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1.
Gan To Kagaku Ryoho ; 50(13): 1647-1649, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38303370

RESUMO

A 74-year-old male presenting with bloody stools was diagnosed with advanced rectal cancer. He underwent robot- assisted low anterior resection and temporary ileostomy. Cefmetazole(CMZ)was administered during surgery and on postoperative day(POD)1. His postoperative course was generally good. On POD8, he developed abdominal fullness, vomiting, renal dysfunction, and hyperkalemia. Plain CT revealed small bowel ileus and outlet obstruction with ileostomy was suspected. A nasogastric tube was placed in the stomach, and a balloon catheter was inserted from the ileostomy to the oral side of the ileum. The patient went into shock on the same day and was transferred to a high-care unit. Contrast-enhanced CT indicated pneumatosis intestinalis of the small bowel and portal venous gas. However, the wall of the small bowel was enhanced, so the patient was observed carefully without attempting an operation. The patient's condition improved with systemic management. On POD10, a stool culture from the ileostomy tested positive for CD toxin. Clostridium difficile enteritis(CDE)was diagnosed. The condition improved with systemic control. On POD52, paralytic ileus recurred, and his stool tested positive for the CD toxin again. The ileus improved with conservative treatment. On POD70, the patient was transferred to the hospital for rehabilitation. We report a case of CDE with ileostomy for rectal cancer surgery.


Assuntos
Clostridioides difficile , Enterite , Íleus , Neoplasias Retais , Masculino , Humanos , Idoso , Ileostomia , Recidiva Local de Neoplasia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Íleus/etiologia , Íleus/cirurgia , Enterite/diagnóstico , Enterite/cirurgia
2.
Int J Surg Case Rep ; 71: 290-293, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32480340

RESUMO

INTRODUCTION: Currently, the frequency of evaluating the flow of a reconstructed gastric tube using indocyanine green (ICG) fluorescence has been increasing. However, it has been difficult to decide on the operation method for patients with gastric tube cancer (GTC). We herein report a case in which ICG was effective in a patient with resection of GTC. PRESENTATION OF CASE: An 83-year-old man underwent subtotal esophagectomy with gastric tube reconstruction via the retrosternal route for esophageal cancer and right hemicolectomy for ascending colon cancer 16 years earlier. Postoperatively, the proximal part of the gastric tube had poor blood flow. Therefore, the patient underwent proximal-side resection of the gastric tube. Thereafter, free jejunal graft reconstruction was performed. The patient had not developed recurrence at that point. Recently, the patient visited the hospital complaining of nausea and chest discomfort. Upper gastrointestinal endoscopy revealed a type 0-IIa + IIc lesion located around the pylorus. A biopsy showed adenocarcinoma. Based on these findings, the patient was diagnosed with gastric tube cancer (cT1bN0M0StageI). The invasion depth of the cancer was predicted to be widespread submucosal invasion. Therefore, the patient underwent surgery. Intraoperatively, we evaluated the flow of the gastric tube after clamping the right gastroepiploic artery using ICG fluorescence. As a result, the flow of the gastric tube was deemed insufficient. Consequently, subtotal gastrectomy was performed with preservation of the right gastroepiploic artery via Roux-en-Y reconstruction. DISCUSSION: ICG fluorescence is useful for evaluating the flow of the gastric tube helping to decide the operating method. CONCLUSION: We herein report a case of subtotal gastrectomy for GTC using intraoperative ICG fluorescence.

