Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

Predictors of recurrence of peritoneal carcinomatosis among patients with colorectal cancer following cytoreductive surgery alone versus cytoreductive surgery plus HIPEC

Background: Peritoneal carcinomatosis (PC) is a lethal regional progression in patients with colorectal cancer (CRC). Treatment with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves better local control than systemic palliative chemotherapy. Objectives: To assess the efficacy on the prognosis of CRS and HIPEC compared with CRS only and to identify possible clinicopathological factors associated with the recurrence of PC. Methods: The present retrospective study included all colorectal carcinoma cases with PC subjected to CRS with or without HIPC from January 2009 to June 2018 at the National Cancer Institute (NCI), Cairo University, Cairo, Egypt. The outcome is evaluated in terms of recurrence-free survival (RFS) and its predictors. Results: Out of the 61 patients, 45 patients (73.8%) underwent CRS plus HIPEC, and 16 (26.2%) underwent CRS alone. The 1-year RFS was 55.7%, with a median of 12 months. The risk factors for recurrence identified in the univariate analysis were T4 primary tumor, high-grade, positive lymphovascular invasion (LVI), positive extracapsular nodal spread, and patients treated with CRS only, without HIPEC. In the multivariate analysis, the independent risk factors for recurrence were high grade and patients treated with CRS only. Conclusion: T4 primary tumor, high grade, positive LVI, and positive extracapsular nodal spread seemed to be important predictors of recurrence following the treatment of PC. Our study also demonstrated that the addition of HIPEC to CRS improved the RFS. (AU)

A phase 2 trial of short-course Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) at interval cytoreductive surgery (iCRS) for advanced ovarian cancer / Quimioterapia Intraperitoneal Hipertérmica (HIPEC) de curta duração ao tempo da cirurgia citorredutora de intervalo (iCRS) para câncer de ovário avançado: ensaio clínico de fase 2

ABSTRACT Objective: to report the final analysis of a phase 2 trial assessing the efficacy and safety of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with advanced epithelial ovarian cancer (EOC). Methods: this was an open-label, multicenter, single-arm trial of HIPEC in patients with advanced EOC who underwent interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy (NACT). HIPEC was performed as a concentration-based regimen of platinum-based chemotherapy for 30 minutes. Primary endpoint was the rate of disease progression occurring at nine months following iCRS plus HIPEC (PD9). Secondary endpoints were postoperative complications, time to start adjuvant chemotherapy, length of hospital and ICU stay, quality of life (QoL) over treatment, and ultimately 2-year progression-free survival (PFS) and overall survival (OS). Analysis was by intention-to-treat with final database lock for survival outcomes on February 23, 2021. Results: fifteen patients with stage III EOC were enrolled between February 2015 and July 2019, in four centers. The intention to treat PD9 was 6.7%. With a median follow-up of 33 months (IQR, 24.3-46.5), the median PFS was 18.1 months and corresponding 2-year rates of PFS and OS was 33.3% and 93.3%, respectively. Three patients (20%) experienced graded III complications. Median length of hospital and ICU stay was 5 (IQR, 4-6.5) and 1 (IQR, 1-1) days, respectively. Time to restart systemic chemotherapy was 39 (IQR, 35-49.3) days and no significant difference over time in QoL was observed. Conclusions: we demonstrate preliminary efficacy and safety of short-course HIPEC in patient with advanced EOC.

