Fluid administration in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: neither too much nor too little

Abstract Introduction Intraoperative fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy plays an important role in postoperative morbidity. Studies have found an association between overload fluid therapy and increased postoperative complications, advising restrictive intraoperative fluid therapy. Our objective in this study was to compare the morbidity associated with restrictive versus non-restrictive intraoperative fluid therapy. Methods Retrospective analysis of a database collected prospectively in the Anesthesiology Service of Virgen del Rocío Hospital, from December 2016 to April 2019. One hundred and six patients who underwent complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were divided into two cohorts according to Fluid Therapy received 1. Restrictive ≤ 9 mL.kg-1.h-1 (34 patients), 2. Non-restrictive ≥ 9 mL.kg-1.h-1 (72 patients). Percentage of major complications (Clavien-Dindo grade III-IV) and length hospital stay were the main outcomes variables. Results Of the 106 enrolled patients, 68.9% were women; 46.2% had ovarian cancer, 35.84% colorectal cancer, and 7.5% peritoneal cancer. The average fluid administration rate was 11 ± 3.58 mL.kg-1.h-1. The restrictive group suffered a significantly higher percentage of Clavien-Dindo grade III-IV complications (35.29%) compared with the non-restrictive group (15.27%) (p= 0.02). The relative risk associated with restrictive therapy was 1.968 (95% confidence interval: 1.158-3.346). We also found a significant difference for hospital length of stay, 20.91 days in the restrictive group vs 16.19 days in the non-restrictive group (p= 0.038). Conclusions Intraoperative fluid therapy restriction below 9 mL.kg-1.h-1 in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was associated with a higher percentage of major postoperative complications.

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.

Application and prospect of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastasis from colorectal cancer / 中华肿瘤杂志

Colorectal cancer is one of the common malignant tumors in China, and its incidence is increasing with years. As the second most common metastatic site of colorectal cancer, peritoneum is difficult to diagnose early and with a poor prognosis. Systemic intravenous chemotherapy was used as the main treatment strategy for peritoneal metastasis in the past, but its systemic toxic and side effects were obvious, and it could not effectively control tumor progression. In recent years, the continuous development of surgical techniques, concepts, and equipment, as well as the introduction of new chemotherapy drugs and targeted drugs have significantly improved the quality of life and prognosis of patients with peritoneal metastasis of colorectal cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively eradicated the intraperitoneal free cancer cells and subclinical lesions, while reducing systemic side effects of chemotherapy drugs, and achieve the radical cure of the tumor at the macro and micro levels to the greatest extent. It has been used as the first-line treatment program for peritoneal metastasis of colorectal cancer at home and abroad. This article focuses on the analysis and summary of the survival efficacy, prognostic factor analysis, and chemotherapy safety of CRS+ HIPEC in the treatment of colorectal cancer peritoneal metastasis. The existing problems and controversies of HIPEC therapy are discussed simultaneously.

PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) en el tratamiento de la carcinomatosis peritoneal: primeros casos en Chile / PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) in the treatment of peritoneal carcinomatosis: first cases in Chile

Resumen Introducción: PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) Es una técnica que, vía laparoscopía, permite administrar quimioterapia en aerosol intraperitoneal, para el tratamiento de la carcinomatosis, ya sea para disminuir masa tumoral y aumentar la resecabilidad, o como paliación sintomática. Objetivo: Presentar los dos primeros casos de PIPAC en Chile, las consideraciones técnicas y revisión de la literatura. Pacientes y Método: Se describe la forma en que un programa PIPAC fue implementado en Clínica Las Condes. Se describe la técnica. Este procedimiento se realizó en dos pacientes, ambas portadoras de carcinomatosis con ascitis refractaria. Resultados: No hubo complicaciones. Alta a las 24 h. Ambas pacientes presentaron disminución de la ascitis, la que se ha mantenido a los seis meses de seguimiento. Discusión: PIPAC es una técnica emergente, que ha demostrado ser segura, con escasas complicaciones, cuya indicación incluye carcinomatosis por cáncer de colon y ovario y que se está extendiendo a páncreas, vía biliar y estómago. Su rol exacto está por definirse. Conclusiones: PIPAC es una técnica factible de realizar en nuestro país; sus resultados preliminares son alentadores y exentos de complicaciones.