3.
Int J Cancer ; 147(2): 532-541, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32191346

RESUMO

Tertiary lymphoid structures (TLSs) provide an immunological antineoplastic effect. Recent evidences link a unique 12-chemokine (CCL2, -3, -4, -5, -8, -18, -19, -21, CXCL9, -10, -11, -13) signature status from tumor tissue and the TLS expression. However, the potential significance of 12-chemokine signature status for clinical use is unknown. We aimed to evaluate the association of 12-chemokine signature status with patient outcomes in colorectal cancer (CRC). We used integrated data of resected 975 CRC cases within three independent cohorts from France, Japan and the United States (GSE39582, KUMAMOTO from Kumamoto university hospital and TCGA). The association of 12-chemokine signature status with clinicopathological features, patient outcome, TLS expression status and key tumor molecular features was analyzed. Patients with low 12-chemokine signature status had a significant shorter relapse-free survival in discovery cohort (HR: 1.61, 95% CI: 1.11-2.39, p = 0.0123), which was confirmed in validation cohort (HR: 3.31, 95% CI: 1.33-10.08, p = 0.0087). High 12-chemokine signature status had significant associations with right-sided tumor, high tumor-localized TLS expression, BRAF mutant, CIMP-high status and MSI-high status. Furthermore, RNA-seq based analysis showed that high 12-chemokine signature status was strongly associated with inflammation-related, immune cells-related and apoptosis pathways (using gene set enrichment analysis), and more tumor-infiltrating immune cells, such as cytotoxic T lymphocytes and myeloid dendritic cells (using MCP-counter analysis). We investigated a promising effect of 12-chemokine signature status in CRC patients who underwent resection. Our data may be helpful in developing novel immunological treatment strategies for CRC.


Assuntos
Biomarcadores Tumorais/genética , Quimiocinas/genética , Neoplasias Colorretais/cirurgia , Estruturas Linfoides Terciárias/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Bases de Dados Genéticas , Feminino , França , Regulação Neoplásica da Expressão Gênica , Humanos , Japão , Masculino , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Estados Unidos
4.
Gan To Kagaku Ryoho ; 46(1): 127-129, 2019 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-30765663

RESUMO

A 79-year-old man was diagnosed with Stage ⅢB(T4N2M0)adenocarcinoma of the lung, administered. He suddenly developed abdominal pain with muscle guarding and rebound tenderness. An abdominal computed tomography scan revealed a thickened small bowel wall and mesenteric mass, as well as massive ascites and free air. He underwent an emergency laparotomy following a diagnosis of pan-peritonitis due to intestinalperforation. A partialresection of the smallintestine and abdominal drainage were performed. The resected specimen included an ulcerative lesion on the mucosal surface. The pathological diagnosis was a metastasis of lung cancer. The patient died in hospice 29 days postoperatively. In the present case, however, surgery improved the patient's quality of life. Although lung cancer metastasis to the small bowel is associated with a poor prognosis, palliative surgery is indicated in otherwise fatal circumstances.


Assuntos
Adenocarcinoma de Pulmão , Perfuração Intestinal , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Idoso , Humanos , Perfuração Intestinal/etiologia , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica , Qualidade de Vida
5.
Gan To Kagaku Ryoho ; 46(13): 2303-2305, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-32156912

RESUMO

Laparoscopy and endoscopy cooperative surgery(LECS)is a surgical technique to resect a tumor with minimal invasion, using both a laparoscope and endoscope. Twenty-eight surgeries for gastric submucosal tumors(SMT)were performed between 2009 and 2019. Seven of those cases were performed using LECS. Two male and 5 female patients underwent LECS; their mean age was 53 years. The tumors were located at the anterior wall of the fornix in 1 case, anterior wall of the subcardia in 2 cases, anterior wall of the upper gastric body in 3 cases, and anterior wall of the lower gastric body in 1 case. Two cases were intraductal growing types, and 5 cases were intramural growing types. No postoperative complications have occurred. The mean size of the tumors was 21.1 mm. In pathological findings, 5 cases were gastrointestinal stromal tumor (GIST); 1 case was high risk, 2 cases were low risk, and 1 case was very low risk as classified using the modified-Fletcher's classification. Imatinib was administered to the high risk case, and there have been no recurrences in any cases.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Laparoscopia , Feminino , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Resultado do Tratamento
6.
Gan To Kagaku Ryoho ; 46(13): 2005-2007, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-32157041

