The level of lower limb function was favorable (MSTS93 scores: 28-30). The pelvic organ functions, including bowel, bladder, and sexual functions, were not impaired in any of the patients. This novel technique in which contralateral IIA transposition is performed to reconstruct the CIA after RPS resection is simple and reliable and may be a good alternative to artificial grafts.


Assuntos
Implante de Prótese Vascular , Neoplasias Retroperitoneais , Sarcoma , Aorta Abdominal/cirurgia , Implante de Prótese Vascular/métodos , Humanos , Artéria Ilíaca/cirurgia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/cirurgia , Stents , Resultado do Tratamento
7.
J Nucl Med ; 63(4): 556-559, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34475235

RESUMO

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Anticorpos Monoclonais , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Artéria Hepática/patologia , Humanos , Radioisótopos do Iodo , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia , Estudos Prospectivos , Resultado do Tratamento
8.
Abdom Radiol (NY) ; 47(9): 3217-3228, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34800159

RESUMO

PURPOSE: To evaluate the potential role of MR findings and DWI parameters in predicting small regional lymph nodes metastases (with short-axis diameter < 10 mm) in pancreatic ductal adenocarcinomas (PDACs). METHODS: A total of 127 patients, 82 in training group and 45 in testing group, with histopathologically diagnosed PDACs who underwent pancreatectomy were retrospectively analyzed. PDACs were divided into two groups of positive and negative lymph node metastases (LNM) based on the pathological results. Pancreatic cancer characteristics, short axis of largest lymph node, and DWI parameters of PDACs were evaluated. RESULTS: Univariate and multivariate analyses showed that extrapancreatic distance of tumor invasion, short-axis diameter of the largest lymph node, and mean diffusivity of tumor were independently associated with small LNM in patients with PDACs. The combining MRI diagnostic model yielded AUCs of 0.836 and 0.873, and accuracies of 81.7% and 80% in the training and testing groups. The AUC of the MRI model for predicting LNM was higher than that of subjective MRI diagnosis in the training group (rater 1, P = 0.01; rater 2, 0.008) and in a testing group (rater 1, P = 0.036; rater 2, 0.024). Comparing the subjective diagnosis, the error rate of the MRI model was decreased. The defined LNM-positive group by the MRI model showed significantly inferior overall survival compared to the negative group (P = 0.006). CONCLUSIONS: The MRI model showed excellent performance for individualized and noninvasive prediction of small regional LNM in PDACs. It may be used to identify PDACs with small LNM and contribute to determining an appropriate treatment strategy for PDACs.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos
9.
Front Oncol ; 12: 1040833, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36620578

RESUMO

Background: Retroperitoneal sarcomas (RPSs) located in the lower abdominal quadrants involving iliac vessels are difficult to manage. This study introduced a 5-step method for en bloc resection with graft interposition using the abdominoinguinal approach and evaluated its efficacy and safety. Methods: Data of 24 consecutive patients who met the inclusion criteria from 272 patients with RPS who underwent surgical treatment between April 2015 and April 2022 were retrospectively collected and analyzed. Results: The patients underwent left- or right-sided abdominoinguinal incision. In all patients, the abdominoinguinal approach provided good exposure, and complete resection was achieved. Iliac artery+vein, vein, and artery resection and replacement by graft were performed in 70.8%, 25.0%, and 4.2% of patients, respectively. Additional resected organs mainly included the colon, ureter, bladder, kidney, and abdominal wall. The median number of organs resected was 5. In 37.5% of patients, reconstruction of the lower abdominal wall and inguinal ligament was performed using a mesh. Venous graft thrombosis occurred in 21.7% of patients, while no patient had pulmonary embolism or arterial occlusion. Major complications occurred in 20.8% of patients, and no 30-day mortality was observed. The estimated 5-year local recurrence and distant metastasis rates were 54.4% and 22.1%, respectively, with a median recurrence-free survival of 27 months. Conclusions: En bloc resection of RPS involving iliac vessels with graft interposition using the abdominoinguinal approach is feasible and advantageous. Good complete resection rate and safety can be achieved. The long-term survival benefit of this surgical approach should be verified by further large-scale prospective controlled studies.

