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1.
BMC Cancer ; 24(1): 828, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992597

RESUMO

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.


Assuntos
Tumores do Estroma Gastrointestinal , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-kit , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Sistema de Registros , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Feminino , Masculino , Taiwan/epidemiologia , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Sunitinibe/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Prognóstico , Idoso de 80 Anos ou mais , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Taxa de Sobrevida , Intervalo Livre de Progressão , Estimativa de Kaplan-Meier
2.
Surg Endosc ; 37(1): 148-155, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35879570

RESUMO

BACKGROUND: Omental wrapping (OW) is the leading cause of obstruction of the peritoneal dialysis (PD) catheter, which interferes with dialysis treatment. Routinely or selectively performing omentopexy during laparoscopic PD catheter placement has been suggested to prevent OW. However, most of the published techniques for performing this adjunctive procedure require additional incisions and suturing. Herein, we aimed to report our experience in performing omentopexy with a sutureless technique during dual-incision PD catheter insertion. We also performed a comparative analysis to assess the benefit/risk profile of routine omentopexy in these patients. METHODS: This retrospective study enrolled 469 patients who underwent laparoscopic PD catheter insertion. Their demographic characteristics and operative details were collected from the database of our institution. Omentopexy was performed by fixing the inferior edge of the omentum to the round ligament of the liver using titanium clips. For analysis, the patients were divided into the omentopexy group and the non-omentopexy group. We also reviewed the salvage management and outcomes of patients who experienced OW. RESULTS: The patients were categorized into the omentopexy (n = 81) and non-omentopexy (n = 388) groups. The patients in the non-omentopexy group had a higher incidence of OW, whereas no patient in the omentopexy group experienced this complication (5.2% vs. 0.0%, p = 0.033). The median operative time was 27 min longer in patients who underwent omentopexy than in those who did not [100 (82-118) min vs. 73 (63-84) min, p < 0.001]. One patient had an intra-abdominal hematoma after omentopexy and required salvage surgery to restore catheter function. The complication rate of omentopexy was 1.2% (1/81). CONCLUSION: Sutureless omentopexy during laparoscopic PD catheter insertion is a safe and reliable technique that does not require additional incisions and suturing. Routinely performing omentopexy provides clinical benefits by reducing the risk of catheter dysfunction due to OW.


Assuntos
Falência Renal Crônica , Laparoscopia , Diálise Peritoneal , Feminino , Humanos , Omento/cirurgia , Estudos Retrospectivos , Diálise Peritoneal/métodos , Catéteres , Laparoscopia/métodos , Falência Renal Crônica/cirurgia , Cateteres de Demora
3.
Medicina (Kaunas) ; 59(6)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37374218

RESUMO

Background and Objectives: In peritoneal dialysis (PD) therapy, intra-abdominal adhesions (IAAs) can cause catheter insertion failure, poor dialysis function, and decreased PD adequacy. Unfortunately, IAAs are not readily visible to currently available imaging methods. The laparoscopic approach for inserting PD catheters enables direct visualization of IAAs and simultaneously performs adhesiolysis. However, a limited number of studies have investigated the benefit/risk profile of laparoscopic adhesiolysis in patients receiving PD catheter placement. This retrospective study aimed to address this issue. Materials and Methods: This study enrolled 440 patients who received laparoscopic PD catheter insertion at our hospital between January 2013 and May 2020. Adhesiolysis was performed in all cases with IAA identified via laparoscopy. We retrospectively reviewed data, including clinical characteristics, operative details, and PD-related clinical outcomes. Results: These patients were classified into the adhesiolysis group (n = 47) and the non-IAA group (n = 393). The clinical characteristics and operative details had no remarkable between-group differences, except the percentage of prior abdominal operation history was higher and the median operative time was longer in the adhesiolysis group. PD-related clinical outcomes, including incidence rate of mechanical obstruction, PD adequacy (Kt/V urea and weekly creatinine clearance), and overall catheter survival, were all comparable between the adhesiolysis and non-IAA groups. None of the patients in the adhesiolysis group suffered adhesiolysis-related complications. Conclusions: Laparoscopic adhesiolysis in patients with IAA confers clinical benefits in achieving PD-related outcomes comparable to those without IAA. It is a safe and reasonable approach. Our findings provide new evidence to support the benefits of this laparoscopic approach, especially in patients with a risk of IAAs.