RESUMO

A63 -year-old man complaining of anal pain visited our hospital. Three years 6 months previously, the patient underwent endoscopic submucosal dissection(ESD)for early-stage rectal cancer. Based on the pathological findings, adenocarcinoma with invasion to the submucosal layer(2,000 mm)and lymphovascular invasion were diagnosed. Abdominal computed tomography( CT)revealed a solid tumor 50mm in diameter and hematoma measuring approximately 90mm in length adjoining the tumor in the mesorectum. We performed exploratory laparoscopy. Ahematoma was confirmed in the mesentery from the sigmoid colon and rectum. After the surgery, endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)revealed well-differentiated adenocarcinoma. We diagnosed a hematoma associated with mesenteric recurrence following ESD for rectal cancer. The patient received chemotherapy first because of the large size of the recurrent cancer. Four courses of mFOLFOX6(5-FU: bolus 400mg/m / / / 2,2,400mg/m2,oxaliplatin 85 mg/m2) and panitumumab(6 mg/kg)were administered. Based on the CT findings following chemotherapy, the hematoma had disappeared, and the size of the recurrent cancer in the mesorectum reduced to 28 mm. The patient underwent laparoscopic lower anterior resection with D3 lymph node dissection and ileostomy. The postoperative course was uneventful. Currently, the patient has no recurrence.


Assuntos
Hematoma/cirurgia , Recidiva Local de Neoplasia , Neoplasias Retais , Terapia Combinada , Humanos , Masculino , Mesentério , Pessoa de Meia-Idade , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Reto
7.
Oncol Lett ; 16(4): 5275-5281, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214616

RESUMO

The adenoma-carcinoma sequence, the sequential mutation and deletion of various genes by which colorectal cancer progresses, is a well-established and accepted concept of colorectal cancer carcinogenesis. Proteins of the polycomb repressive complex 2 (PRC2) function as transcriptional repressors by trimethylating histone H3 at lysine 27; the activity of this complex is essential for cell proliferation and differentiation. The histone methyltransferase enhancer of zeste homolog 2 (EZH2), an essential component of PRC2, is associated with the transcriptional repression of tumor suppressor genes. EZH2 expression has previously been reported to increase with the progression of pancreatic intraductal papillary mucinous neoplasm. Thus, we hypothesized that EZH2 expression also increases during the adenoma-carcinoma sequence of colorectal cancer. The present study investigated changes in EZH2 expression during the colorectal adenoma-carcinoma sequence. A total of 47 patients with colorectal adenoma, 20 patients with carcinoma in adenoma and 43 patients with colorectal carcinoma who underwent surgical or endoscopic resection were enrolled in this study. Non-cancerous tissue from the clinical specimens was also examined. The association between EZH2 expression, pathology and expression of tumor suppressor genes during colorectal carcinogenesis were analyzed. Each specimen was immunohistochemically stained for EZH2, proliferation marker protein Ki-67 (Ki-67), cyclin-dependent kinase inhibitor (CDKN) 1A (p21), CDKN1B (p27) and CDKN2A (p16). Total RNA was extracted from formalin-fixed paraffin-embedded blocks and reverse transcription-quantitative polymerase chain reaction analysis of these genes was performed. Ki-67 and EZH2 expression scores increased significantly during the progression of normal mucosa to adenoma and carcinoma (P=0.009), and EZH2 expression score was positively associated with Ki-67 expression score (P=0.02). Conversely, p21 mRNA and protein expression decreased significantly, whereas expression of p27 and p16 did not change significantly. During the carcinogenesis sequence from normal mucosa to adenoma and carcinoma, EZH2 expression increased and p21 expression decreased significantly. EZH2 may therefore contribute to the development of colorectal cancer from adenoma via suppression of p21.

8.
Surg Today ; 48(7): 667-672, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29468435

RESUMO

PURPOSE: Surgery remains the curative treatment of choice for colorectal cancer (CRC). However, to our knowledge, no report has addressed the usefulness of additional regional lymph node dissection for primary CRC that has invaded another colon region. METHODS: We reviewed the clinicopathological characteristics and outcomes of eight patients who underwent surgery between March, 2005 and August, 2014, for CRC that invaded another region of the colon. RESULTS: Five patients underwent additional regional lymph node dissection in the area of the invaded colon and one patient had lymph node metastasis in the region. Two of three patients who did not undergo additional regional lymph node dissection were found to have regional lymph node recurrences in the area during the follow-up period. Although there was no statistical correlation between extra-regional lymph node metastasis and clinicopathological or operative factors, the patients with extra-regional lymph node metastasis or recurrence had primary regional lymph node metastasis. CONCLUSION: For curative intent, surgeons may need to perform additional regional lymph node dissection for primary CRC invading another colon region.


