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1.
Surg Endosc ; 36(10): 7811-7817, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35648212

RESUMO

BACKGROUND: Colorectal ESD is difficult because of the poor maneuverability and difficulty of mucosal flap creation. Diving, Lifting and Horizontal (DLH) dissection technique and loop-clip traction are two different methods to facilitate mucosal trimming and adequate mucosal flap creation. We combined the advantages of these two techniques (DLH+T) in our daily practice colorectal ESD since July 2020. OBJECTIVE: The purpose of this study was to examine the outcomes of DLH+T dissection compared with the conventional dissection. METHODS: We retrospectively reviewed the clinical using DLH+T dissection compared with the conventional dissection since January 2018 at a single tertiary care institution. Postoperative short-term outcomes were investigated after the procedure including mucosal flap creation time, dissection time, dissection speed, en bloc resection rate, and perioperative complications. RESULTS: 28 lesions were in DLH+T dissection group and 39 lesions in the conventional dissection group. The outcomes including en bloc resection rate, dissection speed, and complication between the two groups were similar. The mean mucosal flap creation time (p = 0.035) and the mean dissection speed (p = 0.041) of the DLH+T dissection group was significantly shorter and faster. CONCLUSION: DLH dissection followed by loop-clip traction (DLH+T) technique is a useful technique for safe, efficient, and adequate mucosal flap creation, which can increase the dissection speed and may prevent complication, especially in biopsy-related submucosal fibrosis.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Humanos , Remoção , Estudos Retrospectivos , Instrumentos Cirúrgicos , Tração/métodos , Resultado do Tratamento
2.
J Oncol Pharm Pract ; 28(6): 1293-1302, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34060351

RESUMO

INTRODUCTION: In Taiwan, given the discrepancy between current treatment guidelines and reimbursement options, patients might require a tool to support their decision-making process when selecting a regimen for metastatic colorectal cancer, especially therapeutic strategies, and subsequent costs, along with efficacy and safety outcomes. Therefore, we developed a patient decision aid (PDA) to support patients in choosing between treatment options recommended based on the current evidence and those reimbursed by the Taiwanese National Health Insurance. METHODS: By carefully reviewing the updated data and then interpreting the clinical tool, we conducted a needs assessment using a serial questionnaire to test for a step-by-step adjustment of the PDA. RESULTS: Patients, their relatives, and medical team members were most concerned about outcomes, such as overall survival, progression-free survival, objective response rate, tumor shrinkage to resectable status, total medical cost, severe gastrointestinal perforation, and severe skin reaction. After a serial alpha test for quality, we performed quantitative evaluation and beta tests, revealing average scores of more than 4 points (on a scale of 1-5) for both perceptibility and utility. CONCLUSIONS: The present findings suggest that PDAs are useful and supplement the shared decision-making practice, helping patients make decisions about preferences and consider the pros and cons of treatment regimens, along with insurance reimbursement options.


Assuntos
Participação do Paciente , Neoplasias Retais , Técnicas de Apoio para a Decisão , Humanos , Inquéritos e Questionários , Taiwan
3.
Dis Colon Rectum ; 64(2): 241-247, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394769

RESUMO

BACKGROUND: Colorectal endoscopic submucosal dissection is typically performed by specialized knife, such as a dual knife. However, it is not covered by Taiwan's National Health Insurance. In the literature review, using a traditional snare tip for endoscopic submucosal dissection has been reported for stomach lesions only. OBJECTIVE: The purpose of this study was to evaluate the outcomes of colorectal endoscopic submucosal dissection using a snare tip. DESIGN: We retrospectively reviewed the clinical using of a snare tip compared with a dual knife for colorectal endoscopic submucosal dissection. Postoperative short- and long-term outcomes were investigated after the procedure. SETTINGS: This study was conducted at a single tertiary care institution. PATIENTS: Patients who could not afford the expense of a specialized knife were included. MAIN OUTCOME MEASURES: Dissection time, dissection speed, and perioperative complications were used for short-term outcome measurement. Recurrence-free rate was used for long-term outcome measurement. RESULTS: Twenty-one lesions were in the snare tip group and 57 lesions in the dual knife group. The outcomes, including rate of en bloc resection, complication, local recurrence, and recurrence-free interval, between the 2 groups were similar. The mean resected specimen diameter in the dual knife group is larger than the snare tip group (p = 0.041). The dissection time of the snare tip group was shorter than the dual knife group (p = 0.025). However, the dissection speed was significantly slower in the snare tip group than in the dual knife group (p = 0.008). LIMITATIONS: This study was a retrospective and single doctor chart review in nature with a limited patient number. CONCLUSIONS: The snare tip is an alternative tool for colorectal endoscopic submucosal dissection in a selected population without the support of specialized knives, such as the dual knife. Although the dissection speed is slower using a snare tip, it is still a recommended technique for developing country or low-income patients.


