RESUMO
BACKGROUND: To demonstrate whether extensive intraoperative peritoneal lavage (EIPL) could yield better results in overall survival and less recurrence, regardless of peritoneal cytology, compared to standard peritoneal lavage (SPL). METHODS: A prospective randomised multicenter study including 94 patients (47 per arm) to detect a 20% difference in 3-year overall survival in patients with locally advanced tumours without peritoneal carcinomatosis. Three samples of peritoneal fluid were obtained (at the beginning, the end of procedure and after the assigned peritoneal lavage). Clinicopathological and surgical data were analysed by group. Postoperative complications, location of recurrence and surgical approach were evaluated. Overall survival was calculated by the Kaplan-Meier method and the uni/multivariate analysis for prognostic factors was carried out using Cox regression analysis. RESULTS: A total of 86 patients were analysed (4 excluded per group). No statistical differences were observed in clinicopathological or surgical data between groups, considering both groups well-balanced for analysis. Overall survival at 3 years was 64.3% for SPL vs. 62.3% for EIPL (p 0.421). Only three patients had at least one positive peritoneal cytology (1:2). There were no differences regarding postoperative complications (SPL: 37.2% vs. EIPL: 32.5%, p 0.65) or between location of recurrence and number of recurrences. The number of recurrences did not differ between surgical approaches, but locoregional and peritoneal recurrences were fewer with the laparoscopic approach (p 0.048). CONCLUSIONS: The regular use of extensive peritoneal lavage in patients with locally advanced gastric cancer, regardless of peritoneal cytology, has not been effective as prophylaxis of peritoneal recurrence or better survival.
Assuntos
Cuidados Intraoperatórios/mortalidade , Recidiva Local de Neoplasia/mortalidade , Lavagem Peritoneal/métodos , Neoplasias Peritoneais/mortalidade , Neoplasias Gástricas/mortalidade , Idoso , Análise de Variância , Quimioterapia Adjuvante , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/secundário , Lavagem Peritoneal/mortalidade , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Estudos Prospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: The Extensive Intraoperative Peritoneal Lavage (EIPL) has been proposed as a practical prophylactic strategy to decrease the risk of peritoneal metastasis in gastric cancer. OBJECTIVE: To explore the safety and efficacy of the EIPL in our locally advanced gastric cancer patients. METHODS: This study is an open-label, double-center, single-arm phase II clinical trial developed at two tertiary hospitals from Recife (Pernambuco, Brazil). RESULTS: The study protocol was prematurely closed due to slow accrual after only 16 patients had been recruited to participate. Eight of them were excluded of the protocol study during the laparotomy, whereas four cases were also excluded from the per-protocol analysis. Two patients had died in hospital before 30 days and six were alive with no evidence of cancer relapses after a follow-up ranging from five to 14,2 months (median of 10.6 months). In the intention-to-treat analysis, three of eight patients suffered of gastrointestinal leakages and two of them had died. On a per-protocol basis, two of four patients presented this type of postoperative complication and one of them had died. All deaths occurred as a somewhat consequence of gastrointestinal leakages. CONCLUSION: We could not make any conclusion about the safety and efficacy of the EIPL, but the possibility of this approach might increase the rate of gastrointestinal leakage is highlighted.
Assuntos
Lavagem Peritoneal , Neoplasias Peritoneais/prevenção & controle , Neoplasias Gástricas/terapia , Adulto , Terapia Combinada , Intervalo Livre de Doença , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Período Pós-Operatório , Recidiva , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
The peritoneal cavity is the main site of gastric cancer recurrence after curative surgery. When this recurrence occurs, patients may experience bowel obstruction, dehydration and multiple hospital admissions. The therapeutic options that may decrease the rate of peritoneal recurrence and increase five years survival are intraoperative hyperthermic chemotherapy, extensive intraoperative peritoneal lavage and routine bursectomy. We herein review the oncological results of curative surgery for gastric cancer, its failure patterns and the risk factors for peritoneal recurrence. We also review the studies aiming to prevent peritoneal carcinomatosis.
La recurrencia peritoneal en el cáncer gástrico avanzado, luego de una cirugía con intención curativa es un problema que debe ser considerado una prioridad en nuestro país, debido a la alta proporción de pacientes con compromiso de la serosa gástrica al momento del diagnóstico, siendo el peritoneo el principal sitio de recurrencia luego de una cirugía con intención curativa en este grupo. Luego de la recurrencia peritoneal, los pacientes presentan un deterioro importante de la calidad de vida, principalmente por episodios de obstrucción intestinal, deshidratación y rehospitalizaciones. Se han realizado múltiples estudios en el extranjero de potenciales medidas que se pueden realizar durante la cirugía inicial con intención curativa que previenen la recurrencia. Algunas de estas medidas han disminuido la recurrencia peritoneal y aumentado la sobrevida a 5 años, como son la quimioterapia hipertérmica intraoperatoria, el lavado peritoneal extensivo y la bursectomía rutinaria, en pacientes seleccionados. El objetivo de la presente revisión es mostrar los resultados oncológicos de la cirugía curativa, los patrones de falla luego de una cirugía curativa, los factores de riesgo para una recurrencia peritoneal y los estudios que se han realizado en relación a la prevención de la carcinomatosis peritoneal.