Assuntos
Laparoscopia , Diálise Peritoneal , Humanos , Estudos Retrospectivos , Cateteres de Demora , Diálise Renal , Diálise Peritoneal/efeitos adversos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Peritônio
4.
Curr Treat Options Oncol ; 23(9): 1303-1319, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35976553

RESUMO

OPINION STATEMENT: Gastrointestinal stromal tumor (GIST), though rare, is the most common mesenchymal tumors of the gastrointestinal tract. KIT or PDGFRα mutation plays as an oncogenic driver in the majority of GISTs. Surgical resection is the only curative treatment for localized disease. The discovery of imatinib with promising anti-tumor effect and successive tyrosine kinase inhibitors (TKI), including second-line sunitinib and third-line regorafenib, revolutionized the management of advanced and metastatic GIST over the past two decades. Recently, ripretinib and avapritinib were approved for the fourth line setting and for PDGFRA exon 18-mutant GIST in first-line setting, respectively. Despite multi-line TKIs exerted ability of disease control, drug resistance remained an obstacle for preventing rapid disease progression. Experimental TKIs or novel therapeutic targets may further improve treatment efficacy. Immune checkpoint inhibitors such as anti-programmed cell death protein-1 (PD1) and anti-CTL-associated antigen 4 (CTLA-4) showed moderate response in early phase trials composed of heavily pretreated patients. KIT/PDGFRα wild-type GISTs are generally less sensitive to imatinib and late-line TKIs. Recent studies demonstrated that targeting fibroblast growth factor receptor signaling may be a potential target for the wild-type GISTs.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/uso terapêutico , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Sunitinibe/uso terapêutico
5.
Cancer Sci ; 112(2): 803-814, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33306266

RESUMO

Polo-like kinases (PLKs) are potent regulators of cell proliferation and cell survival. Polo-like kinases are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly disease. The therapeutic effects of volasertib, a PLK inhibitor, was evaluated for the treatment of ATC either alone or in combination with sorafenib. Volasertib decreased cell viability in three ATC cell lines (8505C, 8305C, and KAT18) in a dose-dependent manner. Volasertib caused ATC cells to accumulate in G2 /M phase, activated caspase-3 activity, and induced apoptosis. Combination therapy using volasertib and sorafenib in ATC cells showed mostly synergistic effects. In vivo studies revealed that combination therapy of volasertib and sorafenib was effective in the treatment of 8505C xenografts. Single-agent volasertib treatment was sufficient to retard 8305C tumor growth. No substantial morbidity was observed in animals that received either single-agent or combination treatment. These preclinical findings suggest that volasertib could be an effective drug in treating ATC.


Assuntos
Antineoplásicos/farmacologia , Pteridinas/farmacologia , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Biomed Sci ; 28(1): 29, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888099