10.
Cancer Manag Res ; 13: 6157-6167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34385843

RESUMO

BACKGROUND: Previous studies have shown that nutrition and systemic inflammation plays an essential role in the development of soft tissue sarcoma. However, few studies have explored the association of clinicopathologic features and local recurrence with nutritional and inflammatory markers in retroperitoneal liposarcoma (RPLS). This study sought to evaluate the prognostic value of the preoperative nutritional and inflammatory markers for local recurrence-free survival (LRFS) among surgical RPLS patients. METHODS: The study included 111 RPLS patients who underwent surgery between May 2010 and June 2019 at the Peking University Cancer Hospital Sarcoma Center. Time-dependent receiver operating characteristic (time-ROC) curve analysis was conducted to evaluate the ability of markers to predict LRFS. The associations of the CONUT-FAR score with clinicopathological variables and LRFS were evaluated. RESULTS: In the time-ROC curve analysis, the CONUT-FAR score was superior to other nutritional and inflammatory markers in predicting LRFS. The CONUT-FAR score was the only nutritional and inflammatory marker that independently predicted LRFS in the multivariate analysis, and patients with a high CONUT-FAR score (> 11) showed significantly decreased LRFS. Although the CONUT-FAR score failed to discriminate patients with low grade (G1) (p = 0.327) or undergoing incomplete (R2) resection (p = 0.072), it stratified patients with high grade (G2 and G3) or undergoing complete resection (R0/R1) into subgroups with significantly distinct LRFS (p < 0.001). The CONUT-FAR score also showed good clinical utility among patients with different clinical characteristics. CONCLUSION: The preoperative CONUT-FAR score reflects both nutritional and inflammatory factors and is an effective predictor of LRFS for surgical RPLS patients.

11.
Contrast Media Mol Imaging ; 2021: 7191363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505228

RESUMO

This study aimed to evaluate the usefulness of maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) in differentiating the subtypes and tumor grades of retroperitoneal liposarcoma (RPLS). The data of RPLS patients who underwent surgical resection from November 2013 to December 2019 at the sarcoma center of our institute were reviewed. The demographics, clinical features, and SUVmax of 84 patients who underwent preoperative 18F-FDG PET/CT scans were analyzed. Of these, 19 patients (22.6%) were with well-differentiated liposarcoma (WDLPS), 60 patients (71.4%) were with dedifferentiated liposarcoma (DDLPS), and 5 patients (6.0%) were with pleomorphic liposarcoma (PMLPS). The median SUVmax of WDLPS, DDLPS, and PMLPS groups was 2.8 (IQR: 1.9-3.2), 6.2 (IQR: 4.1-11.3), and 4.5 (IQR: 4.0-7.4). The ROC curve suggested 3.8 as an approximate cutoff value of SUVmax for distinguishing WDLPS and non-WDLPS (sensitivity = 0.769; specificity = 0.895). The median SUVmax for FNCLCC Grades 1, 2, and 3 of RPLS was 2.5 (IQR: 1.9-3.2), 4.5 (IQR: 3.2-6.7), and 9.0 (IQR: 6.0-13.3). The ROC curves suggest that SUVmax of ≤3.8 and >5.3 can be used for predicting FNCLCC Grades 1 and 3, respectively. The result showed that 18F-FDG PET/CT exhibited high sensitivity and specificity for identifying the subtypes and FNCLCC grades of RPLS. Additionally, 18F-FDG PET/CT might be a useful complementary imaging modality for guiding suitable biopsy location of RPLS.


Assuntos
Lipossarcoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Retroperitoneais/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Lipossarcoma/diagnóstico , Lipossarcoma/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/patologia
12.
Int J Med Sci ; 17(18): 3073-3081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173428

