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BACKGROUND/AIM: The aim of the present study was to investigate whether perineural invasion (PNI) was a prognostic index for patients who underwent curative surgery for Dukes' grade B and C rectal cancer. PATIENTS AND METHODS: A total of 645 patients with rectal cancer between January 2000 and December 2011; 363 with Dukes' B or C stages who did not undergo chemoradiotherapy were reviewed. RESULTS: Of 363 patients, 83 (22.9%) were PNI-positive. The 5-year overall survival and disease-specific survival rates were significantly worse for patients with PNI-positive Dukes' B or C disease compared to those with PNI-negative disease. There was no significant difference in the recurrence pattern (hematogenous or lymphatic spread), but patients with PNI-positive disease had a significantly higher rate of recurrence compared to those with PNI-negative disease (p<0.001). CONCLUSION: PNI was a significant prognostic factor in rectal cancer, and the PNI status in primary rectal cancer pathology specimens should be considered for therapy stratification.
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Gastrectomia/métodos , Nervos Periféricos/patologia , Neoplasias Retais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias Retais/patologia , Adulto JovemRESUMO
Intersphincteric resection (ISR) has rapidly increased worldwide including laparoscopic surgery. However, there are some concerns for the definition of ISR, surgical technique, oncological outcome, anal function, and quality of life (QoL). The aim of the present study is to evaluate those issues. A review of this surgical technique was carried out by searching English language literature of the PubMed online database and appropriate articles were identified. With regard to open-ISR, the morbidity rate ranged from 7.5% to 38.3%, with lower mortality rates. Local recurrence rates varied widely from 0% to 22.7%, with a mean follow-up duration of 40-94 months. Disease-free and overall 5-year survival rates were 68-86% and 76-97%, respectively. Those outcomes were equivalent to laparoscopic-ISR. Surgical and oncological outcomes of ISR were generally acceptable. However, accurate evaluation of anal function and QoL was difficult because of a lack of standard assessment of various patient-related factors. The surgical and oncological outcomes after ISR seem to be acceptable. The ISR technique seems to be valid as an alternative to abdominoperineal resection in selected patients with a very low rectal cancer. However, both necessity for ISR and expectations of QoL impairment as a result of functional disorder should be fully discussed with patients before surgery.
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BACKGROUND: This study was designed to evaluate the efficacy and safety of XELOX plus bevacizumab in a Japanese metastatic colorectal cancer population that included elderly patients. METHODS: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated metastatic colorectal cancer, presence of measurable lesions, age ≥ 20 years; Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELOX (130 mg/m(2) oxaliplatin on day 1 plus 1,000 mg/m(2) capecitabine b.i.d. on days 1-14) every 3 weeks. The primary endpoint was confirmed objective response rate. RESULTS: The study included 47 patients (male/female 30/17; median age 69 years; age range 38-81 years with 10 patients ≥ 75 years; PS 0/1/2, 40/5/2) enrolled between May 2010 and March 2011. Responses were assessed in 46 eligible patients. The objective response rate was 52.2 % (95 % confidence interval [CI] 37.0-67.1). The median progression-free survival and overall survival were 10.0 months (95 % CI 7.8-12.3) and 34.6 months (95 % CI 19.9-not estimable), respectively. Frequently encountered grade 3 and 4 adverse events in this study were aspartate aminotransferase elevation (23.4 %), alanine aminotransferase elevation (21.3 %), anorexia (12.8 %), neutropenia (10.6 %), fatigue (8.5 %) and anemia (6.4 %). Grade 3 or 4 peripheral neuropathy was not observed. CONCLUSION: First-line treatment with XELOX plus bevacizumab showed a promising response rate and an acceptable tolerability profile in the clinical practice of Japanese metastatic colorectal cancer patients that included elderly patients. REGISTRY: UMIN-CTR, ID number: UMIN000003915, URL:https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004706&language=E.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Anorexia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Neoplasias Colorretais/patologia , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Fadiga/induzido quimicamente , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Oxaloacetatos , Estudos ProspectivosRESUMO
Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression.