RESUMO

BACKGROUND: Due to the difficulties in early diagnosing and treating hepatocellular carcinoma (HCC), prognoses for patients remained poor in the past decade. In this study, we established a screening model to discover novel prognostic biomarkers in HCC patients. METHODS: Candidate biomarkers were screened by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analyses of five HCC normal (N)/tumor (T) paired tissues and preliminarily verified them through several in silico database analyses. Expression levels and functional roles of candidate biomarkers were respectively evaluated by immunohistochemical staining in N/T paired tissue (n = 120) and MTS, colony formation, and transwell migration/invasion assays in HCC cell lines. Associations of clinicopathological features and prognoses with candidate biomarkers in HCC patients were analyzed from GEO and TCGA datasets and our recruited cohort. RESULTS: We found that the transmembrane P24 trafficking protein 9 (TMED9) protein was elevated in HCC tissues according to a global proteomic analysis. Higher messenger (m)RNA and protein levels of TMED9 were observed in HCC tissues compared to normal liver tissues or pre-neoplastic lesions. The TMED9 mRNA expression level was significantly associated with an advanced stage and a poor prognosis of overall survival (OS, p = 0.00084) in HCC patients. Moreover, the TMED9 protein expression level was positively correlated with vascular invasion (p = 0.026), OS (p = 0.044), and disease-free survival (p = 0.015) in our recruited Taiwanese cohort. In vitro, manipulation of TMED9 expression in HCC cells significantly affected cell migratory, invasive, proliferative, and colony-forming abilities. CONCLUSIONS: Ours is the first work to identify an oncogenic role of TMED9 in HCC cells and may provide insights into the application of TMED9 as a novel predictor of clinical outcomes and a potential therapeutic target in patients with HCC.


Assuntos
Carcinoma Hepatocelular/fisiopatologia , Expressão Gênica , Neoplasias Hepáticas/fisiopatologia , RNA Mensageiro/metabolismo , Proteínas de Transporte Vesicular/análise , Idoso , Carcinoma Hepatocelular/diagnóstico , Cromatografia Líquida , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteômica , Espectrometria de Massas em Tandem
7.
BMC Surg ; 21(1): 37, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441134

RESUMO

BACKGROUND: Laparoscopic procedure has inherent merits of smaller incisions, better cosmesis, less postoperative pain, and earlier recovery. In the current study, we presented our method of purely laparoscopic feeding jejunostomy and compared its results with that of conventional open approach. METHODS: We retrospectively reviewed our patients from 2012 to 2019 who had received either laparoscopic jejunostomy (LJ, n = 29) or open ones (OJ, n = 94) in Chang Gung Memorial Hospital, Linkou. Peri-operative data and postoperative outcomes were analyzed. RESULTS: In the current study, we employed 3-0 Vicryl, instead of V-loc barbed sutures, for laparoscopic jejunostomy. The mean operative duration of LJ group was about 30 min longer than the OJ group (159 ± 57.2 mins vs 128 ± 34.6 mins; P = 0.001). There were no intraoperative complications reported in both groups. The patients in the LJ group suffered significantly less postoperative pain than in the OJ group (mean NRS 2.03 ± 0.9 vs. 2.79 ± 1.2; P = 0.002). The majority of patients in both groups received early enteral nutrition (< 48 h) after the operation (86.2% vs. 74.5%; P = 0.143). CONCLUSIONS: Our study demonstrated that purely laparoscopic feeding jejunostomy is a safe and feasible procedure with less postoperative pain and excellent postoperative outcome. It also provides surgeons opportunities to enhance intracorporeal suture techniques.


Assuntos
Nutrição Enteral/métodos , Jejunostomia/métodos , Laparoscopia , Feminino , Humanos , Jejunostomia/efeitos adversos , Jejunostomia/instrumentação , Laparoscopia/efeitos adversos , Masculino , Estudos Retrospectivos , Suturas , Técnicas de Fechamento de Ferimentos
8.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638938

RESUMO

Metabolic adaptation to increased oxidative phosphorylation (OXPHOS) has been found in gastrointestinal stromal tumor (GIST) upon imatinib treatment. However, the underlying mechanism of imatinib-induced OXPHOS is unknown. Discovering molecules that mediate imatinib-induced OXPHOS may lead to the development of therapeutic strategies synergizing the efficacy of imatinib. In this study, we explored the role of microRNAs in regulating OXPHOS in GIST upon imatinib treatment. Using a microarray approach, we found that miR-483-3p was one of the most downregulated miRNAs in imatinib-treated tumors compared to untreated tumors. Using an extended series of GIST samples, we further validated the downregulation of miR-483-3p in imatinib-treated GIST samples by RT-qPCR. Using both gain- and loss-of-function experiments, we showed that miR-483-3p could regulate mitochondrial respiratory Complex II expression, suggesting its role in OXPHOS regulation. Functionally, miR-483-3p overexpression could rescue imatinib-induced cell death. These findings provide the molecular link for imatinib-induced OXPHOS expression and the biological role of miR-483-3p in regulating cell viability upon imatinib treatment.


