BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES.

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.

Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

Brazilian consensus for multimodal treatment of colorectal liver metastases. module 3: controversies and unresectable metastases / Consenso brasileiro de tratamento multidisciplinar de metástase hepática de origem colorretal módulo 3: controvérsias e metástases irressecáveis

ABSTRACT In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.

RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.

I BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 2: APPROACH TO RESECTABLE METASTASES.

BACKGROUND: Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients. AIM: In the second module of this consensus, management of resectable liver metastases was discussed. METHOD: Concept of synchronous and metachronous metastases was determined, and both scenarius were discussed separately according its prognostic and therapeutic peculiarities. RESULTS: Special attention was given to the missing metastases due to systemic preoperative treatment response, with emphasis in strategies to avoid its reccurrence and how to manage disappeared lesions. CONCLUSION: Were presented validated ressectional strategies, to be taken into account in clinical practice.

I brazilian consensus on multimodal treatment of colorectal liver metastases. module 2: approach to resectable metastases / I consenso brasileiro de tratamento multidisciplinar de metástase hepática colorretais módulo 2: manejo das metástases ressecáveis

Background : Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients. Aim : In the second module of this consensus, management of resectable liver metastases was discussed. Method : Concept of synchronous and metachronous metastases was determined, and both scenarius were discussed separately according its prognostic and therapeutic peculiarities. Results : Special attention was given to the missing metastases due to systemic preoperative treatment response, with emphasis in strategies to avoid its reccurrence and how to manage disappeared lesions. Conclusion : Were presented validated ressectional strategies, to be taken into account in clinical practice.

Racional: As metástases hepáticas de câncer colorretal são evento frequente e potencialmente fatal na evolução dos pacientes. Objetivo : No segundo módulo desse consenso, foi discutido o manejo de metástases hepáticas ressecáveis. Método : Foi definido o conceito de metástases síncrônicas e metacrônicas, e ambos os cenários foram discutidos separadamente de acordo com as suas peculiaridades prognósticas e terapêuticas. Resultados : Foi dada especial atenção às missing metástases em resposta ao tratamento pré-operatório sistêmico, com ênfase em estratégias para evitar sua recorrência e como gerenciar as lesões desaparecidas. Conclusão : Foram apresentadas e validadas estratégias de ressecção em várias circunstâncias, para serem aplicadas na prática clínica.

Type IV Borrmann gastric adenocarcinoma: analysis of curative resection results.

OBJECTIVE: To evaluate the results obtained with curative resection of Borrmann IV gastric adenocarcinoma (B IV) through the analysis of clinical, surgical and pathological data, identifying which of these prognostic factors were associated with survival. METHODS: We retrospectively analyzed 123 patients with B IV gastric adenocarcinoma undergoing surgical treatment at the Department of the pelvic-abdominal surgeries of the National Cancer Institute (INCA) from January 1997 to December 2005. The group undergoing curative resection was examined for various prognostic factors regarding overall survival. RESULTS: Of the 123 patients studied, 68 underwent gastrectomy, 52 (42.3%) with curative intent and 16 (13%) palliative resection, while 55 (44.7%) had disease not subject to resection. Three postoperative deaths followed the curative resection, constituting a mortality rate of 5.76%. In nine (17.3%) patients there were technical complications, and esophagojejunal fistula seven cases, the most frequent. All technical complications and deaths occurred after total gastrectomy, which was the most commonly performed curative resection type in this series. The most common pattern of recurrence was peritoneal carcinomatosis. The location of the tumor, lymph node metastasis, lymphatic invasion and pathological staging were considered significant prognostic factors. The median survival time was 29 months, with a rate of five-year survival of 33% in patients undergoing curative resection. CONCLUSION: The curative resection of B IV gastric adenocarcinoma had a positive impact on survival of patients with the disease in stages IB, II and III, with up to 15 lymph nodes (pN2) and localized type.

Adenocarcinoma gástrico Borrmann tipo IV: análise dos resultados da ressecção curativa / Type IV Borrmann gastric adenocarcinoma: analysis of curative resection results