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Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/genética , Di-Hidrouracila Desidrogenase (NADP)/genética , Endonucleases/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/genética , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Hepatectomia/métodos , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Several reports showed that neoplastic spindle cells (NSCs) may be strongly involved in the invasion, metastasis, and poor prognosis, as well as in epithelial-mesenchymal transition (EMT). It has not yet been investigated that NSCs relate to the recurrence and prognosis in various cancers. Furthermore, NSCs participate in EMT in pancreatic cancer (PC) too. We clinicopathologically investigated the association between NSCs and the recurrence, prognosis, and EMT in PC. METHODS: We studied 68 PC patients. Cancer cells with a spindle or oval shape that do not exhibit luminal structures were defined as NSCs. We graded NSCs regarding to an area of NSCs at hematoxylin and eosin stain (NSC grade) and examined the participation in NSCs and EMT by immunohistostaining of snail antibody and E-cadherin antibody. RESULTS: In multivariate analysis, NSC grade was an independent risk factor for disease-free survival and overall survival. This was independent of TNM stage and histological grade. Neoplastic spindle cells were related to EMT pattern in immunohistostaining significantly. CONCLUSIONS: Neoplastic spindle cell grade significantly related to the recurrence and prognosis of PC. The NSC grade assessment can be not only performed inexpensively and conveniently, but also used to guide future individualized therapeutic approaches. Furthermore, NSCs were found to relate to EMT profoundly.
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Carcinoma Ductal Pancreático/patologia , Forma Celular , Transição Epitelial-Mesenquimal , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Biomarcadores Tumorais/análise , Caderinas/análise , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Transcrição da Família Snail , Fatores de Tempo , Fatores de Transcrição/análise , Resultado do TratamentoRESUMO
BACKGROUND: Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10), phenylacetylglutamine plus phenylacetylisoglutamine (A10-I), and phenylacetylglutamine plus phenylacetate (AS2-1). This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver. METHODS: Sixty-five patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998- 2004 in Kurume University Hospital. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1) plus HAI (AN arm) or HAI alone (control arm) based on the number of metastases and presence/ absence of extra-hepatic metastasis at the time of surgery. Primary endpoint was cancer-specific survival (CSS); secondary endpoints were relapse-free survival (RFS), status and extent of recurrence, salvage surgery (rate) and toxicity. FINDINGS: Overall survival was not statistically improved (p=0.105) in the AN arm (n=32). RFS was not significant (p=0.343). Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n=33) with a median survival time 67 months (95%CI 43-not calculated) versus 39 months (95%CI 28-47) (p=0.037) and 5 year CSS rate 60% versus 32% respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumours in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the stomach and phlebitis. No serious toxicity, including bone marrow suppression, liver or renal dysfunction, were found in the AN arm. INTERPRETATION: Antineoplastons (A10 Injection and AS2-1) might be useful as adjunctive therapy in addition to HAI after hepatectomy in colorectal metastases to the liver. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov UMIN000012099.
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Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzenoacetamidas/administração & dosagem , Benzenoacetamidas/uso terapêutico , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/cirurgia , Combinação de Medicamentos , Fluoruracila/uso terapêutico , Glutamina/administração & dosagem , Glutamina/análogos & derivados , Glutamina/uso terapêutico , Hepatectomia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Fenilacetatos/administração & dosagem , Fenilacetatos/uso terapêutico , Piperidonas/administração & dosagem , Piperidonas/uso terapêutico , Análise de Sobrevida , Resultado do TratamentoRESUMO
The aim of this study was to elucidate whether fecoflowmetry (FFM) could evaluate more detailed evacuative function than anorectal manometry by comparing between FFM or anorectal manometric findings and the clinical questionnaires and the types of surgical procedure in the patients who received anal-preserving surgery. Fifty-three patients who underwent anal-preserving surgery for low rectal cancer were enrolled. The relationships between FFM or the manometric findings and the clinical questionnaires and the types of procedure of anal-preserving surgery were evaluated. There were significant differences between FFM markers and the clinical questionnaire and the types of the surgical procedure, whereas no significant relationship was observed between the manometric findings and the clinical questionnaire and the types of the surgical procedure. FFM might be feasible and useful for the objective assessment of evacuative function and may be superior to manometry for patients undergoing anal-preserving surgery.
