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1.
BMC Cancer ; 15: 384, 2015 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-25956750

RESUMO

BACKGROUND: The aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC). METHODS: Patients were assigned to oxaliplatin, leucovorin and 5-FU for 12 cycles (group A, FOLFOX6) or oxaliplatin and capecitabine for eight cycles (group B, CAPOX). Primary endpoint was disease-free survival (DFS). Tumors were classified as mismatch repair proficient (pMMR) or deficient (dMMR) according to MLH1, PMS2, MSH2 and MSH6 protein expression. KRAS exon two and BRAF V600E mutational status were also assessed. RESULTS: Between 2005 and 2008, 441 patients were enrolled, with 408 patients being eligible. After a median follow-up of 74.7 months, 3-year DFS was 79.8 % (95 % CI 76.5-83.4) in the FOLFOX group and 79.5 % (95 % CI 75.9-83.1) in the CAPOX group (p = 0.78). Three-year OS was 87.2 % (95 % CI 84.1-91.1) in the FOLFOX and 86.9 % (95 % CI 83.4-89.9) in the CAPOX group (p = 0.84). Among 306 available tumors, 11.0 % were dMMR, 34.0 % KRAS mutant and 4.9 % BRAF mutant. Multivariate analysis showed that primary site in the left colon, earlier TNM stage and the presence of anemia at diagnosis were associated with better DFS and overall survival (OS), while grade one-two tumors were associated with better OS. Finally, a statistically significant interaction was detected between the primary site and MMR status (p = 0.010), while KRAS mutated tumors were associated with shorter DFS. However, the sample was too small for safe conclusions. CONCLUSIONS: No significant differences were observed in the efficacy of FOLFOX versus CAPOX as adjuvant treatment in high-risk stage II or stage III CRC patients, but definitive conclusions cannot be drawn because of the small sample size. TRIAL REGISTRATION: ANZCTR 12610000509066 . Date of Registration: June 21, 2010.


Assuntos
Capecitabina/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Compostos Organoplatínicos/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Instabilidade de Microssatélites/efeitos dos fármacos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/genética
2.
J Surg Res ; 197(2): 291-300, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25976855

RESUMO

BACKGROUND: Peritoneal adhesions, organized as fibrous bands after abdominal surgery, are related with considerable morbidity and repeated hospitalization. Phospholipids, natural constituents of the peritoneal fluid, seem to display excellent antiadhesive properties. The aim of this study was to investigate whether intraperitoneal application of phospholipids is capable of reducing postoperative adhesions and the possible underlying mechanisms. MATERIALS AND METHODS: Twenty male Wistar rats were subjected to a midline laparotomy and a standard peritoneal and cecum abrasion trauma. Before laparotomy closure, a bolus of 3 mL of phospholipids (12 mg/mL) or NaCl (placebo) was given intraperitoneally. Seven days later, the quality and the quantity of adhesions, as well as serum proinflammatory and/or profibrotic mediators, were blindly assessed. Human colonic subepithelial myofibroblasts were isolated from normal controls and cultured with transforming growth factor-ß1 (TGFß1, 5 ng/mL) in the presence of phospholipids (30-300 µg/mL). Collagen production in culture supernatants and migratory activity of myofibroblasts were also assessed. RESULTS: Phospholipids reduced intra-abdominal adhesions (P < 0.001), with respect to their intensity and area, and serum levels of cytokines (interleukin 1ß, interleukin 6, platelet-derived growth factor-1, and TGFß1) compared with placebo-treated rats. Stimulation of myofibroblasts with TGFß1 significantly increased (P < 0.001) the basic collagen production. The presence of phospholipids significantly reduced (P < 0.001) both the TGFß1 induced and the basic collagen production. Using a wound healing assay, phospholipids were found to reduce the basic and the TGFß1-induced migration of myofibroblasts in a concentration-dependent manner. CONCLUSIONS: Intraperitoneal phospholipids might be involved in the prevention of postoperative adhesions formation via the reduction of proinflammatory and/or profibrotic mediators and by inhibiting fibrogenic properties of mesenchymal cells.


