[Contribution of intraperitoneal chemotherapy in the treatment of colorectal peritoneal carcinoma. HIPEC, PIPAC, state of the art and future directions]. / La chimiothérapie intra-péritonéale dans le traitement de la carcinose péritonéale d'origine colorectale. CHIP, PIPAC, état des lieux et perspectives.

After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.

The impact of the extent of surgery on late adverse effects following cytoreductive surgery and HIPEC.

AIM: To investigate the impact of the surgical extent on late adverse effects (LAE) following cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). METHOD: A prospective cohort study including patients undergoing CRS + HIPEC due to peritoneal metastases from gastrointestinal tumour origin. From 2006 through 2019, consecutive patients treated with CRS + HIPEC were followed at 3, 6 and 12 months, and LAEs were assessed using the symptom scales and items from the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30). Surgical extent was categorized into three groups (major, intermediate, minor) based on peritonectomy procedures and colorectal resections performed as part of CRS. EORTC data were analysed using a linear mixed effects regression model adjusted for age, gender, origin of tumour and comorbidity. RESULTS: In total, 257 patients who responded to at least one questionnaire during the follow-ups were included. Only diarrhoea symptoms were positively associated with surgical extent (mean differences: major vs. minor: 8.4 (-0.5; 17.2) (p = 0.06) and major vs. intermediate: 10.9 (3.8; 18.0) (p = 0.00)). Additionally, diarrhoea symptoms persisted throughout the study period and did not change over time (mean difference 12-3 months: -3.6 (-9.1; 1.7) (p-value = 0.18)). Overall, the levels of different symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, and appetite loss) significantly decreased from 3 to 12 months. CONCLUSION: Patients undergoing extensive CRS suffer from persistent impaired gastrointestinal function in terms of diarrhoea compared patients undergoing to less extensive surgery. Attention should be directed at detecting such LAE and to guide patients accordingly.

Application of HIPEC simulations for optimizing treatment delivery strategies.

INTRODUCTION: Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) aims to treat microscopic disease left after CytoReductive Surgery (CRS). Thermal enhancement depends on the temperatures achieved. Since the location of microscopic disease is unknown, a homogeneous treatment is required to completely eradicate the disease while limiting side effects. To ensure homogeneous delivery, treatment planning software has been developed. This study compares simulation results with clinical data and evaluates the impact of nine treatment strategies on thermal and drug distributions. METHODS: For comparison with clinical data, three treatment strategies were simulated with different flow rates (1600-1800mL/min) and inflow temperatures (41.6-43.6 °C). Six additional treatment strategies were simulated, varying the number of inflow catheters, flow direction, and using step-up and step-down heating strategies. Thermal homogeneity and the risk of thermal injury were evaluated. RESULTS: Simulated temperature distributions, core body temperatures, and systemic chemotherapeutic concentrations compared well with literature values. Treatment strategy was found to have a strong influence on