Intraperitoneal chemotherapy for gastric cancer with peritoneal carcinomatosis: study protocol of a phase ii trial / Quimioterapia intraperitoneal para o câncer gástrico com carcinomatose peritoneal: protocolo de estudo de um ensaio de fase ii

ABSTRACT BACKGROUND: Peritoneal carcinomatosis in gastric cancer is considered a fatal disease, without expectation of definitive cure. As systemic chemotherapy is not sufficient to contain the disease, a multimodal approach associating intraperitoneal chemotherapy with surgery may represent an alternative for these cases. AIMS: The aim of this study was to investigate the role of intraperitoneal chemotherapy in stage IV gastric cancer patients with peritoneal metastasis. METHODS: This study is a single institutional single-arm prospective clinical trial phase II (NCT05541146). Patients with the following inclusion criteria undergo implantation of a peritoneal catheter for intraperitoneal chemotherapy: Stage IV gastric adenocarcinoma; age 18-75 years; Peritoneal carcinomatosis with peritoneal cancer index<12; Eastern Cooperative Oncology Group 0/1; good clinical status; and lab exams within normal limits. The study protocol consists of four cycles of intraperitoneal chemotherapy with paclitaxel associated with systemic chemotherapy. After treatment, patients with peritoneal response assessed by staging laparoscopy undergo conversion gastrectomy. RESULTS: The primary outcome is the rate of complete peritoneal response. Progression-free and overall survivals are other outcomes evaluated. The study started in July 2022, and patients will be screened for inclusion until 30 are enrolled. CONCLUSIONS: Therapies for advanced gastric cancer patients have been evaluated in clinical trials but without success in patients with peritoneal metastasis. The treatment proposed in this trial can be promising, with easy catheter implantation and ambulatory intraperitoneal chemotherapy regime. Verifying the efficacy and safety of paclitaxel with systemic chemotherapy is an important progress that this study intends to investigate.

RESUMO RACIONAL: A carcinomatose peritoneal no câncer gástrico é considerada uma doença fatal, sem expectativa de cura definitiva. Como a quimioterapia sistêmica não é suficiente para conter a doença, uma abordagem multimodal associando a quimioterapia intraperitoneal à cirurgia pode representar uma alternativa para esses casos. OBJETIVOS: Investigar o papel da quimioterapia intraperitoneal em pacientes com câncer gástrico estágio IV com metástases peritoneais. MÉTODOS: Trata-se de um ensaio clínico prospectivo unicêntrico, braço único, fase II (NCT05541146). Pacientes com os seguintes critérios de inclusão serão submetidos à implantação de cateter peritoneal para quimioterapia intraperitoneal: adenocarcinoma gástrico estágio IV; idade 18-75 anos; carcinomatose peritoneal com índice de câncer peritoneal<12; ECOG 0/1; bom estado clínico e exames laboratoriais dentro da normalidade. O protocolo do estudo consiste em 4 ciclos de quimioterapia intraperitoneal com Paclitaxel associado à quimioterapia sistêmica. Após o tratamento, os pacientes com resposta peritoneal avaliada por laparoscopia serão submetidos à gastrectomia de conversão. RESULTADOS: O desfecho primário é a taxa de resposta peritoneal completa. A sobrevida livre de progressão e global são outros desfechos avaliados. O estudo foi iniciado em julho de 2022 e os pacientes serão selecionados para inclusão até que 30 sejam inscritos. CONCLUSIONS: Terapias para pacientes com câncer gástrico avançado foram avaliadas em ensaios clínicos, mas sem sucesso em pacientes com metástase peritoneal. O tratamento proposto neste estudo pode ser promissor, com fácil implantação do cateter e regime de quimioterapia intraperitoneal ambulatorial. Verificar a eficácia e segurança do Paclitaxel associado à quimioterapia sistêmica é um progresso importante que o presente estudo pretende investigar.