Assuntos
Adenocarcinoma/cirurgia , Adenoma/cirurgia , Pólipos do Colo/cirurgia , Colonoscopia/instrumentação , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/instrumentação , Adenocarcinoma/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Adulto , Idoso , Pólipos do Colo/diagnóstico por imagem , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico por imagem , Intervalo Livre de Doença , Ressecção Endoscópica de Mucosa/métodos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
J Clin Pharm Ther ; 46(2): 424-432, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33135261

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The role of continuous/extended beta-lactam infusions (CEIs) in improving clinical outcomes among critically ill patients remains controversial. Therefore, we aimed to compare the clinical efficacy of CEI versus intermittent administration (IA) of beta-lactams by performing a systematic review and meta-analysis. METHODS: PubMed, the Cochrane Library and Embase were searched from inception until December 2018 for studies comparing clinical outcomes of CEI versus IA in critically ill patients. The meta-analysis included 18 randomized controlled trials (RCTs) and 13 non-RCTs. RESULTS AND DISCUSSION: For CEI versus IA, the summary relative risk (RR) for overall mortality and clinical cure was 0.82 (95% confidence interval [CI]: 0.72-0.94) and 1.31 (95% CI: 1.15-1.49), respectively. Subgroup and meta-regression analyses of the loading dose revealed a significantly increased clinical cure rate in the loading-dose group (RR: 1.44, 95% CI: 1.22-1.69), which remained significant after adjustments for beta-lactam type, and association between clinical cure and loading dose for clinical cure (RR: 1.47, 95% CI: 1.20-1.80; p = .001). Subgroup analysis of administration type indicated that both groups had low mortality and high clinical cure rates; however, the heterogeneity analysis did not support an association across continuous infusion and extended infusion groups. Subgroup analysis of the Acute Physiology and Chronic Health Evaluation (APACHE) score was conducted; according to APACHE scores ≥ 16, overall mortality and clinical cure significantly differed between CEI and IA. WHAT IS NEW AND CONCLUSION: CEIs with loading-dose treatment may significantly improve the clinical outcomes in critically ill sepsis or septic shock patients.


Assuntos
Estado Terminal/terapia , beta-Lactamas/administração & dosagem , APACHE , Esquema de Medicação , Mortalidade Hospitalar , Humanos , Infusões Intravenosas , Tempo de Internação , Testes de Sensibilidade Microbiana , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , beta-Lactamas/uso terapêutico
5.
Surg Endosc ; 34(2): 1006-1011, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31482351

RESUMO

BACKGROUND: Conventional lesion-up colorectal ESD has the potential risk of iatrogenic perforation due to the knife's direction toward the muscular layer of the bowel wall. If we rotate the endoscope to the proper position, the mucosal flap is easy to be lifted down by tip attachment and the knife is easy to approach the proper dissection plane, which may prevent the perforation and facilitate difficult ESD. METHODS: We aimed to retrospectively assess the safety and efficacy of this rotating technique compared with the conventional lesion-up dissection regardless of shape, location, or size of the tumor, and investigated in short- and long-term outcomes following the ESD procedure. RESULTS: 41 lesions were enrolled into rotating technique group and 37 lesions in lesion-up group. The dissection speed was significantly faster in the rotating technique group (p = 0.023). R0 resection rate was significantly higher in rotating technique group (p = 0.008). The rate of perioperative complication was significantly higher in lesion-up method group (p = 0.003). Local recurrence was higher in lesion-up group (p = 0.001). Recurrence-free rate was higher in rotating technique group (p = 0.018). CONCLUSION: The endoscope rotating is a useful technique for difficult colorectal ESD due to easy approaching the proper dissection plane. This technique also increases the rate of en bloc resections, R0 resections regardless of size, shape, and location and improves dissection speed without increasing the incidence of adverse events.