OBJETIVO: Avaliar o resultado obtido com a ressecção de intenção curativa do adenocarcinoma gástrico Borrmann IV(B IV), através da análise de variáveis clínicas, cirúrgicas e anatomopatológicas, identificando quais destes fatores prognósticos se associaram à sobrevida. MÉTODOS: Foram analisados retrospectivamente, no período de janeiro de 1997 a dezembro de 2005, 123 pacientes com adenocarcinoma gástrico B IV submetidos ao tratamento cirúrgico no Serviço de Cirurgia Abdômino-Pélvica do Instituto Nacional de Câncer (INCA). O grupo submetido à ressecção curativa teve analisado diversos fatores prognósticos com relação à sobrevida global. RESULTADOS: Dos 123 pacientes estudados, 68 foram submetidos à gastrectomia, 52 (42,3 por cento) com intenção curativa e 16 (13 por cento) como ressecção paliativa, enquanto 55 (44,7 por cento) tiveram doença não passível de ressecção. Três óbitos no pós-operatório seguiram-se à ressecção curativa, configurando uma taxa de mortalidade de 5,76 por cento. Em nove (17,3 por cento) pacientes ocorreram complicações técnicas, sendo a fístula esofagojejunal com sete casos, a mais frequente. Todos os óbitos e complicações técnicas ocorreram após gastrectomias totais, que foi o tipo de ressecção curativa mais realizada nesta série. O padrão de recidiva mais comum foi a carcinomatose peritoneal. A localização do tumor, metástase linfonodal, invasão linfática e estadiamento patológico foram considerados fatores prognósticos significantes. O tempo de sobrevida mediano foi de 29 meses, com taxa de sobrevida em cinco anos de 33 por cento nos pacientes submetidos à ressecção curativa CONCLUSÃO: A ressecção com intenção curativa do adenocarcinoma gástrico B IV apresentou um impacto positivo na sobrevida dos pacientes com a doença nos estágios IB, II e III; com até 15 linfonodos comprometidos (pN2) e no tipo localizado.

OBJECTIVE: To evaluate the results obtained with curative resection of Borrmann IV gastric adenocarcinoma (B IV) through the analysis of clinical, surgical and pathological data, identifying which of these prognostic factors were associated with survival. METHODS: We retrospectively analyzed 123 patients with B IV gastric adenocarcinoma undergoing surgical treatment at the Department of the pelvic-abdominal surgeries of the National Cancer Institute (INCA) from January 1997 to December 2005. The group undergoing curative resection was examined for various prognostic factors regarding overall survival. RESULTS: Of the 123 patients studied, 68 underwent gastrectomy, 52 (42.3 percent) with curative intent and 16 (13 percent) palliative resection, while 55 (44.7 percent) had disease not subject to resection. Three postoperative deaths followed the curative resection, constituting a mortality rate of 5.76 percent. In nine (17.3 percent) patients there were technical complications, and esophagojejunal fistula seven cases, the most frequent. All technical complications and deaths occurred after total gastrectomy, which was the most commonly performed curative resection type in this series. The most common pattern of recurrence was peritoneal carcinomatosis. The location of the tumor, lymph node metastasis, lymphatic invasion and pathological staging were considered significant prognostic factors. The median survival time was 29 months, with a rate of five-year survival of 33 percent in patients undergoing curative resection. CONCLUSION: The curative resection of B IV gastric adenocarcinoma had a positive impact on survival of patients with the disease in stages IB, II and III, with up to 15 lymph nodes (pN2) and localized type.

What is the prognostic significance of metastatic lymph nodes in GIST?

BACKGROUND/AIMS: So many variables have been identified as prognostic factors influencing survival after curative resection in gastrointestinal stromal tumors (GIST), but the role of lymph node metastasis remains uncertain. METHODOLOGY: Twenty-nine patients with c-Kit positive gastric GIST who underwent surgical resection at the Brazilian National Cancer Institute between 1983 and 2004 were reviewed retrospectively. The prognostic significance of lymph node metastasis was investigated. The endpoints were overall survival and disease free survival. RESULTS: The median follow-up was 35 months. The 5-years estimate survival rate was 53%. Three patients presented lymph node metastasis and developed recurrence disease. Univariate analysis for overall survival identified the size >13.5cm (p = 0.01) and recurrence (p = 0.03) as prognostic factors. Size > 13.5cm and recurrence were independent factors (p = 0.01 and p = 0.03, respectively) in the multivariate analysis. Univariate analysis for disease free survival identified the size > 13.5cm (p = 0.04) and the grade (p = 0.04) as prognostic factors but, only the size > 13.5cm was an independent factor in the multivariate analysis. Lymph node metastasis had no prognostic significance for overall and disease free survival (p = 0.65 and p = 0.57, respectively). CONCLUSIONS: GIST lymph node metastasis was not related to poor survival in this study, but more studies are needed to identify the real incidence and the proper role of the GIST metastatic nodal disease.

Câncer colo-retal hereditário / Colorectal hereditary cancer- update

The colorectal cancer has become a world public health problem as a consequence of the great number of new cases which have been diagnosed each year and the existence of some conditions related to the disease's natural history that can be identified and the cancer prevented. Knowing the fact that 20 percent out of all colorectal cancers develops as part of a hereditary cancer syndrome, it is crucial that the physician (not only the surgeon) be updated with this entity, being able to recognize, and mainly, implement screening programs to identify family members at risk of developing cancer and to allow the intervention to prevent the occurrence of the adenoma-carcinoma sequence.