RESUMO

Patient-derived xenograft (PDX) models are effective preclinical cancer models that reproduce the tumor microenvironment of the human body. The methods have been widely used for drug screening, biomarker development, co-clinical trials, and personalized medicine. However, the low success rate and the long tumorigenesis period have largely limited their usage. In the present studies, we compared the PDX establishment between hepatocellular cancer (HCC) and metastatic liver cancer (MLC), and identified the key factors affecting the transplantation rate of PDXs. Surgically resected tumor specimens obtained from patients were subcutaneously inoculated into immunodeficient mice to construct PDX models. The overall transplantation rate was 38.5% (20/52), with the HCC group (28.1%, 9/32) being lower than MLC group (56.2%, 9/16). In addition, HCC group took significantly longer latency period than MLC group to construct PDX models. Hematoxylin and eosin staining results showed that the histopathology of all generations in PDX models was similar to the original tumor in all three types of cancer. The transplantation rate of PDX models in HCC patients was significantly associated with blood type (P=0.001), TNM stage (P=0.023), lymph node metastasis (P=0.042) and peripheral blood CA19-9 level (P=0.049), while the transplantation rate of PDX models in MLC patients was significantly associated with tumor size (P=0.034). This study demonstrates that PDX models can effectively reproduce the histological patterns of human tumors. The transplantation rate depends on the type of original tumor. Furthermore, it shows that the invasiveness of the original liver cancer affects the possibility of its growth in immunodeficient mice.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Fígado/patologia , Microambiente Tumoral , Animais , Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Camundongos , Pessoa de Meia-Idade , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
13.
Front Oncol ; 10: 548789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072576

RESUMO

BACKGROUND: En bloc resection of retroperitoneal sarcoma (RPS) with adjacent organs such as pancreatic head and duodenum is challenging for surgeons. This mono-institutional study aims to evaluate the feasibility, safety, and outcome of performing pancreaticoduodenectomy (PD) during RPS resection. METHODS: The clinical data of RPS patients who underwent PD at the Sarcoma Center of Peking University Cancer Hospital from January 2011 to December 2019 was collected and analyzed. RESULTS: Twenty-seven patients out of a total of 264 surgically treated RPS underwent PD. The main pathological subtype was liposarcoma. All patients received concomitant resection of a median of three additional organs (range: 1-5), including 11 patients (40.7%) who underwent inferior vena cava resection and one patient who underwent segmental superior mesenteric-portal vein resection. Microscopic tumor infiltration to the duodenum or pancreas was observed in 81.5% of patients. Major complications occurred in 40.7% of patients; the reoperation rate was 22.2%. One patient (3.7%) died from liver abscess postoperatively. During a median follow-up of 18.9 months, 15 patients (55.6%) developed locally recurrent disease; two patients (7.4%) also had pulmonary metastases additionally. Twelve patients (44.4%) died from local relapse eventually. CONCLUSION: PD during RPS resection is feasible, and it may be necessary to achieve complete resection. However, considering the complexity and risk, it should be performed by an experienced surgical team. The long-term survival benefit of this procedure should be verified by further large-scale multi-institutional studies.

14.
Toxicol Appl Pharmacol ; 401: 115118, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32619553

RESUMO

Glucocorticoid receptor (GR) modulates extensive biological and pathological processes including tumor progression through diverse mechanisms. The regulatory effects of dexamethasone (DEX), a synthetic glucocorticoid, as well as its interaction with GR have been recognized beyond hematologic cancers. In the present study, we investigated the anti-cancer efficacy of DEX and the correlation with GR in pancreatic cancer, a most aggressive malignancy threatening human health. The differential levels of GR expression were examined in two human pancreatic cancer cell lines, PANC-1 and SW1990, as well as in xenografts and patient tumor tissues. DEX significantly inhibited colony formation, migration, and tumor growth of PANC-1 cells expressing abundant GR. The underlying mechanisms involved suppression of nuclear factor κB (NF-κB) phosphorylation and down-regulation of epithelial-to-mesenchymal transition (EMT), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF). The anti-cancer effects of DEX were partially reversed by GR silencing or combinational administration of GR antagonist, RU486. The dose-dependent efficacy of DEX in tumor growth inhibition was also demonstrated in a GR-positive patient-derived xenograft model along with safety in mice. DEX was less potent, however, in SW1990 cells with poor GR expression. Our findings suggest that DEX effectively inhibits pancreatic tumor growth partially through GR activation. The potential correlation between GR expression and anti-cancer efficacy of DEX may have some clinical implications.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Dexametasona/uso terapêutico , Neoplasias Pancreáticas/metabolismo , Receptores de Glucocorticoides/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Células A549 , Animais , Antineoplásicos Hormonais/farmacologia , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Carga Tumoral/fisiologia
15.
Am J Transl Res ; 11(5): 3128-3139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217882