Assuntos
Antineoplásicos/farmacologia , Complexo II de Transporte de Elétrons/metabolismo , Neoplasias Gastrointestinais/metabolismo , Tumores do Estroma Gastrointestinal/metabolismo , Mesilato de Imatinib/farmacologia , MicroRNAs/metabolismo , Mitocôndrias/enzimologia , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mesilato de Imatinib/uso terapêutico , MicroRNAs/genética , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , RNA Mensageiro/genética , Transdução de Sinais/genética , Transfecção
9.
Oncologist ; 25(7): e1021-e1030, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32058649

RESUMO

PURPOSE: The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for fluorouracil-based adjuvant chemotherapy in colorectal cancer has been a paradigm shift. However, whether this applies to gastric cancer is questionable. Furthermore, we herein investigated whether and how autophagy plays a role in MSI-relevant chemoresistance. MATERIALS AND METHODS: A total of 929 patients with deficient MMR (dMMR) and proficient MMR (pMMR) gastric cancers who underwent curative-intent gastrectomy were enrolled. We compared clinicopathological variables and survival among dMMR and pMMR cohorts and tested the responses of MSI-high and microsatellite stable (MSS) gastric cancer cell lines to 5-fluorouracil (5-FU) with or without chloroquine, an autophagy inhibitor. RESULTS: We identified an 8.9% prevalence of dMMR cases (83 out of 929) in our cohort. This was associated with old age, tumor site at the distal stomach, an intestinal phenotype, fewer nodal metastasis, and early pathological stages. MMR was an independent prognostic factor after multivariate adjustment. Overall survival (OS) of dMMR patients was better than that of the pMMR patients but was only applicable to stage III patients. There was no difference in OS between dMMR patients treated with or without adjuvant chemotherapy, although the latter showed more medical morbidities. The MSI-high gastric cancer cell lines, versus the MSS counterparts, displayed increased resistance to 5-FU and increased autophagy. Interestingly, autophagy inhibition abrogated the chemoresistance. CONCLUSION: Our data show that fluorouracil-based adjuvant chemotherapy does not work for dMMR cases, if not worse. Autophagy inhibition and/or immune checkpoint inhibition might be promising alternative strategies for gastric cancer treatment. IMPLICATIONS FOR PRACTICE: The use of microsatellite instability (MSI) and mismatch repair (MMR) as predictive biomarkers for adjuvant chemotherapy in colorectal cancer has caused a paradigm shift in cancer therapy, although its implications in gastric cancer are still questionable. The data obtained in the current study indicate that MSI-MMR is an independent prognostic factor for gastric cancer. Standard fluorouracil-based adjuvant chemotherapy did not work for deficient MMR cases, and was likely worse. Instead, strategies like autophagy inhibition and/or immune checkpoint inhibition should be taken into consideration in the future.


Assuntos
Neoplasias Colorretais , Neoplasias Gástricas , Autofagia , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Humanos , Instabilidade de Microssatélites , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
10.
BMC Cancer ; 20(1): 422, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410631

