Establishment of treatment center for peritoneal metastasis in colorectal cancer / 中华胃肠外科杂志

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

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.

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.

Manejo del mesotelioma peritoneal maligno con citorreducción quirúrgica más quimioterapia hipertérmica intraperitoneal en el Instituto Nacional de Cancerología, Colombia: reporte de un caso y revisión bibliográfica / Peritoneal malignant mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at the National Cancer Institute, Colombia: case report and literature review

El mesotelioma peritoneal es una neoplasia que se origina en las células mesoteliales del peritoneo. Histórica-mente, la supervivencia de los pacientes con mesotelioma peritoneal maligno sin tratamiento, es menor de 12 meses y se considera una neoplasia resistente a la quimioterapia. La citorreducción quirúrgica y la quimioterapia regional administrada como quimioterapia hipertérmica intraperitoneal (Hyperthermic Intraperitoneal Chemothe-rapy, HIPEC) se asocia con mejor supervivencia a largo plazo.Se presenta el caso de un paciente con antecedentes de exposición al asbesto y con diagnóstico de mesotelioma peritoneal maligno de tipo epitelioide, que fue tratado con cirugía citorreductora más quimioterapia hipertérmica intraperitoneal en el Instituto Nacional de Cancerología con una supervivencia de un año libre de enfermedad

Peritoneal mesothelioma is originated at the mesothelial cells of the peritoneum. Historically the survival of patients with this disease is less than 12 months without treatment and it is considered a neoplasm resistant to chemotherapy. Citorreductive surgery with hiperthermic intraperitoneal chemotherapy (HIPEC) is associated with an increased long-term survival. Here we present the case of a patient who had a past history of asbestos exposure and who was diagnosed with peritoneal mesothelioma of the epithelioid subtype. The patient was treated with cytoreductive surgery and HIPEC at the Instituto Nacional de Cancerología (Bogotá, Colombia) and has had a 12 month disease free survival

High-dose versus Low-dose 5-Fluorouracil and Cisplatin Based Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma

BACKGROUND/AIMS: Hepatic arterial infusion chemotherapy (HAIC) has been reported as an effective treatment for advanced hepatocellular carcinoma. The aim of this study is to compare the effect and safety between a high-dose regimen (750 mg/m2 5-fluorouracil [FU] and 25 mg/m2 cisplatin on day 1–4) and a low-dose regimen (500 mg/m2 5-FU on day 1–3 with 60 mg/m2 cisplatin on day 2). METHODS: A total of 48 patients undergoing HAIC were retrospectively analyzed. Thirty-two patients were treated with the high-dose and 16 patients with the low-dose regimen. RESULTS: Complete response (CR), partial response (PR), stable disease (SD), and progressive disease were noted in one (3.1%), 15 (46.9%), three (9.4%), and 13 patients (40.6%) in the highdose group, and 0 (0%), one (6.3%), eight (50%), and seven patients (43.8%) in the low-dose group (P=0.002). The disease control rate (CR, PR, and SD) did not differ between groups (59.4% vs. 56.3%, P=1.000), but the objective response rate (CR and PR) was significantly higher in the high-dose group (50.0% vs. 6.3%, P=0.003). The median progression free survival did not differ between groups (4.0 vs. 6.0, P=0.734), but overall survival was significantly longer in the high-dose group (not reached vs. 16.0, P=0.028). Fourteen (43.8%) patients in the high-dose group and two patients (12.5%) in the low-dose group experienced grade 3–4 toxicities (P=0.050). CONCLUSIONS: High dose HAIC may achieve better tumor response and may improve overall survival compared to a low-dose regimen. However, the high-dose regimen should be administered cautiously because of the higher incidence of adverse events.