Assessing morbidity, mortality, and survival in patients with peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy / Avaliação da morbimortalidade e da sobrevida em pacientes portadores de carcinomatose peritoneal submetidos a cirurgia citorretorredutora e quimioterapia hipertérmica intraperitoneal (HIPEC)

ABSTRACT Peritoneal carcinomatosis (PC) indicates advanced stage cancer, which is generally associated with a poor outcome and a 6 to 12 months. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option for treating patients with primary PC, such as mesothelioma, or secondary PC, such as colorectal cancer (CRC) or pseudomixoma. Until recently, such patients were deemed untreatable. Objective: The purpose of this study was to assess the results of CRS + HIPEC in patients with PC. Postoperative complications, mortality and survival rates were evaluated according to the diagnosis. Results: Fifty-six patients with PC, undergoing full CRS + HIPEC between October 2004 and January 2020, were enrolled. The mortality rate was 3.8% and the morbidity rate was 61.5%. Complications were significantly higher in proportion to the duration of surgery (p<0.001). The overall survival rates, as shown in the Kaplan-Meyer curve, were respectively 81%, 74% and 53% at 12, 24 and 60 months. Survival rates according to each diagnosis for the same periods were 87%, 82% and 47% in patients with pseudomixoma, and 77%, 72% and 57% in patients with CRC (log-rank 0.371, p=0.543). Conclusion: CRS with HIPEC is an option for pacients with primary or secondary PC. Although complication rates are high, a longer survival rate may be attained compared to those seen in previously published results; in some cases, patients may even be cured.

RESUMO O diagnóstico de carcinomatose peritoneal (CP), indica um estágio avançado do câncer e em geral está associado a um mau prognóstico com sobrevida média variando de 6 a 12 meses. A cirurgia citorredutora (CRS) associada à quimioterapia intraperitoneal hipertérmica (HIPEC) tem sido descrita como uma opção de tratamento para os pacientes portadores de CP primária como nos portadores de mesotelioma, ou secundária como em portadores de cancer colorretal ou pseudomixoma, até recentemente considerados sem possibilidade terapêutica. Objetivo: Avaliar os resultados do tratamento de pacientes portadores de CP submetidos a CRS + HIPEC. Foram analisadas as taxas complicações pós-operatórias, mortalidade e a sobrevida desses pacientes. Resultados: Foram incluídos 56 pacientes com CP, submetidos a c CRS + HIPEC, no período de Outubro 2004 a Janeiro 2020. A taxa de mortalidade foi de 3,8% e taxa de morbidade de 61,5%, sendo a ocorrência de complicações significativamente maior quanto maior o tempo cirúrgico (p<0,001). A sobrevida global pela curva de Kaplan-Meyer foi de 81%, 74% e 53% em 12, 24 e 60 meses respectivamente. Já a sobrevida por diagnóstico nos mesmos períodos foi de 87%, 82%, 47% para os pacientes portadores de pseudomixoma e de 77%, 72% e 57% para pacientes portadores de câncer colorretal (Log -RANK 0,371, p=0,543). Conclusão: A CRS + HIPEC é uma opção de tratamento para pacientes portadores de CP primária ou secundária. Embora com taxa de complicações elevadas, pode proporcionar aumento da sobrevida quando comparado com resultados prévios da literatura e em alguns casos até a cura.

Medidas de segurança ocupacional no transoperatório de quimioterapia hipertérmica intraperitoneal: scoping review / Medidas de seguridad ocupacional en el transoperatorio de quimioterapia hipertérmica intraperitoneal: scoping review / Occupational safety measures in the intraoperative period of hyperthermic intraperitoneal chemotherapy: scoping review