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Canal Anal/fisiopatologia , Defecação/fisiologia , Incontinência Fecal/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Neoplasias Retais/cirurgia , Reto/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/cirurgia , Incontinência Fecal/etiologia , Incontinência Fecal/fisiopatologia , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Período Pós-Operatório , Neoplasias Retais/fisiopatologia , Reto/cirurgia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Malignant lymphomas of the breast are rare and primary breast lymphoma comprises <0.5 % of breast malignancies, within which T-cell lymphomas are an even rarer subset. We report a case of primary breast peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). Histology of the biopsied specimen revealed CD2(+), CD3(+), CD4(+), CD5(-), CD7(+), CD8(-), CD20(-), CD25(-), CD30(+), CD56(-), bcl-2(-), EBV-ISH(-), TIA-I(-), and ATLA negative. The patient was treated with six cycles of the CHOP regimen and died 17 months after the diagnosis was made, despite complete remission after conventional chemotherapy. To our knowledge, only 18 cases of primary peripheral T-cell lymphoma of the breast and just one previous case of primary PTCL-NOS of the breast have been reported in Japan.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamento farmacológico , Idoso , Antígenos CD/análise , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Diagnóstico por Imagem , Doxorrubicina/administração & dosagem , Evolução Fatal , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Células T Periférico/patologia , Prednisolona/administração & dosagem , Indução de Remissão , Vincristina/administração & dosagemRESUMO
BACKGROUND: We investigated the efficacy and safety of metronomic chemotherapy with combined irinotecan and tegafur-gimeracil-oteracil potassium (TS-1) in patients with metastatic and recurrent breast cancer (MRBC), and the association between irinotecan metabolizing enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms and adverse events. METHODS: The study group comprised 40 patients aged 35-79 years. Irinotecan (60 mg/m(2) in 5 % dextrose) was administered by 120-min infusion on days 1, 8, and 15 every 4 weeks. TS-1 (prescribed in a standard quantity) was administered at 80 mg/m(2)/day orally on days 3-7, 10-14, and 17-21 every 4 weeks. RESULTS: Tumor response data were available for 34 patients. Median follow-up was 12 months (range 1-45 months). Response rate was 47 % (one complete and 15 partial responses). Stable disease was observed in 17 patients (50 %). One patient had disease progression (3 %). Median progression-free survival was 14 months [95 % confidence interval (CI), 10-26]. Median overall survival was 26 months (95 % CI not calculable owing to sample size), and 79.3 % of patients survived for 1 year. The most common grade 3 or 4 adverse events were neutropenia (15 %), leukopenia (12.5 %), diarrhea (7.5 %), and anemia (2.5 %). All other adverse events were grade 1 or 2. Treatment-related toxicity was generally modest and manageable. No significant correlation was observed between UGT1A1 polymorphisms and hematological or non-hematological toxicities. CONCLUSIONS: Metronomic chemotherapy with combined irinotecan and TS-1 was effective in MRBC patients. Adverse effects were mild and the regimen was safely administered without identifying UGT1A1 polymorphisms.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Administração Metronômica , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Combinação de Medicamentos , Feminino , Glucuronosiltransferase/genética , Humanos , Irinotecano , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Ácido Oxônico/administração & dosagem , Polimorfismo Genético , Piridinas/administração & dosagem , Análise de Sobrevida , Tegafur/administração & dosagem , Resultado do TratamentoRESUMO