Cirurgia citorredutora e quimioterapia intraperitoneal hipertérmica no tratamento primário dos tumores epiteliais de ovário: projeto terapêutico piloto para pacientes do SUS/PE / Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of epithelial ovarian cancer: a therapeutic pilot study for patients from SUS/PE

Contexto: O câncer ovariano representa a mais letal das neoplasias ginecológicas. Dada a predileção pela via peritoneal na disseminação desta neoplasia maligna (i.e.: carcinomatose peritoneal), a utilização de quimioterapia intraperitoneal hipertérmica (i.e.: HIPEC ­ hyperthermic intraperitoneal chemotherapy; sigla mantida em inglês) representa promissora opção de tratamento para seu manejo multidisciplinar. Assim, a adoção de um protocolo simplificado de HIPEC poderia incrementar os resultados de seu tratamento às custas de reduzida morbimortalidade. Objetivos: Avaliar a eficácia e a segurança de um protocolo de HIPEC para tratamento do câncer epitelial avançado de ovário em pacientes da rede pública de saúde ­ SUS, em Pernambuco. Métodos: Estudo transversal (análise interina) de dados oriundos de ensaio clínico prospectivo fase II, de braço único e aberta, ainda em curso. O protocolo em estudo envolve o tratamento multidisciplinar do câncer de ovário com quimioterapia sistêmica perioperatória (i.e.: neoadjuvante e adjuvante) associado à citorredução ciurgica com HIPEC. O protocolo de HIPEC utilizou o dispositivo Performer HT (RanD S.r.l., Medolla ­ MO, Itália) e envolveu o uso de cisplatina (25mg/m²/L) perfundida em solução glicosada de diálise peritoneal por 30 minutos, sob temperatura de 41 a 43°C. O estudo foi aprovado pela CONEP (CAAE: 04016212.5.0000.5201) e registrado no ClinicalTrial.gov (NCT02249013). Recebeu financiamento do Decit/SCTIE/MS ­ CNPq/FACEPE/SES-PE (APQ:0187-4.01/13) e do FAPE/IMIP. Resultados: Entre março de 2015 e junho de 2017 foram realizados nove procedimentos de HIPEC em nove pacientes portadoras de neoplasia epitelial de ovário em estádio FIGO IIIB (n=1) ou IIIC (n=8), dos sub-tipos histológicos endometrióide (n=1) e seroso (n=7) e misto (n=1), e com idade mediana foi de 43 (Min ­ Max: 19 ­ 63) anos. O valor mediano do marcador tumoral CA125 antes do início do tratamento foi de 692U/mL (Min ­ Max: 223,7 ­ 6550), o qual foi reduzido para 35,78U/mL (Min ­ Max: 18,5 ­ 374,6) após tratamento sistêmico com 3 (Min ­ Max: 2 ­ 4) ciclos de quimioterapia neoadjuvante baseada em platina, o que resultou em PCI (i.e.: índice de disseminação peritoneal) de 9 (Min ­ Max: 3 ­ 18) ao tempo do procedimento de HIPEC, realizado após 29 dias (Min ­ Max: 26 ­ 43) do último ciclo de quimioterapia pré-operatória. Oito procedimentos de citorredução associada à HIPEC resultaram em citorredução macroscópica completa, isto às custas de ressecção colônica em três pacientes ­ exenteração pélvica posterior (n=2) e colectomia parcial (n=1). O com tempo cirúrgico mediano foi de 395 minutos (Min ­ Max: 235­760), com tempo mediano de internamento hospitalar de 4 dias (Min ­ Max: 3 ­ 10). Todos os pacientes deixaram a UTI na manhã seguinte aos procedimentos, ao passo que 91% das morbidades compreenderam complicações menores grau I e II, de acordo com a classificação de Clavien-Dindo. Segundo a Common Terminology Criteria for Adverse Events ­ Versão 4 (CTCAE v4.03), as complicações mais comuns foram vômitos G1/G2 (n=2) e anemia G3 (n=2). Apenas uma paciente requereu re-operação ao quarto dia de pós-operatório devido hemorragia intraperitoneal sem foco de sangramento específico (complicação grau IIIB) e não houve registro de óbitos ou complicações tardias relacionadas aos procedimentos. O tempo mediano para reinício do tratamento sistêmico foi de 37 dias (Min ­ Max: 33 ­ 50) e todas as pacientes completaram tratamento sistêmico previsto no protocolo do estudo (i.e.: 6 ciclos de quimioterapia). Conclusões: Este protocolo de tratamento multidisciplinar parece ser factível e seus dados preliminares apontam para curto tempo de internação e baixa morbidade. Este é um ensaio clínico pioneiro no Brasil e também o primeiro a usar o dispositivo Performer HT