Effects of alpha-tocopherol on bacterial translocation and lipid peroxidation in rats with intestinal obstruction

PURPOSE: Investigate if alpha-tocopherol has a protective effect on intestinal mucosa after obstruction and to evaluate the potential relations between lipid peroxidation and bacterial translocation. METHODS: Ten rats were submitted to a sham laparotomy and six served as control group. A small bowel obstruction was done in sixteen animals and among them eight were pretreated with alpha-tocopherol. Forty-eight hours later, mesenteric lymph node, spleen, liver and blood cultures and also samples from ileal mucosal were obtained, Thiobarbituric acid reactive substances (TBARS) levels were determined and intestinal histological assessment was performed. RESULTS: Bacterial translocation was significantly increased in the obstructed rats compared with the control, sham and antioxidant pretreated groups (p< 0,05). TBARS (nmol/100mg) in untreated obstructed rats increased from 49,0 ± 13,3 in control group to 128,8 ± 40 after 48 hours of intestinal obstruction and achieved 72,3 ± 24,6 in alpha-tocopherol group (p< 0,05). Bacterial adherence to the intestinal epithelial cells surface and mucosal necrosis were significantly increased in the obstructed compared with nonobstructed rats. CONCLUSION: Alpha-tocopherol reduce the deleterious effects of the TBARS over the intestinal mucosal suggesting that in such circumstances there might be an association between bacterial translocation and lipid peroxidation after an intestinal occlusion.

Colitis following fecal diversion: still a challenge

After fecal diversion, nonspecific colitis may be seen in the defunctionalized colon. The purpose of this prospective study is to identify specific findings that could help in the differential diagnosis between diversion colitis and other inflammatory bowel diseases in order to avoid inappropriate diagnosis and therapy. It was studied, prospectively, thirteen consecutive patients from two public hospitals of Rio de Janeiro who had undergone temporary colostomy for indications other than inflammatory bowel disease. They were submitted to endoscopy with biopsy of both proximal and distal colorectal segments, and prospectively evaluated before and after restoration of intestinal continuity. Endoscopy with biopsy of both proximal and distal excluded colorectal segments showed a nonspecific mucosal and submucosal inflammation, resembling ulcerative colitis ( p < 0.01). There was endoscopic resolution in all patients once restoration of intestinal continuity was established (p < 0.01) and also histologic improvement after the stoma closure. In conclusion there are no specific findings that make possible an unequivocal distinction between diversion colitis and other nonspecific inflammatory diseases. Diagnosis should be achieved if after stoma closure occur remission of endoscopic large bowel inflammatory signs with improvement in mucosal histologic appearance and prompt relief of clinical complaints.

Translocação bacteriana e peroxidação lipídica na obstrução intestinal em ratos

Infecção sistêmica por bacilos gram negativos é uma importante causa de morbimortalidade na síndrome de obstrução intestinal. O objetivo deste estudo foi verificar a incidência de translocação bacteriana e avaliar o papel da peroxidação lipídica na oclusão intestinal. Dez ratos da linhagem Am-1-tor, machos, foram submetidos à laparotomia com manipulação das alças ntestinais (grupo II ou sham) dezesseis ratos à aobstrução ileal completa (grupo III); seis ratos foram tratados profilaticamente com tocoferol intramuscular (500mg/kg) e submetidos à ligadura íleo terminal (grupo IV); e cinco ratos não laparotomizados serviram como grupo controle (grupo I). Translocação bacteriana foi verificada através de estudo bacteriológico quantitativo e qualitativo de linfonodos mesentéricos, baço, fígado e sangue. A população bacteriana aeróbica do intestino, a dosagem de substâncias reativas com o ácido tiobarbitúrico (SRATB) da mucosa ileal foram aliadas. A análise morfológica intestinal foi realiazada. Os testes do qui-quadrado, de Brieger e de Kruskal-Wallis foram utilizados na análise estatística dos resultados. A ocorrência de translocação bacteriana foi significativamente superior nos ratos obstruídos (grupo III=46,9 por cento) comparados aos do grupo controle (4,2 por cento), sham (10 por cento)e àqueles obstruídos que receberam profilaticamente tocoferol (grupo IV=20,8 por cento) (p<0,05). Os níveis de SRATB (nanomoles/g) nos ratos obstrúidos do grupo III aumentaram de 49±13,3, observados no grupo controle para 97,0±26,4 e 128,8±40 após 24h e 48h de oclusão intestinal, respectivamente. No grupo IV, o aumento de SRATB para 72,3±24,6 foi significativamente menor (p<0,05). A população bacteriana entérica, a aderência de bactérias à superficíe epitelial e a necrose da mucosa intestinal foram eventos mais comuns nos grupos submetidos à obstrução comparados aos grupos controle e sham, assim como alterada relação vilosidade/cripta. Conclui-se que tocoferol reduziu a incidência de translocação bacteriana, os níveis de SRATB na mucosa ileal e as alterações morfológicas da parede do intestino, sugerindo uma associação entre translocação bacteriana e peroxidação na obstrução intestinal.