We report the case of a 60-year-old male patient who was diagnosed with metastasis from primary lung cancer to the breast. The patient presented with a mass in the right breast. Mammography, ultrasound, and magnetic-resonance imaging each suggested primary breast cancer. A core-needle biopsy of the right breast mass indicated poorly differentiated adenocarcinoma. A basic chest X-ray showed a shadow in the left upper lung. Thoraco-abdominal computed tomography revealed a mass with a diameter of 90 mm in the left superior region, the shape of which was indicative of primary lung cancer. A lung biopsy confirmed poorly differentiated adenocarcinoma. We diagnosed primary lung cancer with metastases to the bone, brain and right breast (cT2N3M1, stage IV) by imaging and histopathology. He was administered carboplatin (area under the curve 6 mg / ml) and paclitaxel (200 mg / m(2)) tri-weekly, and underwent gamma-knife treatment for the brain metastasis. The treatments reduced the primary tumor and the metastases. However, after completion of the fifth treatment cycle, he developed disseminated intravascular coagulation from septic shock, and died on the eleventh day after completing the fifth cycle of treatment. Although metastasis to the mammary gland is uncommon, especially among males, metastasis to the mammary gland should be considered when a mammary mass does not exhibit the typical characteristics of breast cancer. A correct diagnosis of metastasis to the mammary gland from lung cancer makes it possible to select the most appropriate treatment method.
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Adenocarcinoma/secundário , Neoplasias da Mama Masculina/secundário , Neoplasias Pulmonares/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama Masculina/tratamento farmacológico , Evolução Fatal , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Mamografia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: In patients with strangulation ileus, the severity of bowel ischemia is unpredictable before surgery. To consider a grading scale of anoxic damage, we evaluated the pathological findings and investigated predictive factors for bowel gangrene. METHODS: We assessed 49 patients with strangulation ileus who underwent a laparotomy between January 2004 and November 2012. Laboratory tests and the contrast computed tomography (CT) were evaluated before surgery. According to the degree of mucosal degeneration, we classified anoxic damages into the following 3 grades. Ggrade 1 shows mild mucosal degeneration with extended subepithelial space. Grade 2 shows moderate degeneration and mucosal deciduation with residual mucosa on the muscularis mucosae. Grade 3 shows severe degeneration and mucosal digestion with disintegration of lamina propria. RESULTS: Resected bowel specimens were obtained from the 36 patients with severe ischemia, while the remaining 13 patients avoided bowel resection. The mucosal injury showed grade 1 in 11 cases, grade 2 in 10 cases, and grade 3 in 15 cases. The patients were divided into two groups. One group included grade 1 and non-resected patients (n = 24) while the other included grades 2 and 3 (n = 25). When comparing the clinical findings for these groups, elevated creatine kinase (P = 0.017), a low base excess (P = 0.021), and decreased bowel enhancement on the contrast CT (P = 0.001) were associated with severe mucosal injury. CONCLUSION: In strangulation ileus, anoxic mucosal injury progresses gradually after rapid spreading of bowel congestion. Before surgical intervention, creatine kinase, base excess, and bowel enhancement on the contrast CT could indicate the severity of anoxic damage. These biomarkers could be the predictor for bowel resection before surgery.
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Doenças do Colo/complicações , Íleus/complicações , Mucosa Intestinal/irrigação sanguínea , Obstrução Intestinal/complicações , Isquemia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Doenças do Colo/diagnóstico , Doenças do Colo/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Íleus/diagnóstico , Íleus/cirurgia , Mucosa Intestinal/patologia , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/cirurgia , Isquemia/etiologia , Laparotomia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.