Context: Ovarian cancer is the main lethal gynecologic malignance. Due to its predilection for peritoneal route of spreading (i.e.: peritoneal carcinomatosis), the use of HIPEC-Hyperthermic Intraperitoneal Chemotherapy emerged as a promising treatment option for the comprehensive management of this malignancy. Thus, the adoption of a simplified protocol of HIPEC could increase the results of treatment with reduced morbidity and mortality. Objectives: To evaluate the efficacy and safety of a HIPEC protocol for treatment of advanced epithelial ovarian cancer patients from the Public Health System ­ SUS in Pernambuco. Methods: A cross-sectional study (interim analysis) was carried out on the women enrolled in our ongoing single-arm, open label, phase 2 clinical trial. The study involved the multidisciplinary treatment with perioperative systemic chemotherapy associated cytoreductive surgery (CRS) plus HIPEC. The HIPEC protocol used Performer HT device (RAND Srl, Medolla - MO, Italy) and involved the use of cisplatin (25mg/m²/L) perfused into dextrose peritoneal dialysis for 30 minutes under temperature of 41-43°C. The study was approved by CONEP (CAAE: 04016212.5.0000.5201) and recorded in ClinicalTrial.gov (NCT02249013). It received funding from Decit/SCTIE/MS - CNPq/FACEPE/SES-PE (APQ: 0187-4.01/13) and FAPE/IMIP. Results: From March 2015 to August 2016, nine patients with stage IIIB (n=1) or IIIC (n=8) epithelial ovarian carcinoma were enrolled into our trial, with sub-types endometrioid (n=1), serous (n=7) or mixed (n=1) adenocarcinoma, and median (range) age of 43 years (range: 19 ­ 63). The median preoperative serum CA125 levels at diagnosis was 692U/mL (range: 223.7­6550), which was reduced to 35.78U/mL (Min ­ Max: 18,5 ­ 374,6) after a median of 3 (range: 2 ­ 4) cycles of neoadjuvant chemotherapy, and peritoneal cancer index scores (PCI) of 9 (range: 3 ­ 18) at the time of CRS/HIPEC, developed after 29 days (range: 26 ­ 43) from the last neoadjuvant course of chemotherapy. Eight procedures resulted in no visible disease, and three patients required bowel resection as rectosigmoidectomy (n=2) or partial colectomy (n=1). Median operation time was 395 minutes (range: 235 ­ 760), with a length of hospital stay of 4 days (range: 3­10). All patients left the ICU on the morning after the procedure, whereas about 91% of postoperative complications were minor grade I and II complications, according to the Clavien­Dindo classification. The most common morbidities were minor G1/G2 vomiting (n=2) and G3 anemia (n=2), according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI/CTCAE) classification version 4.0. Only one patient experienced reoperation at the fourth postoperative day because of G3 postoperative hemorrhage, but no deaths or long-term complications were recorded. Time to re-starts systemic chemotherapy (i.e.: adjuvant chemotherapy) was 37 days (range: 33 ­ 50) and all patients completed the systemic treatment protocol (i.e.: 6 cycles of chemotherapy). Conclusions: Our comprehensive multimodal protocol seems to be feasible and safe, with low rates of complications and a short length of hospital stay in this preliminary report. This is a pioneering clinical trial in Brazil and also the very first to use the Performer HT device

Progress in prophylatic hyperthermic intraperitoneal chemotherapy for advanced gastric carcinoma / 中华胃肠外科杂志