Resumo Objetivo Mapear as medidas de segurança ocupacional recomendadas aos profissionais envolvidos no atendimento transoperatório de pacientes submetidos à Quimioterapia Intraperitoneal Hipertérmica. Métodos Estudo qualitativo com ênfase em scoping review, fundamentado no Instituto Joanna Briggs. Realizou-se buscas nas bases de dados Pubmed, BVS, ScIELO, Scopus, Web of Science, Google Scholar, The Chocrane Library e literatura cinzenta. Pergunta de pesquisa utilizou o acrônimo PCC: quais medidas de segurança ocupacional são necessárias no Centro Cirúrgico para profissionais que atuam, direta ou indiretamente, no transoperatório da HIPEC? A Busca de artigos ocorreu entre 2015 a 2019. Resultados Evidenciou-se escassa literatura sobre a temática. Selecionados dez artigos: uma revisão sistemática; dois casos-controle; dois estudos descritivos; quatro estudos de revisão bibliográfica; um relato de experiência. Análise dos artigos evidenciou as medidas de segurança recomendadas para profissionais que atuam direta ou indiretamente nesse procedimento cirúrgico, a saber: educação e capacitação da equipe envolvida; utilização de equipamentos de proteção individual e coletiva; oferecer infraestrutura e orientações gerais. Conclusão Medidas de segurança recomendadas para os profissionais envolvidos no atendimento transoperatório do paciente submetido à Quimioterapia Intraperitoneal Hipertérmica são: capacitação da equipe; utilização de equipamentos específicos de proteção individual e coletiva; infraestrutura necessária como ajuste do ar condicionado com pressão maior dentro da sala cirúrgica; e orientações gerais em relação à organização da sala cirúrgica, descarte dos resíduos, limpeza da sala/materiais utilizados e acompanhamento da saúde ocupacional da equipe envolvida em procedimento cirúrgico.

Resumen Objetivo Mapear las medidas de seguridad ocupacional recomendadas a los profesionales involucrados en la atención transoperatoria de pacientes sometidos a Quimioterapia Intraperitoneal Hipertérmica. Métodos Estudio cualitativo con énfasis en el scoping review, fundamentado en el Instituto Joanna Briggs. Se realizaron búsquedas en las bases de datos Pubmed, BVS, ScIELO, Scopus, Web of Science, Google Scholar, The Chocrane Library y literatura gris. Pregunta de encuesta utilizó el acrónimo PCC: ¿qué medidas de seguridad ocupacional se hacen necesarias en el Quirófano para profesionales que actúan, directa o indirectamente, en el transoperatorio de la HIPEC? La búsqueda de los artículos ocurrió entre el 2015 y el 2019. Resultados Se puso en evidencia una escasa literatura sobre la temática. Seleccionados diez artículos: una revisión sistemática; dos casos-control; dos estudios descriptivos; cuatro estudios de revisión bibliográfica; un relato de experiencia. Análisis de los artículos evidenció las medidas de seguridad recomendadas para profesionales que actúan directa o indirectamente en ese procedimiento quirúrgico, a saber: educación y capacitación del equipo involucrado; utilización de equipos de protección individual y colectiva; brindar infraestructura y orientaciones generales. Conclusión Representan medidas de seguridad recomendadas para los profesionales involucrados en la atención transoperatoria del paciente sometido a Quimioterapia Intraperitoneal Hipertérmica: capacitación del equipo; utilización de equipos específicos de protección individual y colectiva; infraestructura necesaria como ajuste del aire acondicionado con una presión más alta dentro del quirófano; y orientaciones generales con relación a la organización del quirófano, descarte de los deshechos, limpieza de la sala/materiales utilizados y acompañamiento de la salud ocupacional por el equipo involucrado en el procedimiento quirúrgico.