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Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Terapia de Alvo Molecular , Neoplasias Gástricas/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Desenho de Fármacos , Humanos , Técnicas de Diagnóstico Molecular , Seleção de Pacientes , Valor Preditivo dos Testes , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: It has been hypothesized that minichromosome maintenance (MCM) proteins, which are replicative control factors, can be used to detect tumor proliferation. The aim of the present study was to investigate the expression of MCM in colorectal cancer tissues and correlate it to clinical outcomes. PATIENTS AND METHODS: The study included 145 patients with colorectal cancer who underwent curative surgery, from January 2002 until December 2004, at the Kurume University Hospital in Fukuoka, Japan. The median follow-up duration was 87 months. The expression of MCM7 in tissues was studied by immuno-histochemical staining. The labeling index (LI) of MCM7 was calculated by dividing the number of positively-stained cells by the total number of cells counted. We divided samples into two groups: positive (MCM7 LI 76% or higher) and negative (MCM7 LI less than 76%). RESULTS: In patients with Dukes A and B, there were no significant differences in either overall survival (OS) or recurrence-free survival (RFS) between patents with MCM7-positive and those with MCM7-negative disease. On the other hand, in patients with Dukes C, there was significantly worse OS and RFS for patients with MCM7-positive compared to those with MCM7-negative disease. CONCLUSION: We found that the expression of MCM7 is an independent risk factor for RFS in patients with Dukes C colorectal cancer. Further studies are required to investigate the validity of MCM7 protein expression for its potential clinical use in colorectal cancer therapy and prognosis.
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Neoplasias Colorretais/etiologia , Componente 7 do Complexo de Manutenção de Minicromossomo/fisiologia , Recidiva Local de Neoplasia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
BACKGROUND: Pelvic sidewall dissection (PSD) has the potential to decrease local recurrence so that PSD may be an effective strategy for lower rectal cancer. Therefore, it is important to investigate the validity of PSD for its potential clinical use in lower rectal cancer therapy and prognosis. PATIENTS AND METHODS: The present study included all 994 patients with rectal cancer who underwent curative surgery from January 1975 until December 2004 at the Kurume University Hospital in Fukuoka. The patients were analyzed to determine whether lateral lymph node (LLN) metastasis was correlated with clinicopathological factors, and in the overall study population, 5-year disease-free survival (DFS), and the 5-years overall survival (OS) were analyzed. RESULTS: In patients with stage 3a cancer there was no significant difference in DFS between those with and without PSD. On the other hand, in patients with stage 3b DFS was significantly worse with PSD than without PSD. We analyzed the DFS and OS according to the number of lymph nodes with LLN-positive metastasis. Those with fewer than three positive lymph nodes had a significantly better DFS and OS compared to those with three or more. Moreover, those with only ore region of positive lymph node had a significantly better DFS and OS compared to those with two or more regions. CONCLUSION: These results demonstrate that PSD was of benefit for prognosis for patients with fewer than three positive lymph nodes, those limited to within only one region and LLN metastasis only.
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Excisão de Linfonodo , Neoplasias Retais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Neoplasias Retais/mortalidade , Neoplasias Retais/patologiaRESUMO
BACKGROUND AND OBJECTIVES: Identification of suitable predictors of local recurrence (LR) in patients with rectal cancer would be of clinical benefit. The aim of this study was to identify histopathological factors that could predict LR. METHODS: A total of 796 stage II/III patients with pT3 and pT4 rectal cancer who did not undergo preoperative chemoradiation were enrolled. LR was defined as intra-pelvic recurrence only. Histopathological factors related to LR were investigated. RESULTS: LR was found in 25 patients (6.1%) with stage II and 54 patients (13.9%) with stage IIIB/IIIC. In patients with stage II, distance of mesorectal extension (DME) >4 mm (P = 0.011) and positive venous invasion (P = 0.035) were independent factors that predicted LR. In patients with stage IIIB/IIIC, circumferential resection margin (CRM) ≤1 mm (P = 0.003) and positive lymphatic invasion (P = 0.006) were independent factors. The cumulative 5-year LR rate was higher (11.9%) in patients with a combination of DME > 4 mm and/or positive venous invasion for stage II (P < 0.001), and was also higher in patients with a combination of CRM≤1 mm and/or positive lymphatic invasion for stage IIIB and IIIC (22.2%; P < 0.002, and 34.3%; P < 0.006, respectively). CONCLUSIONS: Important histopathological predictors for LR in patients with pT3 and pT4 rectal cancer were different at each stage.