Advanced gastric cancer (AGC) has a high recurrence rate (especially peritoneal relapse) and a poor prognosis. Systematic chemotherapy or targeted therapy have not been able to significantly reduce the major cause of an unfavorable prognosis, namely the high peritoneal AGC recurrence rate post-surgery. Further studies concerning the application of hyperthermic intraperitoneal chemotherapy (HIPEC) post curative surgery for AGC patients, namely the prophylactic HIPEC (P-HIPEC), have involved a prophylactic approach to prevent peritoneal relapse following curative gastrectomy in high-risk patients. Theoretically, breaking the "plasma-peritoneal barrier" increases cytotoxic chemotherapy activity via a synergistic hyperthermic effect; therefore, HIPEC can eradicate free cancer cells and micro-metastasis within the peritoneal cavity intraoperatively or soon after curative gastrectomy to reduce peritoneal recurrence. Many clinical trials have shown that P-HIPEC can reduce peritoneal recurrence and improve prognosis of AGC patients. However, some studies applying HIPEC at an early stage have revealed a high rate of complications that limited generalizability. This procedure has been increasingly adopted, given the complication rate has now been reduced and safety has been proven. Recently, for assessing the important role of HIPEC, many high-quality prospective randomized controlled clinical trials have been conducted to further investigate the best guidance for P-HIPEC and to demonstrate its effectiveness and safety with a higher grade of evidence. With theory development, the technique, equipment, and management of HIPEC and the role of P-HIPEC for AGC continues to evolve. This study summarizes the progress of P-HIPEC for high-risk AGC patients.

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

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

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

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

Segunda citorreducción más quimioterapia hipertérmica intraperitoneal por recaída de seudomixoma peritoneal / Second cytoreduction plus intraperitoneal hyperthermic chemotherapy in recurrence of pseudomyxoma peritonei

Introducción. El seudomixoma peritoneal es una condición rara caracterizada por la presencia de ascitis mucinosa e implantes peritoneales, en la mayoría de los casos, provenientes de tumores mucinosos del apéndice. El tratamiento primario de esta enfermedad es quirúrgico, y la citorreducción más quimioterapia hipertérmica intraperitoneal es el estándar de tratamiento actual, con supervivencia global a 5 y 10 años hasta de 96 y 68 %, respectivamente. No obstante, es una cirugía con alta morbilidad y considerable mortalidad, que apenas se está introduciendo en Colombia y la experiencia es incipiente. El porcentaje de recaída es de 28 a 44 % y existen pocos reportes sobre su manejo; la segunda citorreducción más quimioterapia hipertérmica intraperitoneal parece tener resultados aceptables en cuanto a supervivencia, morbilidad y mortalidad. Resultados. No hay estudios de segundas intervenciones por recaída peritoneal del seudomixoma en Colombia y, por esta razón, se decidió reportar la experiencia de dos casos del Instituto Nacional de Cancerología, donde, después de una primera citorreducción más quimioterapia hipertérmica intraperitoneal, los pacientes presentaron recaída peritoneal diagnosticada con imágenes durante el seguimiento y fueron sometidos a una nueva cirugía con buen resultado quirúrgico. Conclusión. La citorreducción secundaria más quimioterapia hipertérmica intraperitoneal es un procedimiento complejo con morbilidad considerable, que debe practicarse en lugares con experiencia y que proporciona al paciente un tratamiento radical y, posiblemente, se convierta en el manejo estándar de la recaída

