Research progress of hyperthermic intraperitoneal chemotherapy in the treatment of colorectal cancer / 国际外科学杂志

Colorectal cancer is a common digestive system malignant tumor in the world, its incidence and mortality rate is in the forefront, with the social progress and the change of diet structure, the incidence of colorectal cancer is gradually increasing, and there is a trend of younger age. Among them, peritoneal metastasis is the main cause of death in patients with colorectal cancer. Non-surgical treatment has been used in the past, but the prognosis is poor. How to treat and prevent peritoneal metastasis in colorectal cancer patients and improve the prognosis of such patients as much as possible is a question worth our in-depth study. The hyperthermic intraperitoneal chemotherapy provides a new direction for the treatment of colorectal cancer patients, usually combined with surgical treatment, and co-applied in the clinic as a new treatment model. This article reviews the treatment mode of hyperthermic intraperitoneal chemotherapy, the choice of drugs, and the progress of research in the treatment and prevention of peritoneal metastasis in colorectal cancer.

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.

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.

Safety evaluation of hyperthermic intraperitoneal chemotherapy in patients with local advanced gastric cancer after radical resection for prevention of peritoneal metastasis / 中华胃肠外科杂志

Objective: Patients with advanced gastric cancer have a poor prognosis and a possibility of peritoneal metastasis even if receiving gastrectomy. Hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively kill free cancer cells or small lesions in the abdominal cavity. At present, preventive HIPEC still lacks safety evaluation in patients with locally advanced gastric cancer. This study aims to explore the safety of radical resection combined with HIPEC in patients with locally advanced gastric cancer. Methods: A descriptive case series study was carried out. Clinicopathological data of 130 patients with locally advanced gastric cancer who underwent radical resection + HIPEC at the Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2020 to February 2021 were retrospectively analyzed. Inclusion criteria: (1) locally advanced gastric adenocarcinoma confirmed by postoperative pathology; (2) no distant metastasis was found before surgery; (3) radical resection; (4) at least one HIPEC treatment was performed. Exclusion criteria: (1) incomplete clinicopathological data; (2) tumor metastasis was found during operation; (3) concomitant with other tumors. HIPEC method: all the patients received the first HIPEC immediately after D2 radical resection, and returned to the ward after waking up from anesthesia; the second and the third HIPEC were carried out according to the patient's postoperative recovery and tolerance; interval between two HIPEC treatments was 48 h. Observation indicators: (1) basic information, including gender, age, body mass index, etc.; (2) treatment status; (3) perioperative adverse events: based on the standard of common adverse events published by the US Department of Health and Public Health (CTCAE 5.0), the adverse events of grade 2 and above during the treatment period were recorded, including hypoalbuminemia, bone marrow cell reduction, wound complications, abdominal infection, lung infection, gastroparesis, anemia, postoperative bleeding, anastomotic leakage, intestinal obstruction, pleural effusion, abdominal distension, impaired liver function, and finally a senior professional title chief physician reviewed the above adverse events and made a safety evaluation of the patient; (4) association between times of HIPEC treatment and adverse events in perioperative period; (5) analysis of risk factors for adverse events in perioperative period. Results: Among the 130 patients, 79 were males and 51 were females with a median age of 59 (54, 66) years and an average body mass index of (23.9±7.4) kg/m(2). The tumor size was (5.4±3.0) cm and 100 patients (76.9%) had nerve invasion. All the 130 patients received radical resection + HIPEC and 125 (96.2%) patients underwent laparoscopic surgery. The mean operative time was (345.6±52.3) min and intraoperative blood loss was (82.0±36.5) ml. One HIPEC treatment was performed in 54 patients (41.5%), 2 HIPEC treatments were in 57 (43.8%), and 3 HIPEC treatments were in 19 (14.6%). The average postoperative hospital stay was (13.1±7.5) d. A total of 57 patients (43.8%) had 71 cases of postoperative complications of different degrees. Among them, the incidence of hypoalbuminemia was 22.3% (29/130), and the grade 2 and above anemia was 15.4% (20/130), lung infection was 3.8% (5/130), bone marrow cell suppression was 3.7% (4/130), abdominal cavity infection was 2.3% (3/130), and liver damage was 2.3% (3/130), wound complications was 1.5% (2/130), abdominal distension was 1.5% (2/130), anastomotic leakage was 0.8% (1/130), gastroparesis was 0.8% (1/130) and intestinal obstruction was 0.8% (1/130), etc. These adverse events were all improved by conservative treatments. There were no statistically significant differences in the incidence of adverse events during the perioperative period among patients undergoing 1, 2, and 3 times of HIPEC treatments (all P>0.05). Univariate and multivariate logistic analyses showed that age > 60 years (OR: 2.346, 95%CI: 1.069-5.150, P=0.034) and neurological invasion (OR: 2.992, 95%CI: 1.050-8.523, P=0.040) were independent risk factors for adverse events in locally advanced gastric cancer patients undergoing radical resection+HIPEC (both P<0.05). Conclusions: Radical surgery + HIPEC does not significantly increase the incidence of perioperative complications in patients with advanced gastric cancer. The age >60 years and nerve invasion are independent risk factors for adverse events in these patients.