RESUMO Objetivo: apresentar a análise final de ensaio clínico de fase 2 que avaliou a eficácia e a segurança da quimioterapia intraperitoneal hipertérmica (HIPEC) de curta duração em pacientes com câncer epitelial de ovário avançado (EOC). Métodos: estudo aberto, multicêntrico, de braço único avaliando a HIPEC em pacientes com EOC avançado submetidos a cirurgia citorredutora de intervalo (iCRS) após quimioterapia neoadjuvante (NACT). A HIPEC foi realizada como regime baseado na concentração de cisplatina, perfundida por 30 minutos. O desfecho primário foi a taxa de progressão da doença 9 meses após a iCRS com HIPEC (PD9). Os desfechos secundários foram complicações pós-operatórias, tempo para iniciar a quimioterapia adjuvante, tempo de internação e permanência em UTI, qualidade de vida (QoL) ao longo do tratamento e, finalmente, sobrevida cumulativa livre de progressão (PSF) e global (OS) em 2 anos. As análises foram em intenção de tratar (ITT) com fechamento dos dados para análise da sobrevida em 23 de fevereiro de 2021. Resultados: quinze pacientes com EOC em estágio III foram incluídos no estudo entre fevereiro de 2015 e julho de 2019 em quatro centros recrutadores. A PD9 por ITT foi de 6,7%. Com acompanhamento mediano de 33 meses (IQR, 24,3-46,5), a PFS mediana foi de 18,1 meses e as taxas correspondentes de PFS e OS em 2 anos foram 33,3% e 93,3%, respectivamente. Três pacientes (20%) apresentaram complicações grau III. O tempo mediano de internamento hospitalar e em UTI foi de 5 (IQR, 4-6,5) e 1 (IQR, 1-1) dias, respectivamente. O tempo para reinício da quimioterapia sistêmica foi de 39 dias (IQR, 35-49,3) e não foi observada diferença significativa na QoL ao longo do tratamento. Conclusões: demonstrou-se eficácia e segurança preliminares da HIPEC de curta duração em pacientes com EOC avançado.

Cirurgia Citorredutora com Quimioterapia Intraperitoneal Hipertérmica em Pacientes com Adenocarcinoma Mucinoso de Apêndice: Série de 43 Casos / Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy in Patients with Appendix Mucinous Adenocarcinoma: Series of 43 Casess / Cirugía Citorreductiva con Quimioterapia Intraperitoneal Hipertermal en Pacientes con Adenocarcinoma Mucinoso de Apéndice: Serie de 43 Caso

Introdução: O carcinoma primário de apêndice é uma condição rara. Muitas revisões retrospectivas internacionais delineiam a experiência de diferentes centros em neoplasias apendiculares. Por sua vez, o tratamento do câncer nessa localização é complexo e depende do subtipo histológico e da extensão da doença. Um dos tratamentos mais promissores é a cirurgia citorredutora (CCR) associada à quimioterapia intraperitoneal hipertérmica (HIPEC). No Brasil, não há descrição de séries de casos que tiveram essa abordagem terapêutica. O objetivo desta série de casos é analisar as características sociodemográficas e o tipo de intervenção terapêutica em pacientes com doenças malignas de apêndice em um Centro de Assistência de Alta Complexidade em Oncologia III (Cacon III). Relato dos casos: Foram incluídos 43 casos de tumores primários de apêndice. O adenocarcinoma do apêndice do tipo mucinoso de baixo grau foi a neoplasia mais diagnosticada. O principal protocolo utilizado foi de uma a duas cirurgias e aplicação de mitomicina C em temperatura média de 40 graus. Os casos apresentaram grande heterogeneidade quanto ao uso do protocolo. Conclusão: O presente relato de 43 casos é importante por se tratar de um tumor raro nessa localização. A modalidade terapêutica descrita é promissora, mas não há protocolo definido para essa finalidade. É necessário atualizar as diretrizes terapêuticas para normatizar a conduta internamente, especialmente em se tratando de uma unidade de referência nacional

Introduction: Primary appendix carcinoma is a rare condition. Many international retrospective reviews outline the experience of different centers in appendicular neoplasms. The cancer treatment in this location is complex and depends on the histological subtype and the extent of the disease. One of the most promising treatments is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In Brazil, there is no description of series of cases with this therapeutic approach. The purpose of this case series is to analyze the sociodemographic characteristics and the type of therapeutic intervention in patients with malignant diseases of the appendix in a High Complexity Care Center in Oncology III (Cacon III). Case reports: 43 cases of primary appendix tumors were included. Low-grade mucinous adenocarcinoma was the most diagnosed neoplasm. The main protocol used was 1 to 2 surgeries and application of mitomycin C at an average temperature of 40 degrees. There was great heterogeneity regarding the use of the protocol. Conclusion: The present report of 43 cases is important because it is a rare tumor with this location. The therapeutic modality described is promising, but there is no defined protocol for this purpose. It is necessary to update the therapeutic guidelines to standardize the conduct internally, especially in the case of a national reference unit