RESUMO

Tumor samples of pancreatic ductal adenocarcinoma patients, who underwent resection surgery, were implanted into NOD/SCID mice to construct pancreatic cancer patient-derived xenograft (PDX) models and explore the biological changes in the different generations of PDXs. Ten PDXs were successfully generated, and the tumor formation rate of F1 PDXs was found to be 38.46%, which was lower than F2 (77.78%) and F3 (71.43%) PDXs. In addition, latent periods of tumorigenesis of F2 and F3 PDXs were significantly shorter, compared to that in F1 PDXs (P<0.05). Comparison of H&E staining of tumor tissue from primary pancreatic cancer and PDXs showed that all three generations of PDXs had similar histopathology to primary pancreatic cancer, indicating that PDXs may well reproduce the histological patterns of primary human cancer. Besides, Ki67 expression was increased in all three generations of PDXs compared to primary tumors of patients, and additionally, EpCAM expression was increased in F3 PDXs. These results were corroborated by the real-time qPCR and western blot results. Therefore, we concluded that PDXs are able to preserve the differentiation degree, morphological characteristics, and structural features of tumor cells. Furthermore, the latent periods of tumorigenesis are shortened after the first generation, which may be attributed to an increase in expression levels of tumor promoters such as Ki67 and EpCAM. PDX models may become an efficient tool for pancreatic cancer research.

16.
Pak J Pharm Sci ; 32(1(Special)): 459-464, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30852485

RESUMO

.To explore the clinicopathological features of solid pseudopapillary neoplasm (SPN) of pancreas and to analyze the related factors of SPNs with aggressive behavior. Clinical data of SPN patients admitted in the Single Center of Peking University Cancer Hospital from January 2007 to September 2017 were retrospectively analyzed. The correlations of clinicopathological features with aggressive SPNs and distant metastasis after curative resection were analyzed using univariate analysis. Twelve of the total 54 SPN patients were diagnosed as aggressive SPNs. Univariate analysis suggested clinical features had no correlations with aggressive SPNs. Patients were followed up for an average of 5.0 years, four of them developed distant metastases. Univariate analysis indicated that distant metastasis of SPNs was correlated with the aggressive behaviors (P=0.031). Moreover, vessels invasion (VI) and Ki-67>4% (P=0.012) were the independent risk factors of distant metastasis of SPNs. The aggressive SPNs, especially VI and Ki-67>4% are the independent factors correlated with distant metastases after SPNs surgery.


Assuntos
Carcinoma Papilar/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/cirurgia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
17.
Contrast Media Mol Imaging ; 2018: 2601281, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065620

RESUMO

Rationale: To assess the diagnostic value of 18F-FDG-PET/CT for different retroperitoneal soft tissue sarcomas (STS) and other similar tumors. To analyze the predictive value of 18F-FDG-PET/CT for histological grade and main prognostic factors. Methods: 195 patients with 44 different diseases have been included. Relationship between SUVmax, Clinical, pathological, and prognostic information has been analyzed. Results: Malignant tumors do not show higher SUVmax than benign ones (P=0.443). We divided all 44 different diseases into two groups; SUVmax of group 1 is significantly higher than group 2 (P ≤ 0.001). The ROC curve suggests 4.35 is the cutoff value to distinguish groups 1 and 2 (sensitivity = 0.789; specificity = 0.736). SUVmax correlates with Ki-67 index, mitotic count, vascular resection, histological grade, and recurrent STS without considering pathological diagnosis (P=0.001, P=0.012, P=0.002, P ≤ 0.001, and P=0.037, resp.). Conclusion: 18F-FDG-PET/CT cannot simply distinguish malignant and benign tumors in retroperitoneal/intra-abdominal cavity; however, the SUVmax of malignant tumors, inflammatory pseudotumor, and PPGL group is higher than the SUVmax of benign tumors, lymph node metastasis, hematoma, and low malignant STS group. Guidance of "SUVmax location" may be helpful for biopsy and pathology dissection.