Assuntos
Adenocarcinoma/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscópios , Colonoscopia/instrumentação , Dissecação/instrumentação , Dissecação/métodos , Ressecção Endoscópica de Mucosa/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Resultado do Tratamento
6.
Nucleic Acids Res ; 46(3): 1157-1166, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29177422

RESUMO

Rpc82 is a TFIIE-related subunit of the eukaryotic RNA polymerase III (pol III) complex. Rpc82 contains four winged-helix (WH) domains and a C-terminal coiled-coil domain. Structural resolution of the pol III complex indicated that Rpc82 anchors on the clamp domain of the pol III cleft to interact with the duplex DNA downstream of the transcription bubble. However, whether Rpc82 interacts with a transcription factor is still not known. Here, we report that a structurally disordered insertion in the third WH domain of Rpc82 is important for cell growth and in vitro transcription activity. Site-specific photo-crosslinking analysis indicated that the WH3 insertion interacts with the TFIIB-related transcription factor Brf1 within the pre-initiation complex (PIC). Moreover, crosslinking and hydroxyl radical probing analyses revealed Rpc82 interactions with the upstream DNA and the protrusion and wall domains of the pol III cleft. Our genetic and biochemical analyses thus provide new molecular insights into the function of Rpc82 in pol III transcription.


Assuntos
DNA Fúngico/química , DNA/química , Regulação Fúngica da Expressão Gênica , RNA Polimerase III/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Fator de Transcrição TFIIIB/química , Iniciação da Transcrição Genética , Sequência de Aminoácidos , Sequência de Bases , Benzofenonas/química , Sítios de Ligação , Clonagem Molecular , Reagentes de Ligações Cruzadas/química , DNA/genética , DNA/metabolismo , DNA Fúngico/genética , DNA Fúngico/metabolismo , Radical Hidroxila/química , Modelos Moleculares , Fenilalanina/análogos & derivados , Fenilalanina/química , Plasmídeos/química , Plasmídeos/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , RNA Polimerase III/genética , RNA Polimerase III/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Fator de Transcrição TFIIIB/genética , Fator de Transcrição TFIIIB/metabolismo
7.
Int J Colorectal Dis ; 34(3): 513-518, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30617410

RESUMO

PURPOSE: A temporary loop stoma is often created after laparoscopic colorectal cancer surgery. Peristomal adhesions may make stoma closure into a complicated operation. We demonstrated how to place the SurgiWrap® adhesion barrier film and evaluated the peristomal adhesion severity and feasibility of stoma closure. METHODS: This is a retrospective case-control study. Patients were divided into a study group (placement of adhesion barrier film) and a control group (no placement). Patient characteristics, operative data, and severity of adhesions were recorded. We used logistic regression to probe the association between the variables and the adhesion severity. RESULTS: A total of 180 patients were identified with 60 in the study group and 120 in the control group. In the study group, the adhesion severity (p < 0.001), operative time (p = 0.025), and time to flatus (p = 0.042) are significantly reduced. In logistic regression analysis, placement of the film (p < 0.001), neoadjuvant concurrent chemoradiotherapy (p = 0.041), and time interval between stoma creation and closure ≧ 12 weeks (p = 0.038) are three significant factors influencing the peristomal adhesion. CONCLUSION: The placement of SurgiWrap® adhesion barrier film around the loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the stoma closure in terms of operative time and time to flatus.