Assuntos
Colo/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Excisão de Linfonodo , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico por imagem , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do Tratamento
9.
Gan To Kagaku Ryoho ; 45(13): 2223-2225, 2018 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-30692338

RESUMO

A 73 -year-old man was found to have a mesenteric tumor on abdominal ultrasonography and computed tomography (CT). Single-port laparoscopic surgery using an umbilical ZigZag incision was performed. Operative findings revealed that the tumor involved the mesentery. The tumor and a section of small intestines were resected. Pathological examination diagnosed follicular lymphoma. Single-port laparoscopic surgery using an umbilical ZigZag incision is superior for manipulation of forceps and evisceration. This operative method may be useful for resection or biopsy of mesenteric tumors.


Assuntos
Neoplasias Intestinais , Laparoscopia , Linfoma , Idoso , Humanos , Neoplasias Intestinais/cirurgia , Intestino Delgado , Linfoma/cirurgia , Masculino , Mesentério
10.
Int Cancer Conf J ; 7(2): 40-42, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31149512

RESUMO

Rectal gastrointestinal stromal tumor (GIST) is comparatively rare and usually already large when detected. As resection is the main therapy for patients with primary resectable GIST, the surgical procedure must be tailored to the tumor status. For GISTs of the lower rectum, laparoscopic low anterior resection or abdominoperineal resection is one of the procedures of choice. However, rectal tumor, including rectal GIST, can also be surgically treated using a variety of posterior approaches. Of these, para-sacral approach is both simple and less invasive, even for large rectal GISTs, and provides a good view of the operative field. Here, we describe our procedure for the surgical treatment of large GISTs of the lower rectum.

11.
Gastric Cancer ; 21(2): 204-212, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28656485

RESUMO

BACKGROUND: Controlling Nutritional Status (CONUT), as calculated from serum albumin, total cholesterol concentration, and total lymphocyte count, was previously shown to be useful for nutritional assessment. The current study investigated the potential use of CONUT as a prognostic marker in gastric cancer patients after curative resection. METHODS: Preoperative CONUT was retrospectively calculated in 416 gastric cancer patients who underwent curative resection at Kumamoto University Hospital from 2005 to 2014. The patients were divided into two groups: CONUT-high (≥4) and CONUT-low (≤3), according to time-dependent receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. RESULTS: CONUT-high patients were significantly older (p < 0.001) and had a lower body mass index (p = 0.019), deeper invasion (p < 0.001), higher serum carcinoembryonic antigen (p = 0.037), and higher serum carbohydrate antigen 19-9 (p = 0.007) compared with CONUT-low patients. CONUT-high patients had significantly poorer overall survival (OS) compared with CONUT-low patients according to univariate and multivariate analyses (hazard ratio: 5.09, 95% confidence interval 3.12-8.30, p < 0.001). In time-dependent ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 5-year OS than the neutrophil lymphocyte ratio, the Modified Glasgow Prognostic Score, or pStage. When the time-dependent AUC curve was used to predict OS, CONUT tended to maintain its predictive accuracy for long-term survival at a significantly higher level for an extended period after surgery when compared with the other markers tested. CONCLUSIONS: CONUT is useful for not only estimating nutritional status but also for predicting long-term OS in gastric cancer patients after curative resection.