Introduction: PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy is a technique that allows laparoscopic administration of aerosol chemotherapy in the peritoneum. This procedure is utilized for treatment of carcinomatosis, for debulk abdominal tumors, increasing resectability, or for palliation of abdominal symptoms. Aim: To present the first two cases of PIPAC performed in Chile, technical considerations and review of the literature. Patients and Method: The way this program was started at Clínica Las Condes is presented. The technique is described. This procedure was performed in two females, both with refractory ascites due to carcinomatosis. Results: The procedure was uneventfully and patients were discharged 24 hours later. Both patients showed important reduction of ascites, maintained at 6 months of followup. Discussion: PIPAC is a safe emerging technique, with low complication rate. It is indicated in carcinomatosis of colonic and ovarían origin and in selected cases of pancreatic, bile duct and gastric carcinomatosis. More prospective, randomized studies should be done to stablish its exact role. Conclusions: PIPAC is a feasible technique to perform in our country. Preliminary results are encouraging and no complications were observed.

Meta analysis of whether cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy can improve survival in patients with colorectal cancer peritoneal metastasis / 中华胃肠外科杂志

Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.

Safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.

Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

Complete cytoreductive surgery is the key to improving survival of colorectal cancer patients with peritoneal metastases: comment on PROPHYLOCHIP and PRODIGE 7 / 中华胃肠外科杂志

Peritoneal carcinomatosis (PC) is one of the difficult problems in the treatment of colorectal cancer (CRC). Based on several retrospective analyses of large samples and prospective randomized controlled studies (RCTs), NCCN and PSOGI recommend cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for selected CRC patients with mild to moderate PC. There are two important controversial issues in this field: the survival benefit of second-look surgery plus HIPEC for the patients with high risk of PC, and the specific benefit of HIPEC added to CRS for patients with PC. PROPHYLOCHIP found that second-look surgery plus HIPEC in patients at high risk of PC does not result in increased survival. PRODIGE 7 showed that overall survival (OS, 41.7 months vs. 41.2 months, P=0.99) and recurrence-free survival (RFS, 13.1 months vs. 11.1 months, P=0.43) were similar between the HIPEC group and non-HIPEC group, and suggested that HIPEC is not necessary for patients who underwent complete CRS. However, due to a series of problems in the design and implementation of this trial, the conclusion has caused great controversy and has not been widely recognized. Through detailed analysis and in-depth discussion, we believe that the benefit of HIPEC could not be denied according to PRODIGE 7. CRS + HIPEC is the embodiment and model of the concept of "Solid tumor treatment is surgery-based integrated treatment". CRS is the cornerstone of therapeutic strategies with curative intent for CRC PC and complete CRS is the key to improve the prognosis. Furthermore, HIPEC is an effective supplement to CRS.

Strategies of chemotherapy for peritoneal metastasis of gastrointestinal cancer / 中华胃肠外科杂志

Peritoneal metastasis of gastrointestinal cancer is an independent factor that seriously affects the prognosis of patients. The "seed-soil" theory is considered to be the main theory to explain peritoneal metastasis. Because of the small size of peritoneal metastatic nodules at the initial stage, early diagnosis is particularly difficult, therefore, the risk assessment of peritoneal metastasis is very important. Recently, the diagnosis methods have gradually developed from clinicopathological factors to cytology and molecular level. In addition, the integrated assessment of multiple groups including radiomics further enriches the accurate diagnosis of peritoneal metastasis. Peritoneal metastasis is a big challenge in the treatment of gastrointestinal cancer which may also lead to refractory malignant ascites, intestinal obstruction, cachexia and other related complications. At present, the treatment is based on systemic chemotherapy. The combination of surgery, intraperitoneal chemotherapy and HIPEC is an effective treatment for peritoneal metastasis of gastrointestinal cancer. How to enrich peritoneal metastasis patients with potential benefits, how to determine the timing of conversion surgery, how to further optimize the existing treatment plan, especially how to formulate treatment plan for patients after conversion surgery, call for improved study design and prospective randomized controlled trials. The goal of continuous efforts is to effectively prolong the survival of gastrointestinal cancer trials patients with peritoneal metastasis.