Assuntos
Neoplasias Colorretais/cirurgia , Cirurgia Colorretal , Laparoscopia , Estomas Cirúrgicos/patologia , Aderências Teciduais/cirurgia , Adesivos Teciduais/farmacologia , Cavidade Abdominal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Eur J Clin Pharmacol ; 74(9): 1111-1119, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29845351

RESUMO

BACKGROUND: Until recently, the role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation during immunosuppressive therapy or chemotherapy in patients with resolved HBV infection was unclear. The aim of the study reported here was to compare the efficacy of antiviral prophylaxis versus that of non-prophylaxis in resolved HBV-infected patients undergoing chemotherapy or immunosuppressive therapy. METHODS: PubMed, the Cochrane library, and the ClinicalTrials.gov website were searched from inception until December 2017. Studies comparing reactivation in prophylaxis versus non-prophylaxis in patients undergoing immunosuppressive therapy or chemotherapy were included. The meta-analysis was performed to calculate the relative risk (RR) and the pooled estimates. RESULTS: A meta-analysis was conducted of 13 studies (2 randomized controlled trials [RCTs] and 11 cohort studies). The summary RR for HBV reactivation was 0.47 (95% confidence interval [CI] 0.13-1.69) for antiviral prophylaxis versus non-prophylaxis. Both of the RCTs included in the meta-analysis enrolled patients treated with rituximab. Subgroup analyses showed that the two RCTs ± high-quality cohort studies showed a decreased risk of HBV reactivation among the antiviral prophylaxis groups (RCT 1: RR 0.13, 95% CI 0.02-0.70; P = 0.02; RCT 2: 0.28, 95% CI 0.08-0.98; P = 0.05). Subgroup analyses further showed that the cohort studies did not support an association between the antiviral prophylaxis groups and HBV reactivation (RR 0.62, 95% CI 0.14-2.83; P = 0.54); adjusting for confounding factors, such as detectable anti-HBs antibodies, failed to produce a significant association (RR,0.29, 95% CI 0.07-1.28; P = 0.10). CONCLUSION: Our meta-analyses did not show an association between antiviral prophylaxis use and risk of HBV reactivation. As using only the RCTs ± high-quality cohort studies data rendered this association significant, clinicians can consider providing antiviral prophylaxis to patients with resolved HBV infection who are undergoing rituximab-based therapy.


Assuntos
Antineoplásicos/efeitos adversos , Antivirais/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/prevenção & controle , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Ativação Viral/efeitos dos fármacos , Antivirais/efeitos adversos , Esquema de Medicação , Hepatite B/diagnóstico , Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Fatores de Risco , Resultado do Tratamento
10.
Tumour Biol ; 37(5): 6987-96, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26662956

RESUMO

Combining antitumor agents with bioactive compounds is a potential strategy for improving the effect of chemotherapy on cancer cells. The goal of this study was to elucidate the antitumor effect of the flavonoid, fisetin, combined with the multikinase inhibitor, sorafenib, against human cervical cancer cells in vitro and in vivo. The combination of fisetin and sorafenib synergistically induced apoptosis in HeLa cells, which is accompanied by a marked increase in loss of mitochondrial membrane potential. Apoptosis induction was achieved by caspase-3 and caspase-8 activation which increased the ratio of Bax/Bcl-2 and caused the subsequent cleavage of PARP level while disrupting the mitochondrial membrane potential in HeLa cells. Decreased Bax/Bcl-2 ratio level and mitochondrial membrane potential were also observed in siDR5-treated HeLa cells. In addition, in vivo studies revealed that the combined fisetin and sorafenib treatment was clearly superior to sorafenib treatment alone using a HeLa xenograft model. Our study showed that the combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway. This combined fisetin and sorafenib treatment represents a novel therapeutic strategy for further clinical developments in advanced cervical cancer.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Flavonoides/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/agonistas , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Flavonóis , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Niacinamida/farmacologia , Sorafenibe , Carga Tumoral/efeitos dos fármacos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Proc Natl Acad Sci U S A ; 109(47): 19232-7, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23132938

RESUMO

Transcription initiation by eukaryotic RNA polymerase (Pol) III relies on the TFIIE-related subcomplex C82/34/31. Here we combine cross-linking and hydroxyl radical probing to position the C82/34/31 subcomplex around the Pol III active center cleft. The extended winged helix (WH) domains 1 and 4 of C82 localize to the polymerase domains clamp head and clamp core, respectively, and the two WH domains of C34 span the polymerase cleft from the coiled-coil region of the clamp to the protrusion. The WH domains of C82 and C34 apparently cooperate with other mobile regions flanking the cleft during promoter DNA binding, opening, and loading. Together with published data, our results complete the subunit architecture of Pol III and indicate that all TFIIE-related components of eukaryotic and archaeal transcription systems adopt an evolutionarily conserved location in the upper part of the cleft that supports their functions in open promoter complex formation and stabilization.