Assuntos
Colesterol/sangue , Contagem de Linfócitos , Albumina Sérica/análise , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Intervalo Livre de Doença , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Resultado do Tratamento
12.
Surg Endosc ; 32(6): 2852-2858, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29273870

RESUMO

BACKGROUND: Pulmonary morbidities after esophagectomy are still common and are a major cause of surgery-related mortality. The relationship between minimally invasive esophagectomy (MIE) and pulmonary morbidities is not clear. The current study aimed to examine the incidence of pulmonary morbidities after MIE and to clarify the associated risk factors. METHODS: Between May 2011 and December 2016, 184 patients underwent MIE for esophageal cancer. Clinical data were prospectively collected and analyzed. Patient- and surgery-related factors, relating to pulmonary complications, were compared between the complicated and uncomplicated cases. RESULTS: The incidence of any pulmonary morbidity following MIE was 17.9%. Univariate analysis showed that past heavy smoking [Brinkman index (BI) ≥ 1000], presence of neoadjuvant therapy, advanced clinical stage (stage III, IV), and intraoperative bleeding ≥ 600 g were candidates for being postoperative pulmonary morbidity risk factors. Multivariate analysis suggested that BI ≥ 1000 and advanced clinical stage were independent risk factors for causing pulmonary morbidities. CONCLUSIONS: Past heavy smoking and advanced stage are independent risk factors for pulmonary morbidities after MIE. When performing MIE for such cases, various preoperative precautions and careful postoperative monitoring are necessary.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Toracoscopia/efeitos adversos , Idoso , Quilotórax/etiologia , Empiema Pleural/etiologia , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Hemorragia/etiologia , Humanos , Masculino , Análise Multivariada , Pneumonia/etiologia , Pneumotórax/etiologia , Complicações Pós-Operatórias , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório/etiologia , Insuficiência Respiratória/etiologia , Fatores de Risco , Fumar/efeitos adversos , Traqueostomia/estatística & dados numéricos
13.
Anticancer Res ; 38(1): 491-499, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29277814

RESUMO

AIM: This study aimed to clarify the predictive impact of visceral fat on response to bevacizumab in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Pretreatment computed tomography was used to measure visceral fat area (VFA) and patients with mCRC receiving first-line chemotherapy with/without bevacizumab were divided by median VFA value into two groups: high VFA and low VFA. RESULTS: In the bevacizumab-treated group, patients with low VFA had significantly shorter overall survival (OS) than patients with high VFA in univariate (median=21.1 vs. 38.9 months; hazard ratio=1.70, 95% confidence interval=1.06-2.70, p=0.03) and multivariate analysis (hazard ratio=1.85, 95% confidence interval=1.15-3.03, p=0.01). No significant differences were seen in OS between groups treated with chemotherapy alone. The VFA had a marginally significant modifying effect on the relationship between bevacizumab and OS (p for interaction=0.07). CONCLUSION: Our findings provide the first evidence that a low VFA might be a negative predictive marker for response to bevacizumab in patients with mCRC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Gordura Intra-Abdominal/fisiologia , Adulto , Idoso , Biomarcadores Tumorais/fisiologia , Camptotecina/uso terapêutico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Compostos Organoplatínicos/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
14.
Surg Oncol ; 26(4): 368-376, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29113654

RESUMO

More than 100 trillion microorganisms inhabit the human intestinal tract and play important roles in health conditions and diseases, including cancer. Accumulating evidence demonstrates that specific bacteria and bacterial dysbiosis in the gastrointestinal tract can potentiate the development and progression of gastrointestinal tract neoplasms by damaging DNA, activating oncogenic signaling pathways, producing tumor-promoting metabolites such as secondary bile acids, and suppressing antitumor immunity. Other bacterial species have been shown to produce short-chain fatty acids such as butyrate, which can suppress inflammation and carcinogenesis in the gastrointestinal tract. Consistent with these lines of evidence, clinical studies using metagenomic analyses have shown associations of specific bacteria and bacterial dysbiosis with gastrointestinal tract cancers, including esophageal, gastric, and colorectal cancers. Emerging data demonstrate that intestinal bacteria can modulate the efficacy of cancer chemotherapies and novel targeted immunotherapies such as anti-CTLA4 and anti-CD274 therapies, the process of absorption, and the occurrence of complications after gastrointestinal surgery. A better understanding of the mechanisms by which the gut microbiota influence tumor development and progression in the intestine would provide opportunities to develop new prevention and treatment strategies for patients with gastrointestinal tract cancers by targeting the intestinal microflora.