Quimioterapia intraperitoneal en aerosol presurizado (PIPAC) / Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

RESUMEN La técnica PIPAC se presenta como una variante de tratamiento para los pacientes con carcinomato sis peritoneal que no son candidatos a una resección. Se describen de manera detallada los pasos y el procedimiento quirúrgico para la administración de quimioterapia intraperitoneal presurizada con dispositivo PIPAC.

ABSTRACT Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a therapeutic option for patients with unresectable peritoneal carcinomatosis. The steps and the surgical technique of the PIPAC technique are thoroughly described.

Peritoneal carcinomatosis treated with cytoreductive surgery and intraperitoneal chemotherapy / Carcinomatose peritoneal tratada com cirurgia citoreductiva e quimioterapia intraperitoneal

ABSTRACT Introduction: To evaluate the combined treatment with cytoreductive surgery and intraperitoneal chemotherapy for peritoneal carcinomatosis arising from colorectal cancer, pseudomyxoma peritonei and mesothelioma. Methods: Data were obtained from 73 patients with peritoneal carcinomatosis arising from colorectal cancer (52.1%), pseudomyxoma peritonei (41.1%) or mesothelioma (6.8%) between 2002 and 2011. We reported the morbidity grade (II, III and IV), mortality and survival rates of the candidates after cytoreductive surgery and intraperitoneal chemotherapy. Results: 41 (56.2%) women participated, and the median age was 50 years. Thirty-nine patients (53.4%) underwent complete cytoreductive surgery and intraperitoneal chemotherapy. Patients who underwent a complete cytoreduction received intraperitoneal chemotherapy with mitomycin C, from which only 16/39 (41%) had hyperthermic intraperitoneal chemotherapy (41-42 °C). The overall morbidity rate was 23.3% and the grade III/IV complication rate was 12.3%. The overall mortality rate was 5.5%. The univariate analysis showed that cytoreductive surgery and intraperitoneal chemotherapy (p = .029), a blood transfusion (p = .002) and the operative time (p = .001) were significant for the occurrence of postoperative complications. Patients with peritoneal carcinomatosis from colorectal cancer who underwent complete cytoreductive surgery and intraperitoneal chemotherapy had overall survival rates of 81.3%, 12.5% and 12.5% at 1, 3 and 5 years, respectively. Patients with peritoneal carcinomatosis from pseudomyxoma peritonei who underwent complete cytoreductive surgery and intraperitoneal chemotherapy had overall survival rates of 84.2%, 77.7% and 77.7% at 1, 3 and 5 years, respectively. Conclusion: The combined treatment for peritoneal carcinomatosis may be performed safely with acceptable morbidity and mortality in a specialized unit setting. Although over half of patients underwent normothermic intraperitoneal chemotherapy, our results were comparable to results from others centers.