Assuntos
Conformação de Ácido Nucleico , Regiões Promotoras Genéticas/genética , Subunidades Proteicas/química , RNA Polimerase III/química , Saccharomyces cerevisiae/enzimologia , Domínio Catalítico , Reagentes de Ligações Cruzadas/farmacologia , Luz , Lisina/metabolismo , Modelos Moleculares , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/efeitos da radiação , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos da radiação , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas/metabolismo , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/efeitos da radiação , RNA Polimerase III/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/efeitos da radiação , Relação Estrutura-Atividade
14.
Artigo em Inglês | MEDLINE | ID: mdl-38879376

RESUMO

INTRODUCTION: Bevacizumab and antiepidermal growth factor receptor-blocking (anti-EGFR) agents plus chemotherapy are first-line therapies for metastatic colorectal cancer (mCRC). Conversion surgery may improve outcomes; however, the extent to which it explains the difference in mortality rates among treatments is unclear. Herein, we aimed to assess the effects of conversion surgery on survival outcomes of patients with unresectable mCRC treated with bevacizumab and anti-EGFR agents. MATERIALS AND METHODS: This retrospective cohort study included patients with mCRC treated with bevacizumab and anti-EGFR agents as first-line therapy. We estimated the direct and indirect effects of treatments by comparing the mortality risk associated with targeted therapy type. Hazard ratios (HR) and the corresponding confidence intervals (CI) were estimated. Mediation analysis was used to estimate hazard ratio differences, and the proportion mediated. RESULTS: A total of 5,106 patients were included. The natural indirect effect of conversion surgery reduced mortality risk (HR: 0.95; 95% CI, 0.93-0.97), with a mediated proportion of 42% after propensity score adjustment. In subgroup analyses, KRAS wild-type (HR: 0.94; 95% CI: 0.91-0.97), left tumor sidedness (HR: 0.94; 95% CI, 0.91-0.96), and liver resection (HR: 0.95; 95% CI, 0.93-0.98) were associated with reduced risks of mortality. The controlled and total direct effects of targeted therapy were associated with reduced mortality risk in the anti-EGFR-treated group compared to those in the bevacizumab-treated group; however, this effect was not statistically significant. CONCLUSION: Conversion surgery may account for the difference in survival outcomes between users of the anti-EGFR agents and bevacizumab.

15.
Ther Adv Med Oncol ; 16: 17588359241246427, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655393

RESUMO

Background: Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC). Objective: To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs). Design: Retrospective cohort study. Methods: Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs. Results: We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively. Conclusion: Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.

16.
Anticancer Res ; 44(4): 1619-1628, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537994

RESUMO

BACKGROUND/AIM: Postoperative survival outcomes are crucial in treatment decision making. This study aimed to compare the efficacy of adjuvant chemotherapy (AC)-alone with that of chemotherapy + targeted agents (CTA) in patients with metastatic colorectal cancer (mCRC) and to investigate the association between neoadjuvant therapy and survival. PATIENTS AND METHODS: Patients who underwent primary tumor excision and metastasectomy were identified in the Taiwan Cancer Registry from 2010 to 2019. The analysis assessed the influence of adjuvant therapy on survival and examined the interactions between adjuvant therapy types (AC-alone and CTA) and patient characteristics with respect to overall survival. RESULTS: Overall, 1,728 and 757 patients received AC alone and CTA, respectively. Compared to AC alone, adjuvant CTA yielded similar mortality after surgery [hazard ratio (HR)=1.03; 95% confidence interval (CI)=0.91-1.17] but resulted in marginally reduced mortality among patients treated with neoadjuvant therapy with targeted agents (HR=0.6; 95%CI=0.34-1.05) after propensity score matching. In patients with mCRC, those who received targeted agents preoperatively and postoperatively in combination with AC had the highest mortality rate (HR=1.75; 95%CI=1.33-2.32). CONCLUSION: Overall survival is comparable between adjuvant CTA and AC alone, but adjuvant CTA may be more beneficial in patients with mCRC who undergo neoadjuvant therapy with targeted agents.