Assuntos
Cavidade Abdominal/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Retroperitoneais/diagnóstico por imagem , Sarcoma/diagnóstico por imagem , Cavidade Abdominal/patologia , Diagnóstico Diferencial , Fluordesoxiglucose F18/farmacocinética , Humanos , Antígeno Ki-67/análise , Prognóstico , Sensibilidade e Especificidade
18.
J Gastrointest Surg ; 22(10): 1814-1818, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30039451

RESUMO

The precise intraoperative navigation of the surgical plane remains challenging in liver surgery; however, an innovative imaging technique-real-time virtual sonography (RVS)-may provide a solution. In this modality, preoperative three-dimensional (3D) resection simulation data are transmitted to an RVS workstation and can be used in combination with intraoperative ultrasound to navigate the surgical plane in real time. This paper describes this technique and our experiences in detail. From November 2015 to March 2017, 26 patients with primary liver cancer underwent liver resection under RVS navigation. The operative procedures employed included hemihepatectomy, bisegmentectomy, segmentectomy, and limited resection. RVS was utilized uneventfully and successfully in each operation. The median time required for spatial position registration was 3 (1-12) min, and as the case volume increased, the time required for registration markedly decreased. The surgical plane under RVS navigation was consistent with that of the preoperative plan, and the resection margin was confirmed negative in each case. In conclusion, RVS in combination with 3D simulation is a feasible, safe, and promising technique for the precise intraoperative navigation of liver resection for primary liver cancer. It could be applied to other resectable liver diseases and may be utilized in other centers.


Assuntos
Hepatectomia/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Cirurgia Assistida por Computador , Ultrassonografia/métodos , Adulto , Idoso , Simulação por Computador , Feminino , Humanos , Imageamento Tridimensional , Período Intraoperatório , Masculino , Margens de Excisão , Pessoa de Meia-Idade
19.
J Cancer Res Ther ; 14(4): 772-779, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29970651

RESUMO

AIM: The aim of this is study is to assess the efficacy and safety of conversion capecitabine plus oxaliplatin (XELOX) in Chinese patients with potentially resectable colorectal liver metastases (CLMs). PATIENTS AND METHODS: Thirty patients (median age 57.5 years) with potentially resectable CLMs were treated with XELOX in a single-arm, open-label, nonrandomized, multicenter clinical trial. RESULTS: The objective response rate in the 30 patients was 40% (95% confidence interval: 22.7%-59.4%), and the rate of conversion to resectable CLMs was 43.3%. Patients who underwent liver resection (n = 11) had a longer median progression-free survival and overall survival than those who did not. XELOX showed an acceptable safety profile. CONCLUSION: XELOX may effectively convert potentially resectable CLM into resectable CLM, providing survival benefits with a favorable safety profile. CLINICAL TRIALS.GOV IDENTIFIER: NCT 00997685.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Resultado do Tratamento
20.
Med Sci Monit ; 24: 961-969, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29449525

RESUMO

BACKGROUND There is no standard surgical approach for the management of retroperitoneal sarcoma. The aim of this clinical study was to describe the experience of an anterior approach to en bloc resection in left-sided retroperitoneal sarcoma with adjacent organ involvement. MATERIAL AND METHODS This retrospective clinical study included 25 patients who were diagnosed with left-sided retroperitoneal sarcoma and underwent tumor resection at a single center between May 2012 and July 2017. All patients had tumors that were adjacent to the left colon, pancreas, left kidney, left adrenal gland, and psoas major; some of the tumors were adjacent to the diaphragm, stomach, and small intestine. An anterior approach was used to remove the left-sided retroperitoneal tumor with the adhesive organs en bloc, an approach that is described in detail. The value of this surgical approach was evaluated based on the histopathological findings, postoperative complications, and patient follow-up. RESULTS The median number of resected organs, in addition to the retroperitoneal tumor, was 8 (range, 6-10). Complete macroscopic tumor resection was achieved in 23 cases (92%). Twenty-four patients (96%) had tumor infiltration of at least one organ or the surrounding fat. Three patients (12%) experienced Grade III and IV postoperative morbidities. The one-year disease-free survival rate was 91.3% among patients with macroscopically complete resections. The one-year overall survival rate was 83.2%. CONCLUSIONS In selected patients, left-sided retroperitoneal sarcoma associated with local organ involvement can be surgically managed using an anterior approach with en bloc resection of adjacent organs.


Assuntos
Especificidade de Órgãos , Neoplasias Retroperitoneais/cirurgia , Sarcoma/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/epidemiologia , Sarcoma/diagnóstico por imagem , Sarcoma/epidemiologia , Tomografia Computadorizada por Raios X
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