RESUMO Introdução: O objetivo foi avaliar o tratamento combinado da cirurgia citorredutora e quimioterapia intraperitoneal em pacientes com carcinomatose peritoneal secundária ao câncer colorretal, pseudomixoma peritoneal e mesotelioma. Métodos: Foram obtidos dados de 73 pacientes com carcinomatose peritoneal secundária ao cirurgia citorredutora (52.1%), pseudomixoma peritoneal (41,1%) ou mesotelioma (6,8%). Foram avaliados o grau de morbidade, a taxa de mortalidade e as taxas de sobrevida após a cirurgia citorredutora e quimioterapia intraperitoneal. Resultados: 41 (56,2%) pacientes do sexo feminino participaram, com média de idade de 50 anos. 39 pacientes (53,4%) foram submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal. Todos esses receberam Mitomicina C, sendo 16/39 (41%) quimioterapia intraperitoneal hipertérmica (41-42°C). A morbidade global foi 23,3%, com taxa de mortalidade global de 5,5%. A análise univariada mostrou que câncer colorretal e quimioterapia intraperitoneal (p = .029), transfusão sanguínea (p = .002) e tempo operatório (p = .001) foram associados com complicações pós-operatórias. Pacientes com carcinomatose peritoneal secundária ao cirurgia citorredutora submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal tiveram sobrevida global de 81,3%; 12,5% e 12,5% em 1, 3 e 5 anos, respectivamente. Os pacientes com pseudomixoma peritoneal que foram submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal tiveram sobrevida global de 84,2%; 77,7% e 77.7% em 1, 3 e 5 anos, respectivamente. Conclusão: O tratamento combinado para carcinomatose peritoneal é seguro quando realizado em centros terciários com experiência no procedimento. Embora mais da metade dos pacientes tenham sido submetidos a quimioterapia intraperitoneal normotérmica após a cirurgia citorredutora completa, os resultados podem ser comparados a de outros centros que utilizam exclusivamente a quimioterapia hipertérmica.

A prototype single-port device for pressurized intraperitoneal aerosol chemotherapy. Technical feasibility and local drug distribution

Abstract Purpose: To evaluate the technical feasibility and homogeneity of drug distribution of pressurized intraperitoneal aerosol chemotherapy (PIPAC) based on a novel process of intraperitoneal drug application (multidirectional aerosolization). Methods: This was an in vivo experimental study in pigs. A single-port device was manufactured at the smallest diameter possible for multidirectional aerosolization of the chemotherapeutic drug under positive intraperitoneal pressure. Four domestic pigs were used in the study, one control animal that received multidirectional microjets of 9 mL/sec for 30 min and three animals that received multidirectional aerosolization (pig 02: 9 mL/sec for 30 min; pigs 03 and 04: 3 mL/sec for 15 min). Aerosolized silver nitrate solution was applied for anatomopathological evaluation of intraperitoneal drug distribution. Results: Injection time was able to maintain the pneumoperitoneum pressure below 20 mmHg. The rate of moderate silver nitrate staining was 45.4% for pig 01, 36.3% for pig 02, 36.3% for pig 03, and 72.7% for pig 04. Conclusions: Intra-abdominal drug distribution had a broad pattern, especially in animals exposed to the drug for 30 min. Our sample of only four animals was not large enough to demonstrate an association between aerosolization and a higher silver nitrate concentration in the stained abdominal regions.

Quimioterapia hipertérmica intraperitoneal transoperatória: o que a enfermagem precisa saber / Intraoperative hyperthermic intraperitoneal chemotherapy: what nurses should know / Quimioterapia intraperitoneal hipertérmica transoperatória: qué necesita saber la enfermería

Objetivo: apresentar o estado do conhecimento científico sobre quimioterapia hipertérmica intraperitoneal transoperatória no tratamento da carcinomatose peritoneal e os cuidados de enfermagem pós-operatórios para pacientes submetidos a essa terapia. Métodos: apresentam-se aspectos técnicos da quimioterapia hipertérmica intraperitoneal transoperatória, suas complicações potenciais e cuidados de enfermagem pós-operatórios envolvidos. Resultados: destaca-se a importância dos cuidados de enfermagem, quais sejam: monitorar sinais vitais, perfusão periférica, débito cardíaco e pressão venosa central; avaliar dor; encorajar tosse e realização de exercícios de respiração profunda; registrar drenagem de ferida operatória e drenos; investigar ruídos intestinais; medir volume residual gástrico; promover mudanças de decúbito; avaliar resultados laboratoriais de exames sanguíneos; instituir balanço hídrico e; aferir peso corporal. Conclusão: a quimioterapia hipertérmica intraperitoneal transoperatória é terapia promissora no tratamento de pacientes com carcinomatose peritoneal. Entretanto, para ser bem-sucedida, a prestação de cuidados de enfermagem é fundamental.