Assuntos
Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/prevenção & controle , Trato Gastrointestinal/microbiologia , Progressão da Doença , Microbioma Gastrointestinal , Neoplasias Gastrointestinais/epidemiologia , Humanos
15.
Oncol Lett ; 14(6): 6373-6378, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29151903

RESUMO

The human microbiome Fusobacterium nucleatum, which primarily inhabits the oral cavity, causes periodontal disease and has also been implicated in the development of colorectal cancer. However, whether F. nucleatum is present in other gastroenterological cancer tissues remains to be elucidated. The present study evaluated whether quantitative polymerase chain reaction (qPCR) assays were able to detect F. nucleatum DNA and measure the quantity of F. nucleatum DNA in esophageal, gastric, pancreatic and liver cancer tissues. The accuracy of the qPCR assay was determined from a calibration curve using DNA extracted from cells from the oral cavity. Formalin-fixed paraffin-embedded (FFPE) tumor tissues from 20 patients with gastroenterological [esophageal (squamous cell carcinoma), gastric, colorectal, pancreatic and liver] cancer and 20 matched normal tissues were evaluated for F. nucleatum DNA content. The cycle threshold values in the qPCR assay for F. nucleatum and solute carrier organic anion transporter family member 2A1 (reference sample) decreased linearly with the quantity of input DNA (r2>0.99). The F. nucleatum detection rate in esophageal, gastric and colorectal cancer tissues were 20% (4/20), 10% (2/20) and 45% (9/20), respectively. F. nucleatum was not detected in liver and pancreatic cancer tissues. The qPCR results from the frozen and FFPE tissues were consistent. Notably, F. nucleatum was detected at a higher level in superficial areas compared with the invasive areas. F. nucleatum in esophageal, gastric and colorectal cancer tissues was evaluated by qPCR using FFPE tissues. F. nucleatum may be involved in the development of esophageal, gastric and colorectal cancer.

16.
Stem Cells ; 35(9): 2027-2036, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28699179

RESUMO

The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. Chugai previously established an LGR5+ human colorectal cancer (CRC) stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted colorectal CSC markers and that can dynamically switch between proliferative and drug-resistant noncycling states. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, we found that c-Myc expression was substantially decreased in colorectal CSCs. The c-Myc expression alterations were mediated by upregulation of F-box/WD repeat-containing protein 7 (FBXW7), as evidenced through FBXW7-small interfering RNA knockdown experiments that resulted in enhanced cell sensitivity to anticancer agents. Upregulation of FBXW7 following drug treatment was not evident in commercially available cancer cell lines. Colorectal CSCs were induced to differentiation by Matrigel and fetal bovine serum. Differentiated CSCs treated with anticancer agents did not show upregulation of FBXW7 and were more sensitive to irinotecan (CPT-11), highlighting the potential CSC-specific nature of our data. The FBXW7 over-expression was further validated in resected liver metastatic sites in CRC patients after chemotherapy. In conclusion, our study revealed that a CSC-specific FBXW7-regulatory mechanism is strongly associated with resistance to chemotherapeutic agents. Inhibition of FBXW7-upregulation in CSCs following chemotherapy may enhance the response to anticancer agents and represents an attractive strategy for the elimination of colorectal CSCs. Stem Cells 2017;35:2027-2036.


Assuntos
Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Proteína 7 com Repetições F-Box-WD/metabolismo , Células-Tronco Neoplásicas/patologia , Proteólise , Proteínas Proto-Oncogênicas c-myc/metabolismo , Regulação para Cima , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Proteína 7 com Repetições F-Box-WD/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Proteólise/efeitos dos fármacos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Regulação para Cima/efeitos dos fármacos
17.
Int J Clin Oncol ; 22(5): 913-920, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28526907

RESUMO

BACKGROUND: This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC). METHODS: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m2 on day 1 plus capecitabine 800 mg/m2 b.i.d. on days 1-14) every 3 weeks. The primary endpoint was the objective tumor response rate. RESULTS: A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1-70.2%). The median progression-free survival was 9.6 months (95% CI 5.1-11.1 months) and the median overall survival was 23.1 months (95% CI 11.3-36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism. CONCLUSIONS: A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Povo Asiático , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina/administração & dosagem , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Glucuronosiltransferase , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Estudos Prospectivos , Resultado do Tratamento
18.
Langenbecks Arch Surg ; 402(2): 333-341, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28138759

