RESUMO
AIMS: This study assessed the techniques of the free jejunal graft for the reconstruction of hypopharynx or cervical esophagus and discussed the main aspects related to those procedures. METHODS AND RESULTS: By using free jejunal grafts, we reconstructed 54 hypopharyngeal and cervical esophageal cancers. In this study, 23 out of 54 patients had a malignant tumor located in the hypopharynx and 31 in the cervical esophagus (27 primary cases and four secondary cases). Despite the multi-step and time-consuming procedure, we did not incur any trans-operative complication. Furthermore, we undertook the larynx preserving cervical esophagectomy and free jejunal graft reconstruction in six patients with cervical esophageal cancer, and those patients acquired a good quality of life. CONCLUSION: For the reconstruction of hypopharynx or cervical esophagus, the free jejunal graft is a very useful technique and improves the patient's quality of life.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Neoplasias Hipofaríngeas/cirurgia , Jejuno/transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Endoscopia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esôfago/patologia , Feminino , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Hipofaringe/patologia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Qualidade de Vida , Fatores de Tempo , Resultado do TratamentoRESUMO
In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic invasion. Overexpression of heparanase in esophageal cancers was also associated with poor survival. In addition to its localization in the cytoplasm and cell membrane, heparanase was also identified in the nuclei of normal epithelial and tumor cells by immunohistochemistry. Furthermore, nuclear heparanase was detected in nuclear extract of cancer cell lines by Western blot and immunohistochemistry. Examination of the role of nuclear heparanase in cell proliferation and differentiation by double immunostaining for proliferating cell nuclear antigen (PCNA) and cytokeratin 10 (CK10) showed significant relationship between nuclear heparanase expression and differentiation (heparanase vs CK10), but not for proliferative state of esophageal cancer cells (heparanase vs PCNA). Our results suggest that cytoplasmic heparanase appears to be a useful prognostic marker in patients with esophageal cancer and that nuclear heparanase protein may play a role in differentiation. Inhibition of heparanase activity may be effective in the control of esophageal tumor invasion and metastasis.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Neoplasias Esofágicas/enzimologia , Glucuronidase/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Diferenciação Celular , Divisão Celular , Linhagem Celular Tumoral/enzimologia , Linhagem Celular Tumoral/patologia , Transformação Celular Neoplásica , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Glucuronidase/genética , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Taxa de SobrevidaRESUMO
5-fluorouracil (5-FU) is used for the treatment of stomach and colon cancer, but many tumors are resistant to this chemotherapeutic agent. 5-FU induces apoptosis of several cancer cell lines, while some chemotherapeutic agents are known to activate the transcriptional factor NF-kappaB, which strongly suppresses apoptosis in vitro. In the present study, we investigated the relationship between activation of NF-kappaB and chemoresistance to 5-FU in human stomach cancer cell lines, NUGC3 (5-FU sensitive) and NUGC3/5FU/L (5-FU resistant). Treatment with 5-FU for 9-12 h caused activation of inducible NF-kappaB in NUGC3/5FU/L cells but not in NUGC3 cells. 5-FU also resulted in an increase in the number of TUNEL-positive cells and enhanced caspase-3 activity 3- to 5-fold in NUGC3 cells but not NUGC3/5FU/L cells. Moreover we also demonstrated that the inhibition of inducible NF-kappaB activation by using a NF-kappaB decoy could induce apoptosis and reduce chemoresistance against 5-FU. Our results suggest that 5-FU chemoresistance can be overcome by inhibition of inducible NF-kappaB activation, and that the use of the NF-kappaB decoy combined with 5-FU treatment is a new molecular and gene therapeutic strategy aimed at treatment of human stomach cancers resistant to 5-FU.
Assuntos
Antimetabólitos Antineoplásicos/agonistas , Carcinoma/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/agonistas , NF-kappa B/análogos & derivados , NF-kappa B/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/genética , Antimetabólitos Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/genética , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/genética , Carcinoma/genética , Carcinoma/metabolismo , Caspase 3 , Caspases/efeitos dos fármacos , Caspases/metabolismo , Sinergismo Farmacológico , Fluoruracila/toxicidade , Humanos , NF-kappa B/metabolismo , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética , Células Tumorais CultivadasRESUMO
Degradation of basement membrane and extracellular matrix structures are important features of the metastatic process of malignant tumors. Human heparanase degrades heparan sulfate proteoglycans, which represent the main components of basement membranes and the extracellular matrix. Because of the role of heparanase in tumor invasion and metastasis, we examined heparanase expression in primary gastric cancers and in cell lines derived from gastric cancers by immunohistochemistry and RT-PCR, respectively. Four of seven gastric cancer cell lines showed heparanase mRNA expression by RT-PCR. Heparanase protein was detected in both the cytoplasm and the nucleus of heparanase mRNA-positive cells by immunohistochemical staining. Heparanase expression was confirmed in 35 (79.5%) of 44 gastric tumor samples by immunohistochemical staining. However, no or weak heparanase expression was detected in normal gastric mucosa. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Analysis of the clinicopathologic features showed stronger heparanase expression in cases of huge growing tumors, extensive invasion to lymph vessels, and regional lymph node metastasis. In gastric cancer, patients with heparanase expression showed significantly poorer prognosis than those without such expression (p = 0.006). In conclusion, our findings suggest that high expression of heparanase in gastric cancer is a strong predictor of poor survival.
Assuntos
Glucuronidase/análise , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Animais , Glucuronidase/genética , Glucuronidase/fisiologia , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , RNA Mensageiro/análise , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
We report a case of suture line recurrence in a jejunal pouch, diagnosed 4 months after total gastrectomy for advanced gastric cancer. The jejunal pouch was made with a linear stapler, without intraluminal irrigation being carried out before anastomosis, and was replaced in an interposition fashion. We propose that the recurrence was caused by the implantation of exfoliated cancer cells in either the intraluminal mucus or on a contaminated stapling device.