RESUMO

BACKGROUND: Chemotherapy with gemcitabine and cisplatin has been the standard of care in first-line chemotherapy for advanced biliary tract cancer (BTC) since the trial ABC-02 was published in 2010. We aimed to investigate the prognostic and predictive factors of this regimen in a cohort of Taiwanese patients with advanced BTC. METHODS: A total of 118 patients with histologically confirmed BTC treated at Chang Gung Memorial Hospital at Linkou from 2012 to 2017 were retrospectively reviewed. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.6 months and 8.4 months, respectively. In the multivariate analysis, neutrophil to lymphocyte ratio (NLR) > 7.45, biliary drainage requiring both percutaneous transhepatic cholangiography drainage (PTCD) and internal stenting, and tumor responses with progressive diseases and not assessed were independent poor prognostic factors for PFS. Male sex, NLR > 7.45, alkaline phosphatase> 94 U/L, biliary drainage requiring both PTCD and internal stenting, and tumor responses with stable disease, progressive diseases and not assessed were independent poor prognostic factors for OS. Monocyte to lymphocyte ratio (MLR) ≤ 0.28 was the only significant predictive factor for the tumor response. Patients with complete response/partial response had significantly lower MLR than patients with other tumor responses. CONCLUSION: We identified three important prognostic factors, namely tumor response, NLR, and biliary drainage requiring both PTCD and internal stenting for both PFS and OS. MLR was the only significant predictive factor for the tumor response. These findings could provide physicians with more information to justify the clinical outcomes in patients with advanced BTC in real-world practice.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Idoso , Neoplasias do Sistema Biliar/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan , Gencitabina
11.
BMC Surg ; 20(1): 179, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762661

RESUMO

BACKGROUND: Submucosal tumors (SMTs) of different etiologies exist from esophagus to rectum. Esophagogastric junction (EGJ) is one of the known difficult locations for tumor resection. Although minimally invasive surgery (MIS) is a well-established approach for gastrointestinal surgery, there is no consensus that MIS for resection of SMTs around EGJ is superior to laparotomy. We tried to clarify the factors that determine the surgeons' choices between these two approaches. METHODS: From January 2002 to June 2016, 909 patients with SMTs underwent resection in our department. Among them, 119 patients (13%) had SMTs around EGJ were enrolled by retrospective review. The clinicopathological features and tumor-related parameters were reviewed and analyzed. RESULTS: The cohort was stratified into three groups according to the extent of gastrectomy and surgical approaches. The three groups are as following: major gastrectomy (n = 13), minor gastrectomy by laparotomy (n = 51), and minor gastrectomy with MIS (n = 55). The average tumor size was significantly larger in the major gastrectomy group than in the two minor gastrectomy groups; however, there was no difference between the two minor gastrectomy groups (5.33 cm, 4.07 cm, and 3.69 cm, respectively). The minor gastrectomy with MIS required least hospital stay and operation duration also. We re-stratify the two minor gastrectomy groups (n = 106) according to the orientation of SMTs around the EGJ into 4 zones. Most of SMTs located on the greater curvature side of the EGJ were resected with MIS (82% versus 18%), whereas SMTs in the other zones were resected more often by laparotomy (59% versus 41%). There was no surgical mortality within the cohort, while minor gastrectomy with MIS yielded least number of leakages among the three groups. CONCLUSIONS: For SMTs around the EGJ, larger tumors (diameter of more than 5 cm) are more likely to be resected with major gastrectomy. To resect SMTs around the EGJ in a wedge-like (minor gastrectomy) fashion, tumors located other than the greater curvature side were more often resected by laparotomy. However, MIS yielded acceptable safety and surgical outcomes compared to conventional laparotomy for SMTs around the EGJ of the same size.


Assuntos
Gastrectomia , Laparoscopia , Neoplasias Gástricas , Adulto , Idoso , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
12.
Mol Carcinog ; 58(2): 270-278, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30334579