RESUMO

PURPOSE: The aim of this study is to confirm the predictive value of controlling nutritional status (CONUT), as a postoperative prognostic marker for esophageal cancer patients undergoing esophagectomy. METHODS: We retrospectively analyzed 373 patients who underwent three-incision esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and March 2016. The patients were divided into three groups based on the degree of preoperative malnutrition as assessed by CONUT: normal, light malnutrition, and moderate or severe malnutrition. RESULTS: The patients with moderate or severe malnutrition experienced a significantly higher frequency of reoperation (normal or light malnutrition, 6.3%; moderate or severe malnutrition, 18.2%; P = 0.033) and a higher tendency for respiratory morbidities (normal or light malnutrition, 14.0%; moderate or severe malnutrition, 27.3%; P = 0.088). Cox regression analysis identified a significantly poor prognosis, in both overall survival (hazard ratio (HR), 3.56; 95% confidence interval (CI), 1.714-7.390; P < 0.001) and cancer-specific survival (HR, 3.41; 95% CI, 1.790-6.516; P = 0.046). CONCLUSIONS: CONUT is convenient and useful for preoperatively assessing malnutrition and prognosis of esophageal cancer patients who underwent surgery.


Assuntos
Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Desnutrição/etiologia , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Idoso , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
19.
Int J Clin Oncol ; 22(4): 740-748, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28213742

RESUMO

BACKGROUND: Various systemic inflammatory and nutritional scores have been reported to predict postoperative outcomes. This study aimed to investigate the best systemic inflammatory and nutritional scores in colorectal cancer (CRC) patients who underwent potentially curative resection. METHOD: We evaluated 468 consecutive CRC patients in this study. Comparisons of systemic inflammatory and nutritional scores, including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS), were performed using univariate/multivariate analyses for patient survival. RESULTS: The PNI and mGPS, but not the NLR, PLR, and PI, were significantly associated with overall and relapse-free survival. The mGPS, but not the PNI, was strongly correlated with TNM stage (P < 0.001). Cox multivariate analysis showed that both the PNI and mGPS were exclusive independent prognostic factors for both overall and relapse-free survival (P < 0.001). Furthermore, the PNI status predicted patient survival more clearly than the mGPS in combination with TNM stage. CONCLUSIONS: This study suggests that the PNI and mGPS are useful predictive scores in CRC patients who undergo potentially curative resection, especially the PNI in combination with TNM stage. Routine evaluation of the host status using the scores may be useful in CRC treatment.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Linfócitos/patologia , Neutrófilos/patologia , Avaliação Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Prognóstico , Análise de Sobrevida
20.
Int J Clin Oncol ; 22(3): 469-475, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28097441

RESUMO

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to predict the prognosis of various malignant tumors, including esophageal cancer. However, no previous reports have supported the use of the preoperative NLR as an independent prognostic marker focused on superficial (T1) esophageal cancer. The aim of this study was to elucidate the prognostic impact of the preoperative NLR in T1 esophageal cancer. METHODS: This retrospective study recruited 245 consecutive patients with T1 esophageal cancer who underwent subtotal esophagectomy between 2005 and 2016. The relationship between the preoperative NLR and clinicopathological characteristics was analyzed. RESULTS: The preoperative NLR was significantly higher in male patients (p = 0.029), patients with T1b esophageal cancer (p = 0.0274), and patients with venous vessel invasion (p = 0.0082). In the Kaplan-Meier analysis, the elevated preoperative NLR was significantly associated with a poorer disease-free survival (p < 0.0001) and overall survival (p = 0.0004). In the multivariate Cox model, the elevated preoperative NLR was an independent prognostic marker for both disease-free survival (p = 0.0013) and overall survival (p = 0.0027). CONCLUSION: An elevated preoperative NLR predicts poor prognosis in T1 esophageal cancer, suggesting the utility of the NLR as an easily measurable and generally available independent prognostic marker.


Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Linfócitos/patologia , Neutrófilos/patologia , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Esofagectomia , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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