Introducción: El carcinoma primario de apéndice es una entidad poco frecuente. Numerosas revisiones retrospectivas internacionales describen la experiencia de diferentes centros en neoplasias apendiculares. A su vez, el tratamiento de esta localización del cáncer es complejo y depende del subtipo histológico y la extensión de la enfermedad. Uno de los tratamientos más prometedores es la cirugía citorreductora (CCR) asociada a quimioterapia intraperitoneal hipertérmica (HIPEC). En Brasil, no hay descripción de series de casos que tuvieran este abordaje terapéutico. El propósito de esta serie de casos es analizar las características sociodemográficas y el tipo de intervención terapéutica en pacientes con enfermedades malignas del apéndice en un Centro Asistencial de Alta Complejidad en Oncología III (Cacón III). Reporte de los casos: Se incluyeron 43 casos de tumores primarios de apéndice. El adenocarcinoma mucinoso de bajo grado tuvo la mayor incidencia. El protocolo principal utilizado fue de una a dos cirugías y aplicación de mitomicina C a una temperatura promedio de 40 grados. Los casos mostraron gran heterogeneidad en cuanto al uso del protocolo. Conclusión: El presente informe es importante porque es un tumor raro. La modalidad terapéutica descrita es prometedora, pero no existe un protocolo definido para tal fin. Es necesario actualizar las pautas terapéuticas para normalizar la conducta internamente, especialmente en el caso de una unidad de referencia nacional

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.

Disseminated intravascular coagulation from Intraperitoneal Oxaliplatin for Appendiceal Carcinoma: A case report

@#This is a case of a 65-year-old female diagnosed with appendiceal carcinoma, who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Profuse bleeding through the peritoneal drains, with hemodynamic instability, warranted a re-exploration on the fourth postoperative day. Intraoperatively, there was 500 mL of blood clots mostly on the right upper quadrant, diffuse muscle oozing along the previously-stripped right hemidiaphragm and right paracolic gutter, and a non-expanding hematoma on the right anterior abdominal wall. Bleeding parameters were checked postoperatively, and derangements pointing to a disseminated intravascular coagulation were noted. The patient was managed with multiple blood transfusions of packed red blood cells, fresh frozen plasma, platelet concentrates, and cryoprecipitate. Dexamethasone and tranexamic acid were given intravenously. The patient was discharged well on postoperative day 14 after clinical resolution of the bleeding. Eight days after discharge, however, patient succumbed to myocardial infarction.

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.

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.

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.

Progress in conversion therapy for stage IV gastric cancer / 中华胃肠外科杂志

Gastric cancer is one of the most common malignancy in China. Most of the patients of gastric cancer treated clinically are in advanced stage. In the past years, with the progress of anti-cancer drug therapy, after the comprehensive treatment based on drugs therapy of inoperative stage IV gastric cancer, some cases can reduce the tumor stage and get the opportunity of radical operation. Some of the patients who underwent surgical treatment can get the chance of long-term survival. The results of REGATTA trial confirmed that palliative surgery plus chemotherapy could not improve the long-term survival of patients with stage IV gastric cancer. Neoadjuvant intraperitoneal plus intravenous chemotherapy can reduce the tumor stage of some cases of stage IV gastric cancer with peritoneal metastasis and receive surgical treatment, so as to gain the chance of long-term survival. Regimen of intraperitoneal hyperthermia chemotherapy combined with PHOENIX trial is expected to improve the conversion operation rate of gastric cancer with peritoneal metastasis. Paclitaxel-based three-drug chemotherapy can reduce the tumor stage of some inoperable advanced gastric cancer and obtain the opportunity of radical operation, improving the disease-free survival rate and overall survival rate of patients, thus has become the cornerstone of conversion therapy for stage IV gastric cancer. Antiangiogenic targeted drug apatinib combined with paclitaxel is safe and reliable, and can be used as an alternative for the conversion therapy of stage IV gastric cancer, which provides a new idea for cytotoxic drugs combined with targeted drugs. In the era of immunotherapy, the combined application and first-line application of immunosuppressive drugs has become a clinical consensus. For advanced Her-2 positive esophagogastric junction adenocarcinoma cases, the successful exploration of the four-drug combination of chemotherapy+ anti-Her-2 targeted drugs+ anti-PD1 monoclonal antibody combined with the first-line therapy has opened up a new era of transformational therapy for stage IV gastric cancer. Gastric cancer is a malignant tumor with high heterogeneity, the classification of stage IV gastric cancer represented by Yoshida classification is based on imaging, and a more reasonable classification method should be developed in combination with gene detection in the future. Based on this, an individualized and accurate conversion therapy plan is formulated, so as to effectively improve the long-term survival of patients with stage IV gastric cancer.