Objective: to present the current state of scientific knowledge about intraoperative hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis, and postoperative nursing care for patients undergoing this therapy. Methods: the study describes technical aspects of intraoperative hyperthermic intraperitoneal chemotherapy, the potential complications and post-operative nursing care involved. Results: emphasis was placed on the importance of nursing care, viz.: monitoring of vital signs, peripheral perfusion, cardiac output, and central venous pressure; pain assessment; encouraging coughing and deep breathing exercises; recording drainage of surgical wound and drains; investigating bowel sounds; measuring gastric residual volume; ensuring change of decubitus; evaluating laboratory blood test results; establishing water balance; and measuring body weight. Conclusion: intraoperative hyperthermic intraperitoneal chemotherapy has been shown to be a promising therapy in treatment of patients with peritoneal carcinomatosis. However, to be successful, the nursing care provided is fundamental.

Objetivo: presentar el estado del conocimiento científico sobre quimioterapia intraperitoneal hipertérmica transoperatoria en el tratamiento de la carcinomatosis peritoneal y los cuidados de enfermería posoperatorios para pacientes sometidos a ella. Métodos: se presentan aspectos técnicos de la quimioterapia intraperitoneal hipertérmica transoperatoria, sus complicaciones potenciales y cuidados de enfermería posoperatorios involucrados. Resultados: se destaca la importancia de los cuidados de enfermería: monitorear señales vitales, perfusión periférica, débito cardíaco, presión venosa central; evaluar dolor; estimular la tos y realización de ejercicios de respiración profunda; registrar drenaje de herida operatoria y drenes; investigar ruidos intestinales; medir volumen residual gástrico; promover cambios de decúbito; evaluar resultados de análisis de sangre en laboratorio; establecer balance hídrico; verificar peso corporal. Conclusión: la quimioterapia intraperitoneal hipertérmica transoperatoria es terapia prometedora en el tratamiento de pacientes con carcinomatosis peritoneal. Sin embargo, para ser exitosa, la prestación de cuidados de enfermería es fundamental.

Effects of nivolumab in peritoneal carcinamatosis of malign melanoma in mouse model

Abstract Purpose: To evaluate the efficacy of nivolumab and comparison with dacarbazine (DTIC) on peritoneal carcinomatosis of malignant melanoma in mouse model. Methods: Mouse skin melanoma cells was injected under the capsule of the peritoneal surface in the left side of the abdomen. On postoperative day ten, mouses randomised into three groups. Group 1: Control, Group 2: HIPEC (Hyperthermic intraperitoneal chemotherapy) with DTIC and Group 3: HIPEC with Nivolumab. After the sacrification on postoperative day fifteen, peritoneum evaluated macroscopically and histopathologically by using peritoneal regression grading score (PRGS). Results: In the 15th day exploration, all animals developed extensive intraperitoneal tumor growth in Group 1. In Group 2 and Group 3 median tumor size was 0.7±0.3cm and 0.3±0.2cm respectively (p: 0.023). Peritoneal carcinomatosis index (PCI) were significantly lower in Group 3 than other groups (p: 0.019). The lowest total tumor nodules in group 3 was 4 ± 2. The PGRS score was found significantly lower in Group 3 than other groups (p: 0.03). Lymphocytic response rate was found higher in the Group 3. Conclusions: It has been found that nivolumab significantly better than DTIC on peritoneal metastases of malign melanoma in mouse models. Nivolumab treatment gives promising results with pathological evidence in the treatment of metastatic disease of malignant melanoma.