Assuntos
Miofibroblastos/efeitos dos fármacos , Fosfolipídeos/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Animais , Biomarcadores/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Humanos , Injeções Intraperitoneais , Laparotomia , Masculino , Miofibroblastos/metabolismo , Peritônio/cirurgia , Fosfolipídeos/farmacologia , Complicações Pós-Operatórias/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Aderências Teciduais/etiologia , Aderências Teciduais/metabolismo
3.
World J Surg ; 39(11): 2776-83, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25894405

RESUMO

BACKGROUND: Heterogeneous results of published studies led to conduct a randomized clinical trial to assess the efficacy of a new formulation of four probiotics as prophylaxis for complications after colorectal surgery. METHODS: A double-blind, placebo-controlled randomized study was conducted enrolling patients undergoing colorectal surgery for cancer. Capsules of placebo or of a formulation containing Lactobacillus acidophilus, L. p lantarum, Bifidobacterium lactis and Saccharomyces boulardii were administered starting one day before operation and continuing for another 15 days postoperatively. Patients were followed up for 30 days with the development of postoperative complications as the primary outcome. Gene expression and serum levels of cytokines were measured on postoperative day 4 ( www.clinicaltrials.gov NCT02313519). RESULTS: The study was prematurely stopped after enrolment due to efficacy in the primary outcome. Administration of probiotics significantly decreased the rate of all postoperative major complication (28.6 vs. 48.8 % of the placebo arm, p 0.010, odds ratio 0.42). Major benefit was found in the reduction of the rate of postoperative pneumonia (2.4 vs. 11.3 %, p 0.029), of surgical site infections (7.1 vs. 20.0 %, p 0.020) and of anastomotic leakage (1.2 vs. 8.8 %, p 0.031). The time until hospital discharge was shortened as well. Gene expression of SOCS3 was positively related with gene expression of TNF and of circulating IL-6 in the probiotic group but not in the placebo group. CONCLUSIONS: The studied probiotic formulation significantly decreased the risk of postoperative complications, namely mechanical ventilation, infections and anastomotic leakage. Modulation of the gene expression of SOCS3 is one suggested mechanism ( www.clinicaltrials.gov NCT02313519).


Assuntos
Fístula Anastomótica/prevenção & controle , Neoplasias Colorretais/cirurgia , Pneumonia/prevenção & controle , Probióticos/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Bifidobacterium , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Feminino , Expressão Gênica , Humanos , Interleucina-6/sangue , Lactobacillus acidophilus , Lactobacillus plantarum , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Saccharomyces , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Fator de Necrose Tumoral alfa/genética
4.
BMC Cancer ; 14: 111, 2014 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-24555920

RESUMO

BACKGROUND: Bevacizumab, an antibody neutralizing Vascular Endothelial Growth Factor (VEGF), is licensed for the management of patients with advanced colon cancer. However, tumor biomarkers identifying the molecular tumor subsets most amenable to angiogenesis modulation are lacking. METHODS: We profiled expession of 24526 genes by means of whole genome 24 K DASL (c-DNA-mediated, Annealing, Selection and Ligation) arrays, (Illumina, CA) in 16 bevacizumab-treated patients with advanced colon cancer (Test set). Genes with correlation to 8-month Progression-free status were studied by means of qPCR in two independent colon cancer cohorts: 49 patients treated with bevacizumab + chemotherapy (Bevacizumab qPCR set) and 72 patients treated with chemotherapy only (Control qPCR set). Endpoints were best tumor response before metastasectomy (ORR) and progression-free survival (PFS). RESULTS: Five genes were significantly correlated to 8-month progression-free status in the Test set: overexpression of KLF12 and downregulation of AGR2, ALDH6A1, MCM5, TFF2. In the two independent datasets, irinotecan- or oxaliplatin-based chemotherapy was administered as first-line treatment and metastasectomies were subsequently applied in 8-14% of patients. No prognostically significant gene classifier encompassing all five genes could be validated in the Bevacizumab or Control qPCR sets. The complex gene expression profile of all-low tumor (ALDH6A1 + TFF2 + MCM5) was strongly associated with ORR in the Bevacizumab qPCR set (ORR 85.7%, p = 0.007), but not in the Control set (ORR 36.4%, p = 0.747). The Odds Ratio for response for the all-low tumor (ALDH6A1 + TFF2 + MCM5) profile versus any other ALDH6A1 + TFF2 + MCM5 profile was 15 (p = 0.018) in the Bevacizumab qPCR set but only 0.72 (p = 0.63) in the Control set. The tumor expression profile of (KLF12-high + TFF2-low) was significantly associated with PFS only in the Bevacizumab qPCR set: bevacizumab-treated patients with (KLF12-high + TFF2-low) tumors had superior PFS (median 14 months, 95% CI 2-21) compared to patients with any other (KLF12 + TFF2) expression profile (median PFS 7 months, 95% CI 5-10, p = 0.021). The Hazard Ratio for disease progression for (KLF12-high + TFF2-low) versus any other KLF12 + TFF2 expression profile was 2.92 (p = 0.03) in the Validation and 1.29 (p = 0.39) in the Control set. CONCLUSIONS: Our «three-stage¼ hypothesis-generating study failed to validate the prognostic significance of a five-gene classifier in mCRC patients. Exploratory analyses suggest two gene signatures that are potentially associated with bevazicumab benefit in patients with advanced colon cancer.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Oncologia/métodos , Pesquisa Translacional Biomédica/métodos , Adulto , Idoso , Bevacizumab , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/epidemiologia , Feminino , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Resultado do Tratamento , Fator Trefoil-2 , Adulto Jovem
5.
Surg Endosc ; 26(2): 330-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21898023