Gram negative septic events are an important source of morbidity and mortality as a result of intestinal occlusion. The purpose of this study was to investigate the incidence of bacterial translocation and to assess the role of intestinal mucosal thiobarbituric acid reactive substances (TBARS) levels, as indicator of lipid peroxidation, in ileal obstruction. Ten male rats were subjected to sham laparotomy (group II); sixteen rats to complete occlusion of distal ileum (group III); six rats were pretreated with intramuscular a-tocopherol (500mglkg) on day 7,3 and 0 before of intestinal obstruction (group IV); five rats served as a nonoperated control group (group I). The animals were tested for bacterial translocation through quantitative and qualitative bacteriological studies from mesenteric lymph node, spleen, liver and blood. The enteric bacteriological population was studied. Ileal mucosal TBARS levels were determined and intestinal histological assessment was performed. For statistical analysis the quisquare, Brieger and Kruskal- Wallis tests were used. Bacterial translocation was significantly increased in the obstructed rats (group III=46,9%) compared with the control (group I=4,2%), sham (group II=10%) and pretreated obstructed rats (group IV=20,8%) (p<0,05). neal mucosal TBARS (nanomoleslg) in untreated obstructed rats increased from 49,0±13,3 in control group to 97,0±26,4 and 128,8±40 after 24h and 48h intestinal obstruction, respectively. In the (a-tocopherol group the increase of TBARS to 72,3±24,6 was significantly lower (p

Colite relacionada à derivação fecal

Uma forma de colite, denominada colite relacionada à derivação fecal, foi observada em segmentos colônicos excluídos identificar e caracterizar esta nova afecção, estabelecer critérios epidemiológicos, endoscópios e histopatológicos para seu diagnóstico, bem como observar sua evolução após reanastomose colônica. Em 13 pacientes avaliados sem prévia história doscópicos e histológicos desta afecção foram o de um processo inflamatório inespecífico, indistinguível daquele apresentado por colite ulcerativa. Os portadores de colite de derivação eram usualmente oligossintomáticos. Após cirurgia de reconstrução do trânsito intestinal houve regressão das alterações inflamatórias no colo-reto refuncionalizado, o que torna a cirurgia de reanastomose colônica sua forma de tratamento definitivo

Colite relacionada à derivação fecal

Uma forma de colite, denominada colite relacionada à derivação fecal, foi observada em segmentos colônicos excluídos do trânsito fecal. O presente estudo prospectivo objetivou identificar e caracterizar esta nova afecção, estabelecer critérios epidemiológicos, endoscópicos e histopatológicos para seu diagnóstico, bem como observar sua evolução após reanastomose colônica. Em 13 pacientes avaliados sem prévia história de doença inflamatória intestinal inespecífica, os aspectos endoscópicos e histológicos desta afecção foram o de um processo inflamatório inespecífico, indistinguível daquele apresentado por colite ulcerativa. Os portadores de colite de derivação eram usualmente oligossintomáticos. Após cirurgia de reconstrução do trânsito intestinal houve regressão das alterações inflamatórias no colo-reto refuncionalizado, o que torna a cirurgia de reanastomose colônica sua forma de tratamento definitivo

A form of colitis named divertion related colitis was observed in segments of excluded colon from the fecal stream by a diverting colostomy. This prospective study aimed to recognize this new pathology and to know its evaluation after the reestablishment of continuity of bowel. We studied 13 patients with no previous history of inflammatory bowel disease. Patients were usually oligossymptomatic. Their endoscopic and histologic features resembled those of active ulcerative colitis. There was resolution once continuity of the colon was reestablished in alI patients

Radiacais livres de oxigênio. Aspectos químicos, biológicos e fisiopatológicos em medicina / Free radicals from oxigen. Chemical, biologic and physiopathological aspects in medicine

Os autores atualizam os conhecimentos relativos aos radicais livres de oxigênio (RLO) como importantes mediadores da injúria celular, revisando sua biogeraçäo em sistemas biológicos e sua citotoxicidade, com ênfase para os aspectos fisiopatológicos da peroxidaçäo lipídica (PL) e dos distúrbios do cálcio intracelular.