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.

Expression of Heat Shock Protein 105b in Adenocarcinoma of Esophagogastric Junction and Its Relation with Effect of Hyperthermic Intraperitoneal Chemotherapy / 肿瘤防治研究

Objective To explore the expression of heat shock protein (HSP) 105b in advanced adenocarcinoma of esophagogastric junction (AEG) patients and its relation with clinicopathological characteristics and effect of hyperthermic intraperitoneal chemotherapy (HIPEC). Methods We randomly divided 166 cases of advanced AEG who underwent open radical gastrectomy and lymphadenectomy D2 compartment into treatment group (prophylactic HIPEC of paclitaxel after operation) and control group (conventional treatment). Immunohistochemistry was used to detect HSP105b expression in postoperative tumor tissues, and to analyze its relation with clinicopathological characteristics and effect of HIPEC. Results The expression of HSP105b was only associated with tumor vein infiltration (t=4.002, P=0.045). The 3-year disease-free survival rate of the patients with high HSP105b expression was significantly lower than those with low HSP105b expression (56.5% vs. 64.8%, χ2=35.508, P < 0.001), and the disease-free survival rate of the patients with high HSP105b expression in treatment group was significantly lower than that with low HSP105b expression (60.7% vs. 71.5%, χ2=77.459, P < 0.001). Conclusion HSP105b can be used as a prognostic factor and its expression can predict the efficacy of HIPEC in the patients with advanced AEG.

Current Situation of Hyperthermic Intraperitoneal Chemotherapy in Peritoneal Carcinoma / 肿瘤防治研究

Peritoneal carcinoma is a kind of malignant tumor which occurs and develops on the peritoneum, including primary and secondary tumors. Hyperthermic intraperitoneal chemotherapy is a combined therapy of intraperitoneal perfusion, hyperthermia and chemotherapy on peritoneal cancer, with satisfactory curative effect. In recent years, with the continuous progress of technology and research, hyperthermic intraperitoneal chemotherapy has become the most effective method for the treatment of peritoneal cancer. In this paper, we review the current situation of hyperthermic intraperitoneal chemotherapy on peritoneal cancer.

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.

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.

Mesotelioma peritoneal multiquístico benigno: reporte de un caso y revisión de la literatura / Benign multicystic peritoneal mesothelioma: case report and literature review

INTRODUCCIÓN: El mesotelioma peritoneal multiquístico benigno (MPMB) es una entidad con muy baja incidencia que se presentan con mayor frecuencia en mujeres jóvenes. CASO CLÍNICO: Paciente de 17 años que consulta por amenorrea secundaria. Además, refería pérdida de peso, estreñimiento y molestias abdominales. La exploración fue normal y en las pruebas de imagen se objetivó una pelvis ocupada por una masa multiquística, de unos 20 cm de diámetro máximo, de paredes finas y contenido anecoico. Se solicitaron marcadores tumorales de los cuales sólo se encontró elevado el CA 19.9 (35,2 U/mL). Se decidió realizar una laparoscopia exploradora para establecer un diagnóstico y ante los hallazgos y al considerarse la masa fácilmente resecable, en el mismo acto quirúrgico se extirpó por completo para su estudio anatomopatológico, que confirmó un MPMB. Se desestimaron tratamientos adicionales y actualmente se encuentra en seguimiento y asintomática. CONCLUSIÓN: La patogénesis del MPMB no está clara. Algunos autores defienden que se trata de una reacción peritoneal a un daño inflamatorio, otros apoyan que se trata de una neoplasia benigna. Esta naturaleza incierta, junto con la escasa experiencia, hacen que el manejo resulte complejo. Es necesario individualizar cada caso e intentar ser conservadores especialmente en pacientes jóvenes. Si se opta por un manejo activo, lo más acertado es la citorreducción completa seguida de quimioterapia hipertérmica peritoneal. El seguimiento, en cualquier caso, debe ser exhaustivo y multidisciplinar principalmente con pruebas de imagen.