Citorreduccion con quimioterapia / Citorreduction with chemotherapy

Hasta no hace mucho tiempo el cancer en la superficio peritoneal estaba asociado con un pesimo pronostico. Esta forma extrema de presentacion de algunos tumores de origen peritoneal, digestivo o ginecologico, que se diseminan por vía transcelomica, tenía terapias solamente paliativas. En la actualidad algunos pacientes con diseminacion peritoneal del cancer pueden beneficiarse de un tratamiento que asocia cirugia de citorreduccion y quimoterapia intraperitoneal para brindar una alternativa terapeutica que puede mejorar el tiempo de supervivencia y la calidad de vida de las personas. En este trabajo intento demostrar el desarrollo y propositos de una cirugía desafiante en lo que respecta a nuestro rol como instrumentadores, la citorreducción. La misma consiste en la reseccion de toda enfermedad macroscopica, la que es visible al ojo humano sin ayuda de microscopio y luego la deliminación de la enfermedad microscopica mediante la utilización intraperitoneal de farmacos quimioterapicos a alta temperatura. En la actualidad el Sanatorio Allende es el unico centro de salud de la provincia de Cordoba y unos pocos en el pais, que tiene un programa de estas caracteristicas.

Rol de la cirugía citoreductora y quimioterapia hipertérmica en el tratamiento de la carcinomatosis peritoneal / Cytoreductive surgery and hyperthermic chemotherapy role in peritoneal carcinomatosis treatment

El objetivo de este artículo es ofrecer una revisión sobre algunas estrategias terapéuticas actuales para pacientes con carcinomatosis peritoneal (CP), la que históricamente ha sido considerada como una condición terminal, sólo susceptibles de tratamientos y cuidados paliativos; y ocasionalmente de qui-mioterapia sistémica aislada con mala respuesta y supervivencias promedio inferiores a los 6 meses. La combinación de cirugía de citoreductora (CCR), que implica peritonectomía y resecciones multiviscerales con hipertermia y quimioterapia intraperitoneal intraoperatoria (HIPEC), es un concepto relativamente nuevo en el tratamiento de la enfermedad microscópica residual intraperitoneal. La indicación de este método se ha ido extendiendo de forma progresiva, para pacientes con CP muy bien seleccionados; y tiene base en varios estudios de fase III, cuya conclusión es que se puede obtener suficiente citoreducción. Sin embargo, hasta el momento existe cierto consenso basado en la evidencia, en que estaría indicada en pacientes portadores de pseudomixoma peritoneal, mesotelioma peritoneal y cáncer colorrectal; y en CP de otro origen, dependiendo de cada caso en particular.

The aim of this article is to provide a review of some current therapeutic strategies for patients with peritoneal carcinomatosis (PC), which historically has been considered a terminal condition, only amenable to palliative care, and occasionally systemic chemotherapy alone with poor response and lower average survival. The combination of cytoreductive surgery (CRS), which involves peritonectomy and multivisceral resections and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a relatively new intraperitoneal treatment of microscopic residual disease concept. The indication of this method has been extended progressively to highly selected patients with PC and it is based in several phase III studies, which concluded that it is possible to obtain sufficient cytoreduction. However, until now there is some consensus based on evidence, in which HIPEC would be indicated in patients with peritoneal PC originated in pseudomyxoma, peritoneal mesothelioma and colorectal cancer; and CP from another source, depending on each particularcase.

Bevacizumab toxicity in heavily pretreated recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers / 부인종양

OBJECTIVE: Bevacizumab was recently approved by the US Food and Drug Administration for use in recurrent platinum resistant epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) when no more than two prior cytotoxic regimens have been used; due to concerns for gastrointestinal perforation. We sought to determine bevacizumab-related toxicities in heavily pretreated recurrent EOC. METHODS: We performed a retrospective chart review of patients with recurrent EOC, FTC, and PPC from 2001 to 2011. Patients who received at least two prior chemotherapy regimens before bevacizumab were included. Medical records were reviewed for bevacizumab associated toxicities. The Wilcoxon-Mann-Whitney test was used to compare quantitative variables. Survival was estimated with the Kaplan-Meier method. RESULTS: Sixty patients met inclusion criteria. At the start of bevacizumab treatment, the median age was 60 years and the median body mass index was 26.5 kg/m². More than 50% of patients received bevacizumab after three prior cytotoxic regimens. Grade 3 or higher bevacizumab associated toxicity events occurred in four patients, including one patient who developed a rectovaginal fistula. The median overall survival from the start of bevacizumab treatment was 21.05 months (95% CI, 18.23 to 32.67; range, 1.9 to 110 months). The number of cytotoxic regimens prior to bevacizumab treatment did not differ in those that experienced a toxicity versus those that did not (p=0.66). CONCLUSION: The use of bevacizumab in heavily pretreated EOC, FTC, or PPC is worth consideration.