RESUMO

Cholangiocarcinoma (CCA) is a devastating disease with very poor prognosis due to late diagnosis and resistance to traditional chemotherapies and radiotherapies. Herein, thioacetamide (TAA)-induced rat CCA model and CGCCA cell line were used; we aim to study the cytogenetic features during tumoral development of CCA and uncover the mystery regarding carcinogenesis of CCA. The Array comparative genomic hybridization analysis, in silico method, gene knockdown, Western blot, cell count proliferation assay, clonogenecity assay, and IHC staining were applied in this study. Array comparative genomic hybridization analysis was performed on all different TAA-induced phases of rat tissues to reveal the certain pattern, +2q45, +Xq22, -12p12, have been identified for the tumor early stage, where involve the gene TNNI3K. In addition, 16 genes and 3 loci were associated with rapid tumor progression; JAK-STAT signaling pathway was highly correlated to late stage of CCA. In silico database was used to observe TNNI3K was highly express at tumor part compared with normal adjacent tissue in CCA patients from TCGA dataset. Furthermore, the growth of TNNI3K-knockdown SNU308 and HuCCT1 cells decreased when compared with cells transfected with an empty vector cell demonstrated by proliferation and colonogenecity assay. Besides, over expression of TNNI3K was especially confirmed on human CCA tumors and compared with the intrahepatic duct stone bile duct tissues and normal bile duct tissues (P < 0.001). Our findings might uncover the mystery regarding carcinogenesis of CCA, and provide the potential genetic mechanism to the clinicians some ideas for the patients' treatment.


Assuntos
Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Tioacetamida/efeitos adversos , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/induzido quimicamente , Neoplasias dos Ductos Biliares/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Colangiocarcinoma/induzido quimicamente , Colangiocarcinoma/metabolismo , Hibridização Genômica Comparativa , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Serina-Treonina Quinases , Ratos , Transdução de Sinais , Adulto Jovem
15.
Int J Mol Sci ; 20(3)2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30682771

RESUMO

Patients with advanced biliary tract cancers (BTCs), including cholangiocarcinoma (CCA), have poor prognosis so novel treatment is warranted for advanced BTC. In current review, we discuss the limitations of current treatment in BTC, the importance of mTOR signalling in BTC, and the possible role of mTOR inhibitors as a future treatment in BTC. Chemotherapy with gemcitabine-based chemotherapy is still the standard of care and no targeted therapy has been established in advanced BTC. PI3K/AKT/mTOR signaling pathway linking to several other pathways and networks regulates cancer proliferation and progression. Emerging evidences reveal mTOR activation is associated with tumorigenesis and drug-resistance in BTC. Rapalogs, such as sirolimus and everolimus, partially inhibit mTOR complex 1 (mTORC1) and exhibit anti-cancer activity in vitro and in vivo in BTC. Rapalogs in clinical trials demonstrate some activity in patients with advanced BTC. New-generation mTOR inhibitors against ATP-binding pocket inhibit both TORC1 and TORC2 and demonstrate more potent anti-tumor effects in vitro and in vivo, however, prospective clinical trials are warranted to prove its efficacy in patients with advanced BTC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/metabolismo , Colangiocarcinoma/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Animais , Neoplasias do Sistema Biliar/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Humanos , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores
17.
BMC Gastroenterol ; 18(1): 180, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514231

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection. METHODS: A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed. RESULTS: Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients. CONCLUSION: Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos
18.
Surg Endosc ; 32(4): 1793-1801, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28916962

RESUMO

BACKGROUND: The aim of this study was to evaluate the benefits of cholecystectomy on mitigating recurrent biliary complications following endoscopic treatment of common bile duct stone. METHODS: We used the data from the Taiwan National Health Insurance Research Database to conduct a population-based cohort study. Among 925 patients who received endoscopic treatment for choledocholithiasis at the first admission from 2005 to 2012, 422 received subsequent cholecystectomy and 503 had gallbladder (GB) left in situ. After propensity score matching with 1:1 ratio, the cumulative incidence of recurrent biliary complication and overall survival was analyzed with Cox's proportional hazards model. The primary endpoint of this study is recurrent biliary complications, which require intervention. RESULTS: After matching, 378 pairs of patients were identified with a median follow-up time of 53 (1-108) months. The recurrent rate of biliary complications was 8.20% in the cholecystectomy group and 24.87% in the GB in situ group (p < 0.001). In the multivariate Cox regression analysis, the only independent risk factor for recurrent biliary complications was GB left in situ (hazard ratio [HR] 3.55, 95% CI 2.36-5.33). CONCLUSIONS: Cholecystectomy after endoscopic treatment of common bile duct stone reduced the prevalence of recurrent biliary complications.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Colecistectomia , Coledocolitíase/cirurgia , Idoso , Idoso de 80 Anos ou mais , Coledocolitíase/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
Surg Endosc ; 32(3): 1506-1514, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28916859