Introduction: Peritoneal pseudomyxoma is a rare condition characterized by mucinous ascitis and peritoneal implants, originating from mucinous tumors of the apendix in the majority of cases. Primary treatment is surgical resection, with cytoreduction surgery plus hiperthermic intraperitoneal chemotherapy as the current standard of care, with 96% and 68% 5 and 10 year overall survival rates. Nonetheless, it is a surgical procedure associated with high morbidity and considerable mortality, with initial experience in Colombia. Recurrence is estimated between 28% and 44% and few reports address the management of recurrence peritoneal pseudomyxoma; second cytoreduction surgery plus hiperthermic intraperitoneal chemotherapy (CRS + HIPEC) seems to have acceptable results in terms of survival, morbidity and mortality. No studies of second CRS + HIPEC have been reported in Colombia; this is why we decided to publish two cases treated at the Instituto Nacional de Cancerología, Bogotá, Colombia, who had recurrence after a fist CRS + HIPEC, diagnosed by follow up images and who were taken to a second surgical treatment with good results. Conclusion: Second CRS + HIPEC is a technically challenging procedure with considerable morbidity that should only be performed in specialized and experienced centers, a radical form of treatment that could possibly become the standard of choice for recurrence.

Exploring flow rate selection in HIPEC procedures / Explorando parâmetros de fluxo em procedimentos de HIPEC

ABSTRACT Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a main comprehensive treatment of peritoneal malignancies. However, current data on the literature are very heterogeneous in terms of its technical particularities, which require some efforts to standardization of practices. In these setting, we present some early data from a pioneering clinical trial in Brazil (ClinicalTrials.gov Identifier: NCT02249013) to explore the dynamic relationships between flow rates and temperature parameters in the first cases of our study, which may help in selecting better technical parameters during HIPEC procedures.

RESUMO Cirurgia citorredutora avançada e quimioterapia intraperitoneal hipertérmica (i.e.: HIPEC, sigla em inglês) têm se consagrado como promissora abordagem terapêutica multidisciplinar para neoplasias malignas peritoneais. Contudo, dados da literatura corrente são muito heterogêneos em torno de muitos de seus aspectos técnicos, o que demanda algum esforço na busca por padronizações do procedimento. Neste sentido, são apresentados dados de um ensaio clínico pioneiro no Brasil (ClinicalTrials.gov Identifier: NCT02249013), relacionando parâmetros dinâmicos de taxas de fluxo e temperaturas de perfusão nos primeiros casos do estudo, o que pode ajudar na seleção de melhores parâmetros técnicos para procedimentos de HIPEC.

Study of introperitoneal hyperthermic perfusion chemotherapy combined with systemic neoadjuvent chemotherapy in treatment of gastric cancer patients with peritoneal carcinomatosis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>The aim of this study is to discuss the curative effect of introperitoneal hyperthermic perfusion chemotherapy(IHPC) combined with systemic neoadjuvant chemotherapy on the gastric cancer patients with peritoneal carcinomatosis.</p><p><b>METHODS</b>Sixty-four patients with gastric cancer and peritoneal carcinomatosis who were hospitalized in the Department of Gastrointestinal Surgery of First Hospital of Jilin University from December 2006 to December 2013. After peritoneal carcinomatosis was confirmed during laparoscopic exploration, FOLFOX6 (oxaliplatin and calcium folinate and 5-Fu) was performed for systemic chemotherapy. One course was 14 days and a complete treatment includes four courses. At the same time, patients underwent peritoneal catheter insertion and received IHPC(5-Fu 1 500 mg/m(2) and Cisplatin 35 mg/m(2) were added into 0.9% NaCl solution 2 000 ml, the infusion velocity was 35-45 ml/min, infusion time was 45-60 minutes, the temperature was controlled to 41°C). A comprehensive evaluation was taken after the fourth course of treatment before operation. Further surgical therapy was performed according to the assessment result.</p><p><b>RESULTS</b>Sixty-four patients received IHPC combined with systemic chemotherapy. Thirty-two patients(50.0%) had partial response, 18(28.1%) stable disease, and 14(21.9%) progressive disease after chemotherapy. No severe complications or death occurred during the neoadjuvant chemotherapy. Thirty-two patients(50.0%) received radical resection, 10(15.6%) palliative operation, and another 22 patients(37.4%) didn't comply with inclusion criteria of operation. Patients receiving operation had a median survival time of 678 days, which was significantly longer than patients without operation, with a median survival time of 251(χ(2)=23.34, P=0.02).</p><p><b>CONCLUSIONS</b>IHPC combined with systemic chemotherapy is an effective therapeutic method for gastric cancer patients with peritoneal carcinomatosis in terms of reducing preoperative tumor load and achieving radical resection.</p>