Abstract Objective To map the occupational safety measures recommended to professionals involved in the intraoperative care of patients undergoing Hyperthermic Intraperitoneal Chemotherapy. Methods Qualitative scoping review based on the Joanna Briggs Institute. Searches were performed in Pubmed, VHL, ScIELO, Scopus, Web of Science, Google Scholar, The Chocrane Library databases and gray literature. The PCC acronym was used in the research question: what occupational safety measures are necessary in the operating room for professionals working directly or indirectly in the intraoperative period of HIPEC? A search for articles published between 2015 and 2019 was performed. Results Literature on the subject was scarce. Ten articles were selected: a systematic review; two control cases; two descriptive studies; four literature review studies; an experience report. In the analysis of articles, the recommended safety measures for professionals who work directly or indirectly in this surgical procedure was evidenced, namely: education and training of the staff involved; use of individual and collective protective equipment; provision of infrastructure and general guidelines. Conclusion Recommended safety measures for professionals involved in the intraoperative care of patients undergoing Hyperthermic Intraperitoneal Chemotherapy are: team training; use of specific individual and collective protection equipment; necessary infrastructure, such as adjusting the air conditioning to higher pressure inside the operating room; and general guidelines regarding the organization of the operating room, waste disposal, cleaning of the room/materials used, and monitoring of the occupational health of the team involved in the surgical procedure.

Adenocarcinoma of the appendix with extra-appendicular spread: Clinico-surgical and histologic analysis of 27 cases. / Adenocarcinoma de apéndice con extensión extraapendicular: Análisis clínico-quirúrgico e histológico de 27 casos.

BACKGROUND AND OBJECTIVES: Appendiceal neoplasms with extra-appendiceal spread may show different clinical patterns with pseudomyxoma peritonei (PMP) being one of them. We analyse the results in a series of patients treated in our centre. MATERIAL AND METHODS: Retrospective study of patients operated on for appendiceal peritoneal carcinomatosis from January 2012 to May 2015. RESULTS: Twenty-seven consecutive patients were included. Median age 63 years (26-73); 14 were men. Peritoneal carcinomatosis index=16±8 (3-31). The suspected preoperative origins were appendix in 23, ovary in 3 and urothelial in one. Postoperative mortality in 2 patients (7.4%). The remaining 36% presented morbidity. Major morbidity (Clavien-Dindo grades 3 and 4) occurred in 3 patients (12%). CONCLUSIONS: Mucinous adenocarcinomas with extra-appendiceal spread may present as PMP with mucinous ascites, jelly-nodular carcinomatosis without ascites, nodular or desmoplasic plates carcinomatosis without jelly mass/nodules. Histology is not correlated to clinical picture. Preoperative diagnosis of mucinous ovarian cancer in peritoneal carcinomatosis scenario may increase the doubt of their ovarian origin and force an appendiceal origin to be ruled out.

Alterations in hemostasis during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently associated with coagulation impairment and perioperative blood transfusion. Our aim was to investigate the impact of each procedure step on hemostasis, as measured by rotational thromboelastometry™ (ROTEM), fibrinogen level and platelet count as a primary outcome, along with its relationship with transfusion needs. METHODS: A prospective longitudinal study was performed. Hemoglobin level, fibrinogen level, platelet count and ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), α-angle (EXTEM, INTEM, FIBTEM) were measured before the procedure, at the end of cytoreductive surgery and after HIPEC. Appropriate statistical tests were used for comparison. A P<.05 was considered as significant. RESULTS: Forty-one women, with median age 54 (range 34-76) were recruited. Cytoreductive surgery was followed by a reduction of hemoglobin level from 11,4±1,5g/dl to 10,6±1,6g/dl, a reduction of serum fibrinogen level from 269±69mg/dl to 230±48mg/dl (P<.01) and MCF decline from 20±10 to 16±8mm (P<.01), in the FIBTEM test. HIPEC was followed by no hemostatic impairment. The number of packed red blood cells administered during patients stay kept a mild significant relationship with both fibrinogen level (ρ = -0.5, P=.002), and MCF EXTEM values (ρ= -0.43, P=0.006), recorded after HIPEC. CONCLUSIONS: The mild observed hemostatic impairment appeared after cytoreductive surgery instead of HIPEC, involving surgical hemorrhage as the most likely responsible factor. Further studies are required to confirm a correlation between transfusion needs and postoperative hemostatic tests.