RESUMO

BACKGROUND: Surgical interventions activate a cascade of reactions that result in an aseptic inflammatory reaction. This inflammatory response initiates the organism's innate immunity. Laparoscopic surgery reduces the trauma, and patients benefit from diminished surgical trauma and maintained immune function. Cytokine levels and C-reactive protein (CRP) are related to the magnitude of surgical trauma and surgical stress. Toll-like receptors (TLRs) 2 and 4 are the first sensor-recognition receptors of the invading pathogens for the innate immune response. This study aimed to compare the inflammatory response and then the stress response during laparoscopic and open colectomy for cancer by calculating TLR-2 and TLR-4 as the first sensor-recognition receptors together with interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity CRP (hsCRP). METHODS: A total 40 patients with colorectal cancer were randomized in two groups: group A (open colectomy, n = 20) and group B (laparoscopic colectomy, n = 20). An epidural catheter was placed in all patients 1 h preoperatively. Rupivocaine was administered perioperatively and 48 h postoperatively. Blood samples were taken for calculation of IL-6, TNF-α, hsCRP, TLR-2, and TLR-4 preoperatively and 5 min after deflation of pneumoperitoneum (group B) or 5 min after division of the colon (group A), then 6 and 24 h postoperatively. RESULTS: The mean operative time was 115 for group A and 142 min for group B. The mean blood loss was respectively 240 and 105 ml (P < 0.001), and the mean hospital stay was respectively 8 and 5 days (P < 0.05). The IL-6 level was significant higher in group A than in group B at 6 and 24 h postoperatively (P < 0.0001), and the hsCRP level was significant higher in group A than in group B at 24 h postoperatively (P < 0.001). The TNF-α values did not differ between the two groups. The TLR-2 level was significantly higher in group A than in group B at 5 min (P = 0.013) and 24 h (P = 0.007) postoperatively. The TLR-4 level was significant higher in group A than in group B at 5 min postoperatively (P = 0.03). CONCLUSION: The inflammatory response and the resultant stress response are significantly less during laparoscopic colectomy than during open colectomy for colorectal cancer. This is an obvious short-term clinical benefit for the patient, providing tinder for further study to investigate the long-term results of laparoscopic colectomy versus open colectomy for colorectal cancer.


Assuntos
Colectomia/métodos , Neoplasias Colorretais/cirurgia , Laparoscopia/métodos , Receptores Toll-Like/metabolismo , Idoso , Proteína C-Reativa/metabolismo , Colite/imunologia , Neoplasias Colorretais/imunologia , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Inata , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Fator de Necrose Tumoral alfa/metabolismo
6.
BMC Med ; 9: 10, 2011 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-21281463

RESUMO

BACKGROUND: Colon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer. METHODS: The study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (i.v.), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 i.v. bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years. RESULTS: The probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms. CONCLUSIONS: Irinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12610000148077.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Grécia , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento , Adulto Jovem
7.
World J Surg ; 35(8): 1911-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21567262