Assuntos
Adenocarcinoma/patologia , Recidiva Local de Neoplasia , Neoplasias Retais/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Fatores de RiscoRESUMO
Intersphincteric resection (ISR) has recently been performed for very low rectal cancer, whereas abdominoperineal resection (APR) is typically reserved for cancers extremely close to the anal verge and/or when the depth of tumor invasion is suspected to involve the intersphincteric space. This is because impairment of anal function is considered unavoidable if the external sphincter (ES) is excised. We describe our technique of ISR with ES resection and discuss its outcomes. This surgical technique may offer major clinical advantages to selected patients and should be considered as an alternative to APR, although careful consideration of anal function is required.
Assuntos
Adenocarcinoma/cirurgia , Canal Anal/cirurgia , Neoplasias do Ânus/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Tratamentos com Preservação do Órgão/métodos , Satisfação do Paciente , Recuperação de Função Fisiológica/fisiologia , Neoplasias Retais/cirurgia , Canal Anal/fisiologia , HumanosRESUMO
Poor nutrition and weight loss are important factors contributing to poor quality of life (QOL) after gastrectomy in patients with gastric cancer. Ghrelin is a hormone produced by the stomach that, plays a role in appetite increase and fat storage. The present study aims to clarify the location of ghrelin mRNA in the stomach, changes in blood ghrelin concentrations after gastrectomy and whether or not they are associated with the reconstruction method in patients with gastric cancer. We collected seven normal mucosa samples from different parts of six totally resected stomachs with gastric cancer. We extracted RNA from the normal mucosa, synthesized cDNA from total RNA (1 µg), and then quantified ghrelin mRNA using quantitative real-time polymerase chain reaction (Q-PCR). Ghrelin blood concentrations were measured using enzyme-linked immunosorbent assay (ELISA) kits in 74 patients with gastric cancer (total gastrectomy (TG), n=23; distal gastrectomy (DG), n=30; proximal gastrectomy (PG), n=11; pylorus preserving gastrectomy (PPG), n=10). In order, the ghrelin gene was expressed most frequently in the gastric body, followed by the fornix, cardia, antrum and pylorus ring. Blood ghrelin concentrations after surgery similarly changed in all groups. The average blood ghrelin concentrations were significantly higher in the DG and PPG groups than in the TG group on postoperative days (POD) 1, 7, 30, 90 and 180. However, blood ghrelin concentrations did not significantly differ between the DG and TG groups on POD 270 and 360. Cells that produce ghrelin are supposed to be located mostly in the fundic gland of the stomach. We speculate that the production of ghrelin from other organs increases from around nine months after total gastrectomy. Therefore, evaluating the nutritional status and the weight of patients at nine months after total gastrectomy is important to help these patients improve their QOL.