BACKGROUND: Benign Multicystic Peritoneal Mesothelioma (BMPM) is an entity with a very low incidence that occurs more frequently in young women. CASE REPORT: A 17-year-old woman attended for secondary amenorrhea. She also referred to weight loss, constipation and abdominal discomfort. The examination was normal and echography revealed a pelvis occupied by a 20 centimeters multicystic mass, with thin walls and anechoic content. A preoperative study with tumor markers was requested in which only a CA 19.9 elevation was observed (35.2 U/ml 0-27). It was decided to perform an exploratory laparoscopy to establish a diagnosis. Due to the findings and because of the fact that the mass was considered easy to remove, it was completely removed in the same surgical act. The pathological result confirmed a BMPM. Additional treatments have been dismissed and are the patient is currently being followed up without symptoms. CONCLUSION: The pathogenesis of BMPM is unclear. Some authors argue that it is a peritoneal reaction to inflammatory damage, others support that it is a benign neoplasm. This uncertain nature coupled with limited experience make management complex. It is necessary to evaluate each case and try to be conservative especially in young patients. If surgery management is chosen, complete cytoreduction followed by hyperthermic peritoneal chemotherapy is the most successful option. The follow-up in any case must be exhaustive and multidisciplinary, mainly with imaging tests.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei: a single-center experience with 854 patients / 中国肿瘤临床

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is gradually being accepted as the standard treatment for PMP. At Aerospace Hospital, we have been treating patients with PMP since 2008 and performing total peritoneal resection since 2016. This study summarizes the experience at our center and collates past data. Methods: We performed a retrospective analysis of a prospectively maintained database of all patients who had undergone CRS and HIPEC for PMP at our center. Clinical data, such as the surgical approach, completeness of cytoreduction, and surgical complications, were collected. The results from follow-up were analyzed to simultaneously evaluate the clinical value of CRS+HIPEC and peritonectomy procedures. Results: A total of 854 consecutive patients with PMP were included in the study. Their mean age was 50 years. The median modified peritoneal cancer index (PCI) was 29. Of the patients, 25.5% under-

Clinical efficacy of hyperthermic intraperitoneal chemotherapy plus cytoreductive surgery for peritoneal metastasis of gallbladder cancer / 中国肿瘤临床

Objective: To investigate the clinical efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) for gallbladder cancer with peritoneal metastasis. Methods: Data of 84 patients, who were admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from January 2015 to January 2018, were retrospectively analyzed. Of the total patients, 31 received HIPEC combined with cytoreductive surgery (CRS) plus postoperative systemic chemotherapy one month after surgery as the study group (Group A), and the other 53 underwent CRS plus postoperative systemic chemotherapy one momth after surgery as the control group (Group B). The clinical effects and adverse reactions in the two groups were observed and compared. Results: The median survival time in the Group A was (21.72±2.96) months, significantly longer than that of (14.93±2.09) months in Group B (P0.05). Conclusions: HIPEC has significant clinical efficacy for gallbladder cancer with peritoneal metastasis. HIPEC can prolong the survival time and have less side effects.