RESUMO

BACKGROUND: Surgical procedures are related to the activation of the inflammatory reaction. This is called surgical stress. It is believed that diminished surgical trauma reduces surgical stress. The laparoscopic approach reduces trauma, but the systemic immune responses are still invariably activated. Cytokines and C-reactive protein (CRP) are the main markers in the study of inflammatory or stress response. α-Defensins play an important role in host defense, acting early in phagocytosis. α-Defensins, as early markers-earlier than cytokines-of the inflammatory response, have been used, together with high-sensitivity CRP (hs-CRP) and interleukin-6 (IL-6), to determine the inflammatory response in laparoscopic and open colectomy for cancer. MATERIALS AND METHODS: A total of 40 patients with colorectal cancer were randomized to two groups: group A (n = 20), open colectomy; group B (n = 20), laparoscopic colectomy. One hour preoperatively an epidural catheter was placed in all patients and rupivacaine was administered perioperatively and again 48 h postoperatively. Blood samples were taken for calculating α-defensins, IL-6, and hs-CRP levels preoperatively, 5 min after division of the colon (group A), or 5 min after deflation of pneumoperitoneum (group B), 6 h and 24 h postoperatively. RESULTS: The mean operative time was 115 min for group A and 142 min for group B (p < 0.05). The mean blood loss was 240 ml and 105 ml, respectively (p < 0.001). The mean hospital stay was 8 days and 5 days, respectively (p < 0.05). α-Defensin levels were statistically significantly lower in group B than in group A, 5 min and 24 h postoperatively (p < 0.002 and p < 0.007, respectively). The IL-6 levels were statistically significantly lower in group B than in group A, 6 h and 24 h postoperatively (p < 0.0001 at both time intervals), whereas the levels of hs-CRP were significantly lower in group B than in group A 24 h postoperatively (p < 0.001). CONCLUSIONS: The present study confirms the results of previous studies, that the inflammatory immune response and surgical stress are significantly less after laparoscopic colectomy versus open colectomy for colorectal cancer. More investigation is needed to study if surgical stress has any influence on survival of these patients.


Assuntos
Colectomia , Neoplasias Colorretais/cirurgia , Mediadores da Inflamação/sangue , Laparoscopia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/imunologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , alfa-Defensinas/sangue , Idoso , Proteína C-Reativa/análise , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
8.
BMC Surg ; 11: 6, 2011 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-21366898

RESUMO

BACKGROUND: The myofibroblasts play a central role in wound healing throughout the body. The process of wound healing in the colon was evaluated with emphasis on the role of myofibroblasts. METHODS: One hundred male Wistar rats weighing 274 ± 9.1 g (mean age: 3.5 months) were used. A left colonic segment was transected and the colon was re-anastomosed. Animals were randomly divided into two groups. The first group experimental animals (n = 50) were sacrificed on postoperative day 3, while the second group rats (n = 50) were sacrificed on postoperative day 7. Healing of colonic anastomosis was studied in terms of anastomotic bursting pressure, as well as myofibroblastic reaction and expression of α-smooth muscle actin (α-SMA), adhesion formation, inflammatory reaction and neovascularization. RESULTS: The mean anastomotic bursting pressure increased from 20.6 ± 3.5 mmHg on the 3rd postoperative day to 148.8 ± 9.6 Hg on the 7th postoperative day. Adhesion formation was increased on the 7th day, as compared to the 3rd day. In addition, the myofibroblastic reaction was more profound on the 7th postoperative day in comparison with the 3rd postoperative day. The staining intensity for α-SMA was progressive from the 3rd to the 7th postoperative day. On the 7th day the α-SMA staining in the myofibroblats reached the level of muscular layer cells. CONCLUSIONS: Our study emphasizes the pivotal role of myofibroblasts in the process of colonic anastomosis healing. The findings provide an explanation for the reduction in the incidence of wound dehiscence after the 7th postoperative day.


Assuntos
Colo/cirurgia , Miofibroblastos/metabolismo , Cicatrização/fisiologia , Actinas/biossíntese , Anastomose Cirúrgica , Animais , Colo/irrigação sanguínea , Pressão Hidrostática , Inflamação , Masculino , Neovascularização Fisiológica , Distribuição Aleatória , Ratos , Ratos Wistar , Aderências Teciduais
9.
World J Gastroenterol ; 12(30): 4927-9, 2006 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-16937485

RESUMO

Villous adenomas of the bile ducts are extremely uncommon. We describe a 58-year-old man presenting with clinical signs and laboratory findings of acute pancreatitis and obstructive jaundice. Preoperative investigation demonstrated a dilated papillary orifice with mucus exiting (fish-mouth sign) and a filling defect in the distal common bile duct. He underwent a modified Whipple operation and histological examination of the surgical specimen showed villous adenoma with rich secretion of mucus.