Assuntos
Biomarcadores Tumorais/genética , Grelina/genética , Neoplasias Gástricas/genética , Estômago/química , Adulto , Idoso , Biomarcadores Tumorais/sangue , Índice de Massa Corporal , Ensaio de Imunoadsorção Enzimática , Feminino , Gastrectomia/métodos , Mucosa Gástrica/química , Grelina/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
Using a rat laparotomy stress model, we conducted a comparative analysis of postoperative organ metastasis after administration of ulinastatin (UTI) or methylprednisolone (MP), which have an inhibitory effect on cytokine production. The subjects were classified into 4 groups: 1) minimal laparotomy group (C group), 2) major laparotomy group (L group), 3) preoperative MP intravenous administration + major laparotomy group (MP group), and 4) preoperative UTI intravenous administration + major laparotomy group (UTI group). Either MP or UTI was administered intravenously before surgery, and RI-labeled cells were injected into the portal vein immediately after laparotomy to collect tissue specimens in order to measure radiation dosage. Then, the concentrations of serum IL-2 and IL-6, liver interleukin 1 beta (IL-1ß) and interleukin 10 (IL-10), and liver E-selectin were measured. In addition natural killer cell, (NK cell) activation and neoplastic nodules on the liver surface at 3 weeks after surgery were also measured. The adhesion rate of malignant cells to the liver was higher in the L group than in the C group, higher in the MP group than the L group, and lower overall in the UTI group. The concentration of IL-1ß and IL-6 were decreased in the MP and UTI groups compared to the L group. IL-2 was decreased significantly in the MP group compared with the C and L groups. E-selectin expression level decreased in the UTI group compared with the L group. NK cell activation decreased in the MP group compared with the C group and L group, but no differences were observed between the UTI and L groups. The number of tumor nodules on the surface of the liver increased in the MP group compared with the L group, and decreased in the UTI group compared with the L group. Postoperative alleviation of invasive reaction was suggested in both the MP and UTI groups. However, preoperative administration of MP increased metastasis while that of UTI inhibited metastasis. MP was considered to have decreased anti-tumor immunocompetence and promoted metastasis, while UTI was considered to have inhibited the expression of adhesive molecules and decreased metastasis.
Assuntos
Antineoplásicos/farmacologia , Glucocorticoides/toxicidade , Glicoproteínas/farmacologia , Laparotomia/efeitos adversos , Neoplasias Hepáticas Experimentais/prevenção & controle , Neoplasias Hepáticas Experimentais/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/prevenção & controle , Metilprednisolona/toxicidade , Administração Intravenosa , Animais , Antineoplásicos/administração & dosagem , Ascite/patologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/sangue , Esquema de Medicação , Glucocorticoides/administração & dosagem , Glicoproteínas/administração & dosagem , Hospedeiro Imunocomprometido , Mediadores da Inflamação/sangue , Neoplasias Hepáticas/imunologia , Masculino , Metilprednisolona/administração & dosagem , Transplante de Neoplasias , Cuidados Pré-Operatórios , Ratos , Fatores de TempoRESUMO
BACKGROUND: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis. METHODS: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum. RESULTS: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection. CONCLUSIONS: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.
Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Peritoneais/patologia , Adenocarcinoma/patologia , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Japão , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Peritoneais/classificação , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The histogenesis of the pattern of cancer spread along Auerbach's plexus (myenteric spread: MS) remains unclear and its prognostic value in colorectal cancer (CRC) has not been thoroughly investigated. METHODS: Pathology slides of 2845 pT2/pT3/pT4 CRCs stained with hematoxylin-eosin (H&E) were reviewed at 10 institutions. MS was classified into 2 groups depending on whether it was accompanied by the finding of perineural invasion (PN) within the lesion. In addition, immunohistochemical staining (D2-40, S100, CD56, synaptophysin) was performed for serially sectioned specimens from 50 CRCs diagnosed as having PN-negative MS. RESULTS: MS was observed in 504 patients (17.7 %); 360 patients were classified as having PN-positive MS and 144 as having PN-negative MS. The 5-year disease-free survival rate of patients with MS was lower than that of patients without MS (63.3 vs 82.7 %, P < 0.0001); however, there was no significant difference in survival outcome according to the presence or absence of intralesion PN in MS. Multivariate analysis showed that the prognostic impact of MS was independent of conventional prognosticators including T and N stages, vascular invasion and extramural PN. In all the tumors having PN-negative MS, remnants of neural tissue were identified within or around cancer nests located at the leading edge of MS. CONCLUSIONS: MS is an important prognostic factor for CRC. This feature is the result of cancer development with replacement of Auerbach's plexus and can be classified as intramural PN. The clinical significance of "Pn1" in the UICC/AJCC TNM classification could be enhanced by individual assessment both intramurally and extramurally.