Prognostic analysis of intraoperative chemohyperthermic peritoneal perfusion in patients with advanced gastric cancer of different pathological types and Borrmann's classifications / 中国肿瘤临床

Objective: To understand the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) on prognosis of patients with locally advanced gastric cancer, this study retrospectively analyzed the clinical and pathological data of patients undergoing surgery combined with HIPEC and those undergoing surgery alone. Methods: We retrospectively analyzed 80 stage IIIb gastric cancer patients who underwent HIPEC and 90 stage IIIb gastric cancer patients who underwent surgery alone at Tianjin Medical University Cancer Institute and Hospital between January 2009 and January 2014. These patients were divided into the HIPEC group (study group) and the surgery group (control group). The study and control groups included 24 and 26 signet ring cell carcinoma patients and 56 and 64 non-signet ring cell carcinoma patients, respectively. The study and control groups included 12 and 15 Borrmann type I cases, 28 and 30 Borrmann type Ⅱ cases, 23 and 26 Borrmann type III cases, and 17 and 19 Borrmann type cases, respectively. Four weeks after surgery, the two groups were treated with chemotherapy using the S-1 and oxaliplatin (SOX) regimen for 8 courses. This study analyzed and compared the survival of patients with gastric cancer of different pathological types and Borrmann's classifications. The surgical complications of the two groups were retrospectively analyzed. Results: The 5-year survival rates of the study group and the control group were 36.25% and 28.89%, respectively, and the difference was statistically significant (P0.05). The 5-year survival rates between Borrmann type I and typeⅡ patients in the study and control groups were not significantly different (41.67% vs. 40.00%, 35.71% vs. 33.33%, respectively, P>0.05). There was a statistically significant difference in the 5-year survival rates between Borrmann type III and type patients in the study and control groups (39.13% vs. 26.92%, 29.41% vs. 15.79%, respectively, P0.05). Conclusions: Surgery combined with HIPEC is safe and improves the 5-year survival rate of patients with advanced gastric cancer classified as signet ring cell carcinoma, Borrmann type III, and Borrmann type .

Selection strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy among patients with gastric cancer with peritoneal metastasis / 中国肿瘤临床

Objective: To construct a predictive model to assess the completeness of cytoreduction (CC) and help guiding selection for cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) in patients with gastric cancer with peritoneal metastasis (GCPM). Methods: GCPM patients treated with CRS+HIPEC at Beijing Shijitan Hospital were enrolled in this study. The major clinicopathologic and therapeutic characteristics were compared between those with complete CRS (CCRS) and incomplete CRS (ICRS). A nomogram based on a Logistic regression model was constructed for predicting the risk of ICRS. The nomogram was evaluated using area under receiver operating characteristic curve (AUC) and validated using the bootstrap resampling method. The probability of CCRS was predicted using the nomogram. Results: Among the included 125 patients with GCPM, 52 had CC0 cytoreduction and 73 had CC1-3 cytoreduction. The median overall survival (mOS) was 30.0 (95% CI: 16.8-43.3) months in the CC0 group, which was significantly longer than the mOS of 7.3 (95% CI: 5.8-8.8) months in the CC1-3 group (P<0.001). As there were no significant differences in OS among the CC1, CC2, and CC3 groups, CC0 patients were included in the CCRS group and CC1-3 patients were included in the ICRS group. Multivariate Logistic regression demonstrated that the time of peritoneal metastasis development (OR=14, 95% CI: 2.0-97.9, P= 0.008), preoperative tumor markers (TM) (OR=6.5, 95% CI: 2.1-37.8, P=0.037), and peritoneal cancer index (PCI) (OR=1.5, 95% CI: 1.3-1.8, P<0.001) were independent predictive factors for ICRS. The AUC of the nomogram was 0.985. Internal validation displayed good accuracy and consistency between the predictions and the actual observations. The cutoffs of PCI, with the probability of CCRS set at ≥ 50%, were ≤16, ≤12, ≤10, and ≤5 for synchronous GCPM with normal TM, synchronous GCPM with abnormal TM, metachronous GCPM with normal TM, and metachronous GCPM with abnormal TM, respectively. Conclusions: Complete CRS+HIPEC improves the survival of some patients with GCPM. A selection strategy based on PCI combined with the time of peritoneal metastasis development and TM may be a practical way for selecting patients with GCPM eligible for CCRS.