Assuntos
Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Quimioterapia Adjuvante , Intervalo Livre de Doença , Marcadores Genéticos , Neoplasias Peritoneais/epidemiologia , Lavagem Peritoneal , Recidiva , Fatores de RiscoRESUMO
PURPOSE: To demonstrate the irreversible poisoning action of the acetone cyanohydrin (AC) in malignant cells. METHODS: Thirty male Swiss mice were inoculated with 1 x 10³ Ehrlich tumor (ET) cells. The mice were divided into three groups (n=10): CG (saline); ACG1 (1.864 mg/Kg of AC) and ACG2 (2.796 mg/Kg of AC), treated every 48 hours from day 3 until day 13. On day 15 the mice were euthanized and the number of viable cells in ascites was determined. In the meantime, ET cells were incubated with AC (0.5, 1.0, 2.0 µg/mL). Cell viability and percentage of growth inhibition (PGI) were checked after one, two, three, four, 18 and 24 hours. RESULTS: There was reduction in volume and number of viable cells in ACG1 and ACG2 compared to CG. In ACG1 one of the animals did not present ascites. In ACG2 two mice did not present ascites and in CG none of the mice present ascites. The action of AC was dose and time dependent and there was no significant difference among the three doses. CONCLUSION: The acetone cyanohydrin promoted reduction of the tumor and also prevented tumor development in 20% of the treated animals.
Assuntos
Anticarcinógenos/uso terapêutico , Carcinoma de Ehrlich/prevenção & controle , Cianetos/toxicidade , Inibidores do Crescimento/uso terapêutico , Nitrilas/uso terapêutico , Neoplasias Peritoneais/prevenção & controle , Compostos de Enxofre/metabolismo , Animais , Carcinoma de Ehrlich/patologia , Contagem de Células , Sobrevivência Celular , Masculino , Camundongos , Neoplasias Peritoneais/patologia , Distribuição AleatóriaRESUMO
PURPOSE: To demonstrate the irreversible poisoning action of the acetone cyanohydrin (AC) in malignant cells. METHODS: Thirty male Swiss mice were inoculated with 1x10³ Ehrlich tumor (ET) cells. The mice were divided into three groups (n=10): CG (saline); ACG1 (1.864 mg/Kg of AC) and ACG2 (2.796 mg/Kg of AC), treated every 48 hours from day 3 until day 13. On day 15 the mice were euthanized and the number of viable cells in ascites was determined. In the meantime, ET cells were incubated with AC (0.5, 1.0, 2.0 μg/mL). Cell viability and percentage of growth inhibition (PGI) were checked after one, two, three, four, 18 and 24 hours. RESULTS: There was reduction in volume and number of viable cells in ACG1 and ACG2 compared to CG. In ACG1 one of the animals did not present ascites. In ACG2 two mice did not present ascites and in CG none of the mice present ascites. The action of AC was dose and time dependent and there was no significant difference among the three doses. CONCLUSION: The acetone cyanohydrin promoted reduction of the tumor and also prevented tumor development in 20% of the treated animals.
Assuntos
Animais , Masculino , Camundongos , Anticarcinógenos/uso terapêutico , Carcinoma de Ehrlich/prevenção & controle , Cianetos/toxicidade , Inibidores do Crescimento/uso terapêutico , Nitrilas/uso terapêutico , Neoplasias Peritoneais/prevenção & controle , Compostos de Enxofre/metabolismo , Contagem de Células , Sobrevivência Celular , Carcinoma de Ehrlich/patologia , Neoplasias Peritoneais/patologia , Distribuição AleatóriaRESUMO
Fatty acid synthase (FASN) is the enzyme responsible for the endogenous synthesis of the saturated fatty acid palmitate. In contrast to most normal cells, malignant cells depend on FASN activity for growth and survival. In fact, FASN is overexpressed in a variety of human cancers including cutaneous melanoma, in which its levels of expression are associated with a poor prognosis and depth of invasion. Here, we show that the specific inhibition of FASN activity by the antiobesity drug Orlistat or siRNA is able to significantly reduce proliferation and promote apoptosis in the mouse metastatic melanoma cell line B16-F10. These results prompted us to verify the effect of FASN inhibition on the metastatic process in a model of spontaneous melanoma metastasis, in which B16-F10 cells injected in the peritoneal cavity of C57BL/6 mice metastasize to the mediastinal lymph nodes. We observed that mice treated with Orlistat 48 hr after the inoculation of B16-F10 cells exhibited a 52% reduction in the number of mediastinal lymph node metastases, in comparison with the control animals. These results suggest that FASN activity is essential for B16-F10 melanoma cell proliferation and survival while its inactivation by Orlistat significantly reduces their metastatic spread. The chemical inhibition of FASN activity could have a potential benefit in association with the current chemotherapy for melanoma.