Application study on regional infusion chemotherapy by celiac trunk during operation in advanced gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients.</p><p><b>METHODS</b>One hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups.</p><p><b>RESULTS</b>The baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ=0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ=5.382, P=0.020; 58.4% vs. 34.4%, χ=6.636, P=0.010).</p><p><b>CONCLUSION</b>Regional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.</p>

Initial experience with hyperthermic intra peritoneal chemotherapy and cytoreductivesurgery.

BACKGROUND: Promising results were reported with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal carcinomatosis. Experiences in India are not published. This is a preliminary report. MATERIALS AND METHODS: From eight patients with peritoneal metastasis, six patients (5 M, 1 F), aged (40‑62 years) were treated with CRS and HIPEC between May 2010 and August 2011 from a single institution. Three had Mucinous Adenocarcinoma of Appendix and one each with Mesothelioma, Ovarian Cancer and Colonic Cancer. Four were earlier treated with systemic chemotherapy and recurred. Pre‑operative peritoneal cancer index (PCI) was calculated based on recent computerized tomography or positron emission tomography scans. Surgical completeness cytoreduction score (CCS) was classified as macroscopically complete (CCS‑0); optimal residual disease ≤2.5 mm in any region (CCS‑1); or grossly incomplete: Residual disease >2.5 mm (CCS‑2) or >25 mm (CCS‑3). They were treated by closed perfusion technique with mitomycin‑C (MCC) and cisplatin at 41‑42°C, for 60 min. RESULTS: Optimal cytoreduction (residual tumor nodules <2.5 mm i.e. CC0 and CC1) was performed in four patients (66.67%). There was no operative mortality or Grade 3 and 4 toxicity. Patients with PCI <11 are alive without recurrence with overall survival of 26‑31 months. Those with PCI >11 had recurrence with overall survival of 3‑19 months. Two patients died at 3 and 9 months. CONCLUSION: CRS and HIPEC is a promising therapeutic option in selected patients with peritoneal carcinomatosis. These results in six patients are preliminary but encouraging. Patient with low PCI had better disease free survival.

Postoperative peritonitis without an underlying digestive fistula after complete cytoreductive surgery plus HIPEC

Peritoneal carcinomatosis [PC] is a pernicious event associated with a dismal prognosis. Complete cytoreductive surgery [CCRS] combined with hyperthermic intraperitoneal chemotherapy [HIPEC] is able to yield an important survival benefit but at the price of a risky procedure inducing potentially severe complications. Postoperative peritonitis after abdominal surgery occurs mostly when the digestive lumen and the peritoneum communicate but in rare situation, no underlying digestive fistula can be found. The aim of this study was to report this situation after CCRS plus HIPEC, which has not been described yet and for which the treatment is not yet well defined. Between 1994 and 2012, 607 patients underwent CCRS plus HIPEC in our tertiary care center and were retrospectively analyzed. Among 52 patients [9%] reoperated for postoperative peritonitis, no digestive fistula was found in seven [1%]. All had a malignant peritoneal pseudomyxoma with an extensive disease [median Peritoneal Cancer Index: 27]. The median interval between surgery and reoperation was 8 days [range: 3-25]. Postoperative mortality was 14%. Five different bacteriological species were identified in intraoperative samples, most frequently Escherichia coli [71%]. The infection was monobacterial in 71%, with multidrug resistant germs in 78%. Postoperative peritonitis without underlying fistula after CCRS plus HIPEC is a rare entity probably related to bacterial translocation, which occurs in patients with extensive peritoneal disease requiring aggressive surgeries. The principles of treatment do not differ from that of other types of postoperative peritonitis.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma

<p><b>INTRODUCTION</b>Peritoneal mesothelioma is a rare neoplasm. Due to the limited understanding of its biology and behaviour, peritoneal mesothelioma poses a diagnostic and management challenge. The management of peritoneal mesothelioma has been controversial; systemic chemotherapy, palliative surgery and cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) have been described.</p><p><b>MATERIALS AND METHODS</b>This study shares our experience with cytoreductive surgery and HIPEC for 5 out of the 6 cases of peritoneal mesotheliomas treated surgically, at a single institution in Singapore over the past 2 years. Computed tomography (CT) scans, positron emission tomography (PET)-CT scans and tumour markers were performed preoperatively but were not conclusive for the disease. All 6 cases presented to the Department of Surgical Oncology at National Cancer Centre Singapore, were diagnosed by histology of intraoperative biopsies. The combination of aggressive cytoreductive surgery and HIPEC was performed in 5 patients, with abandonment of procedure in 1 with extensive disease, who was treated with systemic chemotherapy instead.</p><p><b>RESULTS</b>Median duration of surgery, median length of hospital stay, and median follow-up duration were 7.04 hours, 11 days, and 15 months respectively. One postoperative morbidity relating to chemical peritonitis required exploratory laparotomy with good outcome. There were no mortality. All patients are alive at the last follow-up with no evidence of recurrences at 4 to 31 months from the time of their surgery.</p><p><b>CONCLUSION</b>Peritoneal mesothelioma is a rare disease that requires early diagnosis and can be effectively treated by CRS and HIPEC in selected group of patients.</p>

Isolated limb perfusion with hyperthermia and chemotherapy: predictive factors for regional toxicity

OBJECTIVE: Isolated limb perfusion combined with melphalan is an accepted treatment for obtaining locoregional control in advanced melanoma of the extremities and other malignant neoplasias restricted to the limb. This study aims to examine the factors associated with toxicity caused by the regional method. We considered the technical aspects of severe complications associated with the procedure in an attempt to diminish the patient morbidity that occurs during the learning curve. METHODS: We conducted a retrospective analysis of the records of patients who underwent perfusion at the AC Camargo Hospital in São Paulo, Brazil between January 2000 and January 2009. The Wieberdink scale was applied to classify local toxicity and its relation to clinical and laboratory variables. RESULTS: Fifty-eight perfusions were performed in 55 patients. Most patients (86.2%) presented a toxicity level between I and III. Grade V toxicity was seen in five cases (8.6%), four of which occurred in the first 2 years. Creatine phosphokinase, an important predictive factor for toxicity, had an average value of 231.8 for toxicity grades I-III and 1286.2 for toxicity grades IV-V (p = 0.001). There was a relationship between the melphalan dose and toxicity, which was 77 mg (25 to 130 mg) for toxicity grades I-II and 93.5 mg (45 to 120 mg) for toxicity grades IV-V (p = 0.0204). CONCLUSION: It is possible to prevent the toxicity associated with melphalan by adjusting the dose according to the patient's body weight (especially for women and obese patients) and the creatine phosphokinase values in the postoperative period.

Isolated limb hyperthermic perfusion chemotherapy for melanoma of the extremities / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of isolated limb hyperthermic perfusion chemotherapy for melanoma of the extremities.</p><p><b>METHODS</b>Limb isolated hyperthermic perfusion chemotherapy was performed in 41 patients with malignant melanoma of the extremities, and then the primary lesions in 24 patients were removed at 14 - 21 days after chemotherapy. Tumor necrosis was examined by pathology.</p><p><b>RESULTS</b>Among the 41 patients, 40 cases were followed up for 6-113 months, and one was lost. There was no local recurrence in those patients. 29 cases were followed up for more than 3 years, and 26 of them were surviving. Forteen cases were followed up for more than five years, among them 9 cases were surviving. The 3-year and 5-year survival rates of the whole group were 95.0% and 70.0%, respectively. The average reduction of the tumor volume was 55.6% after perfusion. The pathological examination showed that tumor necrosis was 90% - 100% (complete response) in 21 cases (87.5%) and 60% - 89% (partial response) in 3 cases (12.5%).</p><p><b>CONCLUSIONS</b>The isolated limb hyperthermic perfusion chemotherapy is an effective treatment of limb malignant melanoma. It can significantly reduce the local recurrence rate, and improve the 5-year survival rate, prognosis and the quality of life of the patients.</p>