RESUMO

BACKGROUND: Near-infrared (NIR) fluorescence cholangiography by systemic administration of indocyanine green (ICG) enhances the visualization of the biliary tree anatomy. However, the simultaneous enhancement of liver parenchyma can disturb the visualization of critical details. We herein proposed a new technique of NIR cholecystocholangiography by intragallbladder ICG injection to increase the safety during laparoscopic cholecystectomy. METHODS: A total of 46 patients scheduled for laparoscopic cholecystectomy for symptomatic lithiasis (n = 21) or cholecystitis (n = 25) were enrolled. A fluorescence cholangiography by direct gallbladder injection of ICG was performed in all cases. Of them, the ICG was injected through a previously placed percutaneous transhepatic gallbladder drainage catheter (n = 18) or by intraoperative, percutaneous needle puncture of the gallbladder (n = 28). Visualization of biliary structures, including the cystic duct (CD), the common bile and hepatic ducts (CBD and CHD), the gallbladder neck, and the Hartmann's pouch (HP), was performed using White Light (served as control modality) and by NIR enhancement. RESULTS: Cholecystocholangiography provided a significantly higher rate of visualization of the CD in case of cholecystitis with mild adhesions, and an improved visualization of the HP, CBD, and CHD in case of severe inflammation, when compared to White Light observation. There were no benefits of NIR in case of non-inflamed lithiasis. CONCLUSIONS: Clinical translation of NIR cholecystocholangiography has been successful with a noise-free visualization of biliary anatomy. It can be considered in difficult cases to increase the safety of laparoscopic cholecystectomy.


Assuntos
Sistema Biliar/diagnóstico por imagem , Colangiografia/métodos , Colecistectomia Laparoscópica/métodos , Colecistografia/métodos , Corantes/administração & dosagem , Verde de Indocianina/administração & dosagem , Adulto , Colecistite/cirurgia , Colelitíase/cirurgia , Ducto Colédoco/diagnóstico por imagem , Ducto Cístico/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Vesícula Biliar/diagnóstico por imagem , Ducto Hepático Comum/diagnóstico por imagem , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Imagem Óptica/métodos , Estudos Prospectivos
20.
J Formos Med Assoc ; 117(6): 480-487, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28735662

RESUMO

BACKGROUND/PURPOSE: To investigate the diagnostic accuracy of 68Ga-DOTATOC and 18F-FDG PET/CT to identify the primary foci in Taiwanese patients with clinically suspected neuroendocrine tumors (NET) and NET of unknown primary site. METHODS: Patients with clinically suspected NET and NET of unknown primary site were eligible. All participants underwent a conventional workup (including CT, MR, endoscopic ultrasound), 68Ga-DOTATOC, and 18F-FDG PET/CT. The results of pathology and findings on clinical follow-up served as the gold standard. RESULTS: Among the 36 patients included in the study, we were able to identify the primary tumor in 17 participants (47.2%). The overall sensitivity values of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 88%, 41%, and 53%, respectively, whereas the specificities were 100%, 100%, 68%, respectively. The areas under curve of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 0.941, 0.706, and 0.607, respectively. 68Ga-DOTATOC was more sensitive than 18F-FDG and more specific than conventional workup. Treatment changes as a result of 68Ga-DOTATOC PET/CT findings occurred in 12 (33.3%) of the 36 study participants. CONCLUSION: Our data confirm the usefulness of 68Ga-DOTATOC in the identification of NET. In addition, treatment modifications as a result of 68Ga-DOTATOC PET/CT findings were evident in approximately one third of NET patients.


Assuntos
Fluordesoxiglucose F18 , Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/análogos & derivados , Compostos Organometálicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Taiwan , Adulto Jovem
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