Assuntos
Adenoma de Ducto Biliar/complicações , Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos/patologia , Mucinas/metabolismo , Pancreatite/etiologia , Adenoma de Ducto Biliar/patologia , Adenoma de Ducto Biliar/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/patologia , Icterícia Obstrutiva/cirurgia , Masculino , Pessoa de Meia-Idade , Pancreatite/patologia , Pancreatite/cirurgia , Resultado do Tratamento
10.
World J Gastrointest Surg ; 8(6): 461-6, 2016 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-27358679

RESUMO

Solitary fibrous tumor (SFT) is a mesenchymal tumor typically located in the pleura, but can also be found as an asymptomatic mass in other areas, including the liver, peritoneum, kidney and salivary glands. However, SFT rarely locates in the pancreas. We present such a case of pancreatic SFT, along with a review of all reported cases. A 55-year-old man was treated surgically for an asymptomatic pancreatic mass after a rigorous preoperative control. Histologic examination of the resected specimen showed characteristics of an SFT. As only 15 cases of pancreatic SFT have been reported so far, an attempt to compare the cases was considered intriguing. We found that patients with pancreatic SFT were mainly women (81.25%), with a median age of 54 years at the time of diagnosis and a median tumor size of 5.83 cm. Pancreatic SFTs were revealed incidentally in 50% of cases, and all of them showed an enhancement through arterial computed tomography. All tumors were positive for CD34, ten were positive for Bcl-2, and twelve were negative for S100. The diagnosis of this pancreatic tumor is established by a combination of clinical suspicion, imaging procedures and histological findings, and is confirmed by immunohistochemical staining. Although the behavior of SFTs is rather benign, close clinical follow-up is recommended due to a potentially malignant nature.

11.
Int J Gastrointest Cancer ; 36(1): 29-38, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16227633

RESUMO

BACKGROUND: Although the TNM system is useful in predicting survival in resected colorectal cancer, heterogeneity within the same stages regarding prognosis exists. We are presenting a pooled analysis of prognostic factors from two randomized studies of adjuvant treatment conducted by the Hellenic Cooperative Oncology Group. PATIENTS AND METHODS: Patients with stage II or III colon (n = 279) or rectal (n = 220) cancer were included in this analysis. Following surgery, patients received: 5-fluorouracil/leucovorin (5-FU/LV) (n = 135), 5-FU/LV and interferon Alfa-2a (IFNA-2a) (n = 138), 5-FU/LV and pelvic chemoradiotherapy (n = 106), and pelvic chemoradiotherapy alone (n = 108). RESULTS: Median follow up was 92 mo. The number of involved lymph nodes (LNs), tumor differentiation, and the presence of regional implants were independent prognostic factors for both OS and TTP, while nerve invasion was only significant for TTP. Patients were stratified into three prognostic groups (low-risk: no LNs and grade 1/2; high-risk: > 3 LNs and grade 3/4; intermediate-risk: remaining patients) with distinct differences in 5-yr survival (84.7% vs 57.6% vs 32.4%) and 5-yr TTP (81.2% vs 54.5% vs 28.6%). CONCLUSION: The combination of clinicopathological prognostic factors can be more informative than the traditional TNM staging system. Such stratification may be necessary in randomized trials and could be useful in deciding the most appropriate adjuvant treatment strategies.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Leucovorina/administração & dosagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes , Estudos Retrospectivos , Análise de Sobrevida
12.
Tumori ; 91(4): 309-13, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16277094