Tumor inflamatorio miofibroblástico peritoneal. Respuesta favorable asociada a infliximab: Caso clínico / Peritoneal myofibroblastic tumor successfully treated with infliximab: Report of one case

Myofibroblastic tumor (MIT) is characterized by the infiltration of different organs, most commonly the lungs, with nodular lesions composed of myofibroblasts and inflammatory cells, which can be identified by specific patterns in the immunohistochemical studies. When it involves the peritoneum it is difficult to eradicate, tends to relapse and it has an invasive behavior, requiring its differentiation from peritoneal carcinomatosis. Treatment may be surgical excision, the use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. We report a 30 years old female with an unremarkable medical history, presenting with abdominal pain and progressive abdominal distention. A CT scan revealed multiple peritoneal nodular lesions. A surgical biopsy was reported as a myofibroblast and inflammatory cell infiltrate. Immunohistochemical staining was consistent with MIT. Given the extensive involvement of the peritoneum surgical therapy was not considered appropriate and treatment with NSAID and glucocorticoids was started. No response was observed after 6 months, therefore infliximab therapy was started. After 10 months of follow-up the patient is well, returned to normal life, ascites improved and resolved and CT scan showed partial regression or stabilization of the lesions.

ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer

PURPOSE: To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status. MATERIALS AND METHODS: One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2x, 1x, and 5x drug concentrations, and the CI values were compared. RESULTS: CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin. CONCLUSION: Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.

Linfangiomatosis mesentérica como causa de abdomen agudo en la tercera edad / Mesenteric lymphangiomathosis presenting as an acute abdomen in an older subject

We report a 71 years old male who consulted in the emergency room for abdominal pain lasting 12 hours. On physical examination there was pain on abdominal palpation and signs of peritoneal irritation. An abdominal CT scan showed a thickening of the medial and distal ileum, multiple adjacent collections and signs of peritonitis. The patient was operated, observing multiple white tumors in the mesentery and serosa of small bowel, one of these lesions, adhered to the bowel wall, had a hemorrhagic infarct. One of the lesions was punctured, obtaining a milky fluid. Biopsies were obtained and the infarcted lesion was excised. The pathological study reported a Mesenteric Multilocular Lymphangioma. The patient had an uneventful postoperative evolution.

Presentamos el caso clínico de un hombre de 71 años, sin antecedentes mórbidos, salvo apendicectomía y colecistectomía hace más de 20 años. Consulta en servicio de urgencias por dolor abdominal de 12 horas de evolución, sin otros síntomas asociados. Al examen físico destacaba dolor abdominal e irritación peritoneal a la palpación de hipocondrio izquierdo. Exámenes destacan aumento de parámetros inflamatorios, Ia tomografía computada de abdomen y pelvis revela engrosamiento de íleon medio-distal, con múltiples colecciones adyacentes y signos de peritonitis. Se realiza laparotomía exploradora, evidenciándose múltiples tumoraciones blanquecinas en mesenterio y serosa de todo el intestino delgado, una de las cuales se aprecia con infarto hemorrágico adherida a Ia pared abdominal. Punción de lesiones da salida a líquido lechoso. Se toman biopsias y se reseca lesión infartada. Paciente evoluciona favorablemente, dado de alta al tercer día. La histología reveló un Linfangioma Quístico Multilocular Mesentérico. Pese a ser una patología infrecuente, debe ser considerada dentro de los diagnósticos diferenciales de abdomen agudo, siendo extremadamente rara su presentación en Ia tercera edad.