Effect of intraoperative intraperitoneal chemotherapy and postoperative nutritional support on intestinal permeability and cellular immune function in patients with advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of hyperthermic intraoperative intraperitoneal chemotherapy(HIIC) and postoperative nutritional support on the intestinal permeability and the cellular immunity function in patients with advanced gastric cancer.</p><p><b>METHODS</b>All the patients diagnosed as advanced gastric cancer in the Gastric Tumor Diagnosis and Treatment Center of Jiangsu Cancer Hospital were randomly divided into three groups using random digit table:(1)EN group treated with enteral nutrition during postoperative period; (2)HIIC+EN group treated with HIIC combined with postoperative enteral nutrition;(3)HIIC+PN group treated with HIIC combined with postoperative parenteral nutrition. Index of lactulose/mannitol(L/M) ratio was used to evaluate the permeability of intestinal mucosa. The percentage of CD4(+), CD8(+) and NK cell, the ratio of CD4/CD8 T cell in peripheral blood were tested by flow cytometry. The time points of these measurements were the day before surgery, postoperative days (POD) 3, 7, and 12.</p><p><b>RESULTS</b>Compared with the day before surgery(POD-1), the ratio of L/M on POD+3 increased significantly in all the three groups(0.1235±0.0611 vs. 0.0280±0.0183, 0.1648±0.0571 vs. 0.0305±0.0208, 0.1702±0.0628 vs. 0.0298±0.0229)(P<0.05) and then decreased gradually. The L/M ratio of EN(0.0278±0.0217) and HIIC+EN(0.0336±0.0235) groups recovered to the baseline on POD+12, however HIIC+PN group still had elevated L/M ratio(0.0616±0.0430). The percentage of CD4(+)T cell and the ratio of CD4/CD8 in HIIC+EN group and HIIC+PN group were significantly lower than those in EN group(P=0.033, P=0.002, respectively). Compared with the POD-1,the percentage of CD4(+)T cell and the ratio of CD4/CD8 in HIIC+EN group and EN group on POD+12 were increased significantly(P<0.05).</p><p><b>CONCLUSIONS</b>HIIC may cause significant increase in intestinal permeability and inhibit cellular immunity in patients undergoing radical resection for advanced gastric cancer. Mucosal permeability can be reversed by enteral nutrition.</p>

Literature review of the efficacy and safety of hyperthermic intraperitoneal perfusion chemotherapy after cytoreductive surgery in the treatment of pseudomyxoma peritonei / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluated the safety and efficacy of hyperthermic intraperitoneal perfusion chemotherapy(HIPC) in the prevention and treatment of pseudomyxoma peritonei (PMP) recurrence after cytoreductive surgery(CRS).</p><p><b>METHODS</b>Studies published in English before 2010 on HIPC after CRS for PMP were searched in PubMed database. Each study was carefully evaluated based on pre-determined criteria. Study results were comprehensively displayed in a form. A descriptive systematic review was performed.</p><p><b>RESULTS</b>A total of 11 studies were included. The median survival time of patients in these studies ranged from 25.6 months to 156 months. The ranges of 1-year, 2-year, 3-year, 5-year, and 10-year survival rates were 72%-100%, 55%-96%, 59%-96%, 52%-96%, and 55%-96%, respectively. The overall complication rate ranged from 2%-15%, and the total perioperative mortality were from 0 to 7%.</p><p><b>CONCLUSION</b>HIPC after CRS is effective and safe for patients with PMP.</p>