RESUMO

BACKGROUND: The management of patients with fluoropyrimidine-resistant advanced colorectal cancer remains Investigational. Irinotecan and oxaliplatin have proved effective in first-line treatment in combination with 5-fluorouracil. STUDY DESIGN: From February 1998 to September 2002, 34 patients with 5-fluorouracil-pretreated advanced colorectal cancer were enrolled in the study. Median age was 67 years (range, 32-76) and median performance status was 1. Twenty-one patients had multiple liver metastases. Other sites of disease included lungs, abdomen, pelvis, lymph nodes, bones and skin. They received six 28-day cycles of oxaliplatin (85 mg/m2 in a 2-h infusion on days 1 and 15) and irinotecan (80 mg/m2 in a 30-minute infusion on days 1, 8 and 15 immediately following oxaliplatin). RESULTS: Thirteen patients (39%) completed treatment. The most common grade Ill-lV toxicities were diarrhea (27%), anemia (6%), neutropenia (18%), alopecia (6%) and peripheral neuropathy (6%). Thirteen patients (39%) received G-CSF support, and there were 2 episodes of febrile neutropenia. There were no treatment-related deaths. Six patients (18%) had a partial remission and another 11 (33%), disease stabilization. There were no complete remissions. Median time to progression was 6.6 months (range, 0.8-20.1) and median survival 10.6 months (range, 0.8-52.9). CONCLUSIONS: Irinotecan and oxaliplatin combination has modest activity as second line treatment of 5-fluorouracil-resistant advanced colorectal cancer. Further research is warranted for the development of more effective and less toxic regimens in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Grécia , Humanos , Incidência , Irinotecano , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Resultado do Tratamento
13.
Anticancer Res ; 34(9): 4949-62, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25202077

RESUMO

BACKGROUND: Several studies have recently indicated the prognostic or predictive role of several biomarkers in colorectal cancer. We sought to investigate the prognostic value of prostaglandin synthase 2 (PTGS2), cyclooxygenase 2 (COX2), thymidylate synthetase (TYMS), thymidine phosphorylase (TYMP), dihydropyrimidine dehydrogenase (DPYD) and topoisomerase I (TOPO1) in colorectal cancer patients treated with 5-FU-based regimens, such as De Gramont and FOLFOX in the adjuvant setting. MATERIALS AND METHODS: In total, 96 formalin-fixed paraffin-embedded and 30 fresh-frozen tumor tissue samples were evaluated using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction and microarray gene expression profiling, respectively. RESULTS: The majority of tumors exhibited protein overexpression of COX2 (69%), TYMS (75%) and TOPO1 (75%). There was a significant association of TYMP protein expression with T classification, gender and stage (p=0.040, p=0.041 and p=0.011, respectively). TOPO1 protein expression was correlated with TOPO1 mRNA expression and was positively associated with stage (p=0.002) and lymph node infiltration (p=0.004). In univariate analysis, patients with high TYMS mRNA expression were shown to have a significantly lower risk for progression and death (Wald's p=0.030 and p=0.015, respectively). However, in multivariate analysis, only a trend for decreased risk for death was shown in patients with high TYMS mRNA expression (Wald's p=0.083), while patients with high PTGS2 mRNA expression had a trend for lower risk for progression (p=0.064). Using supervised hierarchical clustering, based on the expression in fresh-frozen tumor tissue of PTGS2, TYMS, TYMP and DPYD, our 30 patients were separated into two clusters. One of the clusters was enriched with patients with infiltrated lymph nodes (p<0.05), suggesting that these genes might have an impact on the tumor's ability to metastasize. CONCLUSION: These findings indicate a possible prognostic role of TYMS mRNA expression and highlight a cluster of genes associated with nodal metastases that warrant further investigation in a larger cohort of patients with colorectal cancer treated with 5-FU-based adjuvant chemotherapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Perfilação da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Análise por Conglomerados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Timidilato Sintase/genética , Resultado do Tratamento
14.
J Med Case Rep ; 5: 128, 2011 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-21450062

RESUMO

INTRODUCTION: Primary intestinal tuberculosis is a rare variant of tuberculosis. The preferred treatment is usually pharmaceutical, but surgery may be required for complicated cases. CASE PRESENTATION: We report two cases of primary intestinal tuberculosis where the initial diagnosis was wrong, with colonic cancer suggested in the first case and a Crohn's disease complication in the second. Both of our patients were Caucasians of Greek nationality. In the first case (a 60-year-old man), a right hemicolectomy was performed. In the second case (a 26-year-old man), excision was impossible due to the local conditions and peritoneal implantations. Histopathology revealed an inflammatory mass of tuberculous origin in the first case. In the second, cell culture and polymerase chain reaction tests revealed Mycobacterium tuberculosis. Both patients were given anti-tuberculosis therapy and their post-operative follow-up was uneventful. CONCLUSIONS: Gastrointestinal tuberculosis still appears sporadically and should be considered in the differential diagnosis along with other conditions of the bowel. The use of immunosuppressants and new pharmaceutical agents can change the prevalence of tuberculosis.

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