Assuntos
Neoplasias do Colo , Neoplasias Retais , Humanos , Terapia Combinada , Quimioterapia Adjuvante/métodos , Terapia Neoadjuvante , Estudos Retrospectivos
17.
Am J Cancer Res ; 14(5): 2172-2186, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859829

RESUMO

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

18.
Anticancer Res ; 43(11): 5127-5138, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37909992

RESUMO

BACKGROUND/AIM: The study aimed to determine the effectiveness of cetuximab and panitumumab on the survival of patients with metastatic colorectal cancer or those who had undergone conversion surgery and to identify their prognostic factors. PATIENTS AND METHODS: This retrospective cohort study used data from patients with metastatic colorectal cancer who received cetuximab or panitumumab as first-line targeted agent-based therapy. Overall survival and conversion surgery rates were evaluated, and the prognostic factors were determined. RESULTS: A total of 1,749 and 318 patients received cetuximab or panitumumab with chemotherapy, respectively. Overall survival and conversion surgery rates were similar between the cetuximab [hazard ratio (HR)=0.96] and panitumumab groups (HR=1.00). The prognostic factors associated with metastasectomy significantly lowered mortality among patients with metastatic colorectal cancer (HR=0.61). Older age (≥70 years), tumor stage 4B and 4C, right-sided tumors, mucinous adenocarcinoma, primary tumor resection, and the number of positive lymph nodes were associated with higher mortality and lower conversion surgery rates. CONCLUSION: Though panitumumab- and cetuximab-based therapies showed no differences, several factors, such as age over 70 years old, tumor stage 4B and 4C, undifferentiated carcinoma, mucinous carcinoma, right-sided tumor, number of positive lymph nodes, obstruction, and primary tumor resection increased the mortality risk of patients. This study underscores the importance of metastasectomy in current treatment guidelines and future clinical trials.


Assuntos
Neoplasias do Colo , Neoplasias Retais , Humanos , Idoso , Cetuximab/uso terapêutico , Panitumumabe/uso terapêutico , Estudos Retrospectivos
19.
Eur J Surg Oncol ; 49(2): 445-451, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36208981

RESUMO

INTRODUCTION: Treatment guidelines for colorectal cancer (CRC) indicate that surgical intervention within 4 weeks or 8 weeks after bevacizumab therapy might increase the risk of postoperative complications and mortality, especially in patients who received emergent operation. Therefore, we aimed to assess the association between different surgical timings, emergent or elective surgery, and the risk of postoperative mortality. MATERIALS AND METHODS: Using the Taiwan National Health Insurance Database and Taiwan Cancer Registry, we identified patients with metastatic colorectal cancer (mCRC) who underwent surgery within 1 year of receiving bevacizumab between January 2010 and December 2017. The primary outcomes were 30-day, 60-day, and in-hospital mortality; the secondary outcomes were hospital stay, 30-day readmission rate, and surgical complications. Multivariate analysis was used to adjust for confounders. RESULTS: This study included 2,047 patients. In the multivariate analysis, patients who underwent emergent operation and had higher Charlson scores had a significantly higher mortality rate. Patients with a longer interval to surgery, more cycles of bevacizumab treatment, and distal metastectomy had the opposite result. In subgroup analysis, patients who received emergent operation within 28 days had the highest surgical mortality. CONCLUSIONS: The interval to operation among mCRC patients who receive bevacizumab treatment should exceed 4 weeks to avoid additional risk of mortality whether patients receiving elective or emergent operation. Patients who received emergent operation within 28 days of bevcizumab infusion had the highest risk of mortality.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Bevacizumab , Neoplasias Colorretais/patologia , Tempo de Internação , Estudos Retrospectivos
20.
Nutrients ; 15(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37447297

RESUMO

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Cetuximab/efeitos adversos , Estudos Retrospectivos , Neoplasias Colorretais/tratamento farmacológico , Pontuação de Propensão , Neoplasias do Colo/tratamento farmacológico , Nutrição Parenteral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
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