RESUMO
BACKGROUND: The significance of resection of paraaortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after paraaortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. PATIENTS: Patients with resected and pathologically proven paraaortic lymph node metastasis of CRC between 2010 and 2015. DATA SOURCES: Database and medical records at each institution. MAIN OUTCOME MEASURES: Overall survival after paraaortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of paraaortic lymph node metastasis. RESULTS: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% confidence interval [CI]) was 41.0% (32.0, 49.8), and the median survival (95% CI) was 4.1 (3.4, 4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs. pT1- 3, adjusted hazard ratio [aHR]: 1.91, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.98, p = 0.005), time to metastases (synchronous vs. metachronous, aHR: 2.02, p = 0.02), and number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5, 29.7), with a median (95% CI) of 1.2 (0.9, 1.4) years. The primary tumor location (left- vs. right-sided colon, aHR: 4.77, p = 0.01; rectum vs. right-sided colon, aHR: 5.27, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.90, p = 0.03), number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.20, p = 0.001), and hospital volume (<10 vs. ≥10, aHR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Paraaortic lymph node recurrence was the most common at 33.3%. LIMITATIONS: Selection bias cannot be ruled out because of the retrospective nature of the study. CONCLUSIONS: Less than three paraaortic lymph node metastasis was a favorable prognostic factor for both overall survival and recurrence-free survival. However, paraaortic lymph node metastases were considered to be a systemic disease and the significance of resection was limited. See Video Abstract.
RESUMO
When pancreatic head cancer invades the superior mesenteric artery (SMA), attempts at curative resection are aborted. Preoperative imaging diagnostics to determine the surgical curability have yet to surpass the intraoperative information acquired via inspection, palpation, and trial dissection. Pancreatoduodenectomy (PD) is a standard measure for treating periampullary cancers. In conventional PD, SMA invasion is usually identified by dissecting the retroportal lamina, which connects the uncinate process and SMA nerve plexus after dividing the neck of the pancreas. During PD for pancreatic head cancer, this retroperitoneal margin frequently vitiates surgical curability. SMA-first approaches during PD are methods where the SMA is dissected first by severing the posterior pancreatic capsule to assess the SMA involvement of pancreatic cancer early in the operation. The first report of such an approach prompted subsequent reports of various maneuvers that are now known collectively as "artery-first" approaches. We herein review those approaches by classifying them according to (1) the side of the mesocolon from where the SMA approach occurs (supracolic or infracolic) and (2) the direction of access (right or left and anterior or posterior). The steps of the reported PD procedures are numbered according to a timeline and summarized using anatomical division of the SMA.
Assuntos
Artéria Mesentérica Superior/anatomia & histologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Neoplasias Vasculares/irrigação sanguínea , Neoplasias Vasculares/patologia , Humanos , Invasividade Neoplásica , Neoplasias Pancreáticas/irrigação sanguíneaRESUMO
Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate lysophospholipid levels in colorectal cancer tissues to identify lysophospholipids, the levels of which change specifically in colorectal cancers. We used liquid chromatography-tandem mass spectrometry to measure lysophospholipid levels in cancerous and normal tissues from 11 surgical specimens of sigmoid colon cancers, since recent advances in this field have improved detection sensitivities for lysophospholipids. Our results indicate that, in colon cancer tissues, levels of lysophosphatidylinositol and lysophosphatidylserine were significantly higher ( p = 0.025 and p = 0.01, respectively), whereas levels of lysophosphatidic acid were significantly lower ( p = 0.0019) than in normal tissues. Although levels of lysophosphatidylglycerol were higher in colon cancer tissues than in normal tissues, this difference was not found to be significant ( p = 0.11). Fatty acid analysis further showed that 18:0 lysophosphatidylinositol and 18:0 lysophosphatidylserine were the predominant species of lysophospholipids in colon cancer tissues. These components may be potentially involved in colorectal carcinogenesis.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Lisofosfolipídeos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
PURPOSE: Most elderly patients with colorectal cancer have comorbidities and reduced functional reserve, which may increase their risks of postoperative morbidity and mortality, and subsequently influence the treatment choice. Therefore, this study aimed to investigate the treatment choice and compare laparoscopic and open surgery in this setting. METHODS: This retrospective study evaluated 118 patients with colorectal cancer (≥ 85 years old between January 2007 and February 2018) to determine the influence of comorbidities on treatment choice, as well as the safety and feasibility of laparoscopic surgery for these patients. RESULTS: The patients included 42 men (35.6%) and 106 patients (89.8%) with comorbidities. The treatments were curative resection for 90 patients and palliative surgery for 16 patients, including 5 cases of colostomy/ileostomy because of the difficulty of primary cancer resection, pneumonia, or pulmonary hypertension. Twelve patients received non-surgical treatment, including 7 patients with decreased respiratory function because of chronic obstructive pulmonary disease or pneumonia. Forty-three patients underwent open curative resection and 47 patients underwent laparoscopic curative resection, which was associated with a significantly shorter hospital stay (14 days vs. 19days, P < 0.01), a lower morbidity rate (17.0% vs. 37.2%, P = 0.035), and less blood loss (10 mL vs. 140 mL, P < 0.01). One patient in each group died during the postoperative period because of worsened pre-existing pneumonia. CONCLUSION: Laparoscopic surgery was safer and less invasive than open surgery for colorectal cancer among ≥ 85-year-old patients. Pulmonary comorbidities affected the choice of non-curative surgery and may be related to the risk of postoperative mortality.
Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Pneumopatias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
Many long noncoding RNAs (lncRNAs) are reported to be dysregulated in human cancers and play critical roles in tumor development and progression. Furthermore, it has been reported that many lncRNAs regulate gene expression by recruiting chromatin remodeling complexes to specific genomic loci or by controlling transcriptional or posttranscriptional processes. Here we show that an lncRNA termed UPAT [ubiquitin-like plant homeodomain (PHD) and really interesting new gene (RING) finger domain-containing protein 1 (UHRF1) Protein Associated Transcript] is required for the survival and tumorigenicity of colorectal cancer cells. UPAT interacts with and stabilizes the epigenetic factor UHRF1 by interfering with its ß-transducin repeat-containing protein (TrCP)-mediated ubiquitination. Furthermore, we demonstrate that UHRF1 up-regulates Stearoyl-CoA desaturase 1 and Sprouty 4, which are required for the survival of colon tumor cells. Our study provides evidence for an lncRNA that regulates protein ubiquitination and degradation and thereby plays a critical role in the survival and tumorigenicity of tumor cells. Our results suggest that UPAT and UHRF1 may be promising molecular targets for the therapy of colon cancer.
Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Neoplasias do Colo/genética , RNA Longo não Codificante/fisiologia , Proteínas Estimuladoras de Ligação a CCAAT/química , Linhagem Celular Tumoral , Epigênese Genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteólise , Ubiquitina-Proteína Ligases , Ubiquitinação , Regulação para CimaRESUMO
Rectal gastrointestinal stromal tumor (GIST) is a rare entity. Thus, its clinical features have not been well documented, and optimal treatment strategies have not been established. Surgery for rectal GISTs may be difficult because they are often large in size. In addition, rectal GISTs were found to be associated with high rates of local recurrence, regardless of the surgical procedure, before imatinib was introduced in the early 2000s. Since the introduction of imatinib therapy, accumulating evidence suggests that neoadjuvant imatinib therapy may improve the outcomes of rectal GIST treatment. Neoadjuvant imatinib therapy for rectal GISTs offers a number of potential benefits, including tumor downsizing, reduction in mitotic activity, reduced morbidity, and a reduced risk of recurrence. Less radical procedures may allow for the preservation of the anal sphincter and avoidance of a permanent colostomy. This review summarizes the current status and future perspectives of neoadjuvant imatinib therapy for the treatment of rectal GISTs.