Influence of warming needling technique on gastrointestinal reaction after hyperthermic intrape-ritoneal chemotherapy in patients with postoperation of colon cancer / 针刺研究

OBJECTIVE: To observe the effect of warming needling therapy on gastrointestinal reaction after hyperthermic intraperitoneal chemotherapy (HIPEC) in patients of spleen and stomach deficiency syndrome after colon cancer surgery. METHODS: A total of 120 cases of HIPEC were randomized into observation group and control group, 60 cases in each. The patients of the two groups all received HIPEC. In the observation group, 1 h before HIPEC, warming needling technique was applied to Zusanli (ST36), Sanyinjiao (SP6) and Yinlingquan (SP9) and the even-needing technique of acupuncture was applied to Neiguan (PC6) for 30 min, and then the intravenous injection with Ondansetron was given 30 min before HIPEC. In the control group, The intravenous injection with Ondansetron was given 30 min before HIPEC. In the two groups, the changes in nausea, vomiting, abdominal distention, diarrhea, total bilirubin (TB), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and KPS score, as well as the average hospitalization length of stay were observed. RESULTS: The total effective rates in the treatment of nausea, vomiting, abdominal distention and diarrhea were 91.67%(55/60), 93.33%(56/60), 80.00%(48/60) and 88.33%(53/60) in the observation group and were 78.33%(47/60), 78.33%(47/60), 63.33%(38/60) and 70.00%(42/60) in the control group respectively, and the total effective rate in the treatment of gastrointestinal reaction of HIPEC in the observation group was obviously higher than that in the control group(P0.05). CONCLUSION: The warming needling technique of acupuncture and moxibustion alleviates the gastrointestinal reaction, improves KPS score and reduces the hospitalization length of stay in HIPEC patients after the surgery of colon cancer and differentiated as the spleen and stomach deficiency in traditional Chinese medicine.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in management of peritoneal carcinomatosis: Single center experience in Korea

PURPOSE: Peritoneal carcinomatosis (PC) has been considered a terminal condition and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIEPC) is regarded as an alternative therapeutic option. This study aimed to evaluate the 30-day clinical outcomes of CRS/HIPEC and the feasibility of the surgery by investigating the morbidity and mortality in Inje University Hospital.METHODS: Data were retrospectively collected from 19 patients with PC who underwent CRS/HIPEC at Inje University Hospital in 2018. We evaluated pre-, intra-operative parameters and postoperative clinical outcomes and early complications.RESULTS: The mean operating time was 506.95 minutes and the mean blood loss was 837.11 mL. Six cases (31.58%) had morbidity of grade III or above. A longer operating time (≥560 minutes, P=0.038) and large blood loss (≥700 mL, P=0.060) were positively correlated with grade III or worse postoperative complications.CONCLUSION: Our early experience with CRS/HIPEC resulted in a 31.58% morbidity rate of grade III and above, with risk factors being longer operating time and greater intraoperative blood loss. As the surgical team's skills improve, a shorter operating time with less intraoperative blood loss could result in better short-term outcomes of CRS/HIPEC.

Incorporation of paclitaxel-based hyperthermic intraperitoneal chemotherapy in patients with advanced-stage ovarian cancer treated with neoadjuvant chemotherapy followed by interval debulking surgery: a protocol-based pilot study / 부인종양

OBJECTIVES: We conducted a protocol-based cohort study to evaluate the outcomes of interval debulking surgery (IDS) followed by paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of advanced-stage ovarian cancer. METHODS: From October 2015 to May 2018, 65 patients with stages IIIC–IV ovarian cancer were treated according to the study protocol. HIPEC was performed with paclitaxel (175 mg/m2) for 90 minutes, only in cases of optimal cytoreduction. RESULTS: Of 65 patients, 40 (61.5%) patients underwent neoadjuvant chemotherapy (NAC), 34 (52.3%) patients had a high tumor burden with a Fagotti score ≥8 at diagnostic laparoscopy, and 6 (9.2%) had definite stage IV metastasis and/or poor performance status before NAC. Twenty-seven (41.5%) patients underwent IDS followed by HIPEC. The mean duration of IDS with HIPEC was 543.8 (range, 277.0–915.0) minutes. Grade III/IV perioperative complications occurred in 7.4% (n=2)/3.7% (n=1) of patients and no cases of mortality were reported within 30 days postoperatively. The median progression-free survival was 21.3 months, and the median overall survival was not reached for those who received HIPEC. CONCLUSIONS: According to our study protocol, IDS followed by paclitaxel-based HIPEC as a first-line treatment appears to be feasible and safe for the treatment of advanced-stage ovarian cancer. Further evaluations of this procedure are required to assess its survival benefits.