Assuntos
Antineoplásicos/administração & dosagem , Tumores do Estroma Gastrointestinal/terapia , Mesilato de Imatinib/administração & dosagem , Terapia Neoadjuvante , Neoplasias Retais/terapia , Canal Anal , Procedimentos Cirúrgicos do Sistema Digestório , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mutação , Recidiva Local de Neoplasia , Tratamentos com Preservação do Órgão/métodos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Neoplasias Retais/genética , Neoplasias Retais/patologia , Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: A hypoxic environment exists in most solid tumors because in rapidly growing tumors, the development of angiogenic vasculature is heterogenous, usually not enough to overcome the necessary oxygen supply. In an ischemic condition, cancer cells develop escape mechanisms to survive and leave the unfavorable environment. That result in the acquisition of increased potential for local invasion and evasion to distant organs. However, the escape mechanisms of cancer cells from hypoxic stress have not been fully characterized. MATERIALS AND METHODS: The human colon cancer cell line LoVo was cultured in hypoxia, and the adhesive and migratory properties were analyzed. The expression of cell surface and cytoplasmic molecules was also investigated. RESULTS: Under hypoxic conditions, cells developed epithelial-mesenchymal transition. The expression levels of α2, α5, and ß1 integrins were significantly upregulated and, as a consequence, the ability to adhere to and migrate on collagen and fibronectin was increased. On the other hand, the expression of 67-kDa laminin receptor and the abilities to adhere to and migrate on laminin were decreased. Additionally, the expression of CXCR4 was significantly increased on cells cultured in hypoxia, and the chemotactic activity to stromal cell-derived factor 1α was remarkably increased. CONCLUSIONS: Hypoxic stress induced active epithelial-mesenchymal transition in colon cancer cells, with the typical morphologic and functional changes. These morphologic and functional changes of ß1 integrins, the 67-kDa laminin receptor, and CXCR4 may be essential for the acquisition of the invasive and metastatic features in colorectal cancer.
Assuntos
Adenocarcinoma/patologia , Movimento Celular/fisiologia , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/fisiologia , Hipóxia/fisiopatologia , Adenocarcinoma/metabolismo , Adenocarcinoma/fisiopatologia , Linhagem Celular Tumoral , Quimiocina CXCL12/metabolismo , Colágeno/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Fibronectinas/metabolismo , Humanos , Técnicas In Vitro , Integrinas/metabolismo , Invasividade Neoplásica/fisiopatologia , Receptores CXCR4/metabolismo , Receptores de Laminina/metabolismoRESUMO
BACKGROUND: The aim of this study was to assess whether the neutrophil to lymphocyte ratio (NLR) and other laboratory markers may predict the prognosis of advanced colorectal cancer (CRC) patients receiving palliative chemotherapy. METHODS: The study population included 50 patients with far advanced or recurrent unresectable CRC who received oxaliplatin-based combination chemotherapy as first-line treatment in our hospital between June 2005 and November 2010. Seven clinical variables and 7 laboratory indices before chemotherapy were evaluated retrospectively as the possible prognostic factors of overall and progression-free survival. RESULTS: During the study period, 27 patients (54%) died of CRC. Elevated NLR (≥4.0) was observed in 15 patients (30%). By univariate analysis, elevated NLR, performance status and hypoalbuminemia were significantly associated with both poor overall and progression-free survivals. Multivariate analysis showed that elevated NLR (hazard ratio 4.39, 95% confidence interval 1.82-10.7; p = 0.0013) and thrombocytosis (hazard ratio 5.02, 95% confidence interval 1.69-13.4; p = 0.0066) were independently associated with overall survival. CONCLUSION: Elevated NLR is a powerful predictor of poor response to oxaliplatin-based chemotherapy in patients with unresectable CRC. The ratio is a simply accessible and inexpensive but useful biomarker in CRC patients receiving chemotherapy.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Linfócitos , Neutrófilos , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Oxaliplatina , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
Autophagy is a complex of adaptive cellular response that enhances cancer cell survival in the face of cellular stresses such as chemotherapy. Recently, chloroquine diphosphate (CQ), a widely used antimalarial drug, has been studied as a potential inhibitor of autophagy. Here, we aimed to investigate the role of CQ in potentiating the effect of 5-fluorouracil (5-FU), the chemotherapeutic agent of first choice for the treatment of colorectal cancer, in an animal model of colon cancer. The mouse colon cancer cell line colon26 was used. For the in-vivo study, colon26 cells were injected subcutaneously into BALB/c mice, which were treated with saline as a control, CQ (50 mg/kg/day), 5-FU (30 mg/kg/day), or the combination therapy (CQ plus 5-FU). The tumor volume ratio and body weight were monitored. After the sacrifice, tumor tissue protein extracts and tumor sections were prepared and subjected to immunoblotting for the analysis of autophagy-related and apoptosis-related proteins, and the terminal transferase uridyl end labeling assay. The combination of CQ resulted in the inhibition of 5-FU-induced autophagy and a significant enhancement in the 5-FU-induced inhibition of tumor growth. Furthermore, the combination treatment of CQ and 5-FU resulted in a significant increase in the ratio of apoptotic cells compared with other treatments. The expression levels of the proapoptotic proteins, namely Bad and Bax, were increased by the CQ treatment in the protein extracts from tumors. Our findings suggest that the combination therapy of CQ and 5-FU should be considered as an effective strategy for the treatment of colorectal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autofagia/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cloroquina/administração & dosagem , Cloroquina/análogos & derivados , Cloroquina/farmacologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , RNA Nucleotidiltransferases/efeitos dos fármacos , RNA Nucleotidiltransferases/metabolismo , Fator de Transcrição TFIIH , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND AND AIM: Recently, the cancer stem cells (CSCs) theory has been proposed, and CD133 has been suggested as a potential marker of CSCs in various cancer types. In the present study, we aimed evaluate CD133 as a potential marker of colorectal CSCs and, for this purpose, isolated CD133(+) and CD133(-) cells from a single colorectal cancer cell line, and compared their features, especially related to the tumor-forming and differentiation abilities, and the sensitivity to chemotherapy. METHODS AND RESULTS: CD133(+) cells had higher in vivo tumor-forming ability than CD133(-) cells, and in culture, they progressively differentiated into CD133(-) cells, but not vice-versa. On the other hand, CD133(-) cells were more resistant to 5-fluorouracil (FU) treatment than CD133(+) cells, and it was found to be dependent on the higher expression of ß1-integrins, and consequently, higher ability to bind collagen. Disruption of the ß1-integrin function abrogated the chemoresistance. CONCLUSION: From the present results, we concluded that colorectal cancer CD133(+) cells, although showing some features of CSCs, are not more resistant to 5-FU than CD133(-) cells. Therefore, definite conclusions can not be drawn yet, but it is strongly suggestive that CD133 should not be used as a single CSC marker of colorectal cancer.
Assuntos
Antígenos CD/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/imunologia , Fluoruracila/uso terapêutico , Glicoproteínas/deficiência , Glicoproteínas/metabolismo , Integrina beta1/fisiologia , Peptídeos/deficiência , Peptídeos/metabolismo , Transdução de Sinais/fisiologia , Antígeno AC133 , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma/fisiopatologia , Antígenos CD/genética , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose/fisiologia , Biomarcadores Tumorais/imunologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/fisiopatologia , Glicoproteínas/genética , Humanos , Peptídeos/genética , Resultado do TratamentoRESUMO
The standard treatment for colorectal cancer has always been surgery and chemotherapy, which may be used in combination to treat patients. Immune checkpoint inhibitors have been a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair. However, little information is available about their use in neoadjuvant and conversion settings with only a few case reports and only one phase 2 trial. The present study reports the case of a large, locally advanced right-sided metastatic deficient mismatch repair/microsatellite instability-high colon cancer, which showed a pathological complete response after combination treatment with nivolumab and ipilimumab. To the best of our knowledge, resected metastatic colon cancer with a pathological complete response after treatment using dual immune checkpoint inhibitors has not been previously reported. Overall, this case report suggests the use of immune checkpoint inhibitors before colorectal surgery.
RESUMO
BACKGROUND: Sulforaphane (SUL), a kind of isothiocyanate, has recently been focused due to its strong pro-apoptotic effect on cancer cells as well as tumor vascular endothelial cells (ECs). And recently, we demonstrated the induction of autophagy by colon cancer cells as a protective mechanism against SUL. In the present study, we aimed to investigate the possible role of autophagy induction by ECs as a defense mechanism against SUL. METHODS: Human umbilical vein endothelial cells (HUVECs) were used as the in vitro model of angiogenic ECs. The induction of autophagy was evaluated by the detection of acidic vesicular organelles (AVOs) by flow-cytometry, after the staining with acridine orange, as well as the detection of light chain 3(LC3) by Western blot. Finally, the functional implication of autophagy inhibition and SUL treatment in ECs was investigated by their ability to form vascular-like structures on Matrigel. RESULTS: Treatment of HUVECs with relatively low concentrations of SUL for 16 h resulted in the evident formation of AVOs and the recruitment of LC3 to autophagosomes, the pathognomonic features of autophagy. Co-treatment of cells with the specific autophagy inhibitor (3-methyladenine) potentiated the proapoptotic effect of SUL. And inhibition of autophagy potentiated the inhibitory effect of SUL on the ability of ECs to form capillary-like structures. CONCLUSION: Similar to cancer cells, ECs induced autophagy in response to the pro-apoptotic agent, SUL, and the inhibition of autophagy potentiated the pro-apoptotic effect. These findings open premises for the use of autophagy inhibitors in combination with anti-angiogenic agents.
Assuntos
Inibidores da Angiogênese/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Tiocianatos/farmacologia , Western Blotting , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/enzimologia , Citometria de Fluxo , Humanos , Isotiocianatos , Proteínas Associadas aos Microtúbulos/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Organelas/efeitos dos fármacos , Organelas/metabolismo , Sulfóxidos , Veias Umbilicais/citologiaRESUMO
BACKGROUND: Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. METHODS: HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. RESULTS: 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21Cip1 and p27Kip1 and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU. CONCLUSION: Our findings suggest that the combination therapy with CQ should be a novel therapeutic modality to improve efficacy of 5-FU-based chemotherapy, possibly by inhibiting autophagy-dependent resistance to chemotherapy.
Assuntos
Antimaláricos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cloroquina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Autofagia , Western Blotting , Ciclo Celular , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Ensaio de Unidades Formadoras de Colônias , Sinergismo Farmacológico , Citometria de Fluxo , Fluoruracila/uso terapêutico , Humanos , Técnicas ImunoenzimáticasRESUMO
BACKGROUND: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer. MATERIALS AND METHODS: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared. RESULTS: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC. CONCLUSION: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer.
Assuntos
Colite Ulcerativa/complicações , Colite Ulcerativa/genética , Neoplasias Colorretais/etiologia , Genes Mitocondriais , Polimorfismo Genético , Transformação Celular Neoplásica/genética , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Suscetibilidade a Doenças , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , MutaçãoRESUMO
BACKGROUND: We aimed to investigate the molecular features of synchronous colorectal cancer (CRC). MATERIALS AND METHODS: Out of 1,262 patients with CRC, 130 lesions in 59 patients with synchronous CRC were retrospectively analyzed. Microsatellite, v-Ki-Ras2 Kristen rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), tumor protein 53 (TP53) and ß-catenin status were evaluated and compared between synchronous CRC lesions in each patient. RESULTS: The subtypes of instability, BRAF and ß-catenin subtypes was significant but low. Patients with discordant KRAS and TP53 were not concordant between lesions in the same patient, and concordance of microsatellite KRAS/BRAF subtypes comprised 50.8% of those with synchronous CRC. The rate of patients with lesions containing both mutL homolog 1 (MLH1) methylation and microsatellite stable status was 66.7% in those with synchronous CRC, with at least one lesion with high microsatellite instability. CONCLUSION: The present study on synchronous CRC demonstrated a low concordance of molecular subtypes between lesions in the same patient. A molecular analysis of metastatic lesions is warranted for molecular targeted therapy of metastatic synchronous CRC.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Colorectal surgery is associated with a high risk of perioperative venous thromboembolism (VTE), and this risk is especially high following colorectal cancer resection and surgery for inflammatory bowel disease. Previous analyses of large databases have reported the incidence of postoperative VTE in this population to be approximately 1.1%-2.5%. Therefore, to minimize this risk, patients should be offered appropriate prophylaxis, which may involve a combination of mechanical and pharmacologic prophylaxis with low-dose unfractionated heparin or low molecular weight heparin as recommended by several guidelines. Prior to initiation of treatment, appropriate risk stratification should be performed according to the patients' basic and disease-related as well as procedure-related risk factors, and post-operative factors. Furthermore, a risk-benefit calculation that takes into account patients' VTE and bleeding risk should be performed prior to starting pharmacologic prophylaxis and to help determine the duration of treatment.
Assuntos
Colo/cirurgia , Neoplasias Colorretais/cirurgia , Doenças Inflamatórias Intestinais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Reto/cirurgia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Idoso , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Heparina/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Guias de Prática Clínica como Assunto , Medição de Risco , Fatores de Risco , Tromboembolia Venosa/etiologiaRESUMO
PURPOSE: Peritoneal carcinomatosis of colorectal cancer origin is associated with poor prognosis. With regard to ovarian, gastric, and pancreatic cancer, the safety and efficacy of intraperitoneal administration of paclitaxel (ip PTX) has been demonstrated. This drug can be administered easily and repeatedly through a catheter into the peritoneal cavity. In this phase I study, we evaluated the safety of ip PTX combined with 5-fluorouracil, folinic acid, oxaliplatin, and bevacizumab (mFOLFOX6-bevacizumab) or capecitabine, oxaliplatin, and bevacizumab (CapeOX-bevacizumab) for colorectal cancer with peritoneal metastasis. METHODS: Colorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20 mg/m2 of ip PTX was administered weekly, in combination with mFOLFOX6-bevacizumab or CapeOX-bevacizumab. Primary endpoint was the safety of the combination chemotherapy. RESULTS: Among the six patients enrolled, three received the mFOLFOX6-bevacizumab plus ip PTX regimen and three received the CapeOX-bevacizumab plus ip PTX regimen. Dose-limiting toxicity was not observed. Overall, grade 3 adverse events, such as leukopenia and neutropenia, were observed in two of three patients (66.7%) for each chemotherapeutic regimen, but no grade 4 adverse events were observed. Moreover, adverse events associated with the peritoneal access port, such as infection or occlusion of the catheter, were not observed. CONCLUSIONS: The adverse events of mFOLFOX6-bevacizumab or CapeOX-bevacizumab in combination with ip PTX were considered similar to those described in previous studies of oxaliplatin-based treatment alone. 1 year after the start of chemotherapy, the efficacy of ip PTX will be evaluated as a secondary outcome.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Paclitaxel/administração & dosagem , Segurança do Paciente , Neoplasias Peritoneais/secundário , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by thrombocytosis and a propensity for both thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Here, we report a case of colorectal cancer in an ET patient treated using laparoscopic ileocecal resection. CASE PRESENTATION: A 40-year-old woman was admitted to our hospital after presenting with liver dysfunction. She had been previously diagnosed with ET; aspirin and anagrelide had been prescribed. Subsequent examination at our hospital revealed cecal cancer. Distant metastasis was absent; laparoscopic ileocecal resection was performed. Anagrelide was discontinued only on the surgery day. She was discharged on the seventh postoperative day without thrombosis or hemorrhage. However, when capecitabine and oxaliplatin were administered as adjuvant chemotherapy with continued anagrelide administration, she experienced hepatic dysfunction and thrombocytopenia; thus, anagrelide was discontinued. Five days later, her platelet count recovered. Subsequently, anagrelide and aspirin administration was resumed, without any adjuvant chemotherapy. Her liver function normalized gradually in 4 months. One-year post operation, she is well without tumor recurrence or new metastasis. CONCLUSIONS: To our knowledge, this is the first report of laparoscopic colectomy performed on an ET patient receiving anagrelide. Our report shows that complications such as bleeding or thrombosis can be avoided by anagrelide administration. Contrastingly, thrombocytopenia due to anagrelide intake should be considered when chemotherapy that could cause bone marrow suppression is administered.
RESUMO
AIM: This study aimed to clarify the difference in the clinicopathological and prognostic features between synchronous colorectal cancer (CRC) and solitary CRC. MATERIALS AND METHODS: A retrospective analysis was conducted in patients with synchronous and solitary CRC. RESULTS: A total of 92 (7.1%) out of 1,295 consecutive patients had synchronous CRC. Mucinous adenocarcinoma was more frequent in patients with synchronous CRC than in those with solitary CRC (13.0% vs. 3.7%; p<0.001). The 5-year relapse-free survival (RFS) rate was poorer in patients with synchronous CRC than in those with solitary CRC (65.3% vs. 75.1%; p=0.035), which was contrived by the multivariate analysis (hazard ratio=1.52(HR); p=0.039). CONCLUSION: Patients with synchronous CRC had a poorer RFS than those with solitary CRC; thus, patients with synchronous CRC might require more intensive care than those with solitary CRC in follow-up.
Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Primárias Múltiplas/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The revised Bethesda guidelines (rBG) are generally used for screening of Lynch syndrome, and few researchers have investigated the associations between microsatellite instability (MSI) status and each item of the rBG. PATIENTS AND METHODS: This retrospective study included patients with colorectal cancer who were classified into those fulfilling the rBG (Bethesda group) and those not (control group). The breakdown of each item in the rBG and predictors of high MSI (MSI-H) were determined in the Bethesda group. RESULTS: Of 809 consecutive patients, 161 (19.9%) were found to fulfil the rBG criteria. As a predictor of MSI-H, items 2 or 5 of the rBG showed a sensitivity of 93.3%. Item 5 and right-sided tumour location were independent predictors of MSI-H in patients fulfilling the rBG (odds ratio(OR)=4.49 and 25.1; p=0.0260 and <0.0001, respectively). CONCLUSION: Item 5 of the rBG and right-sided tumour location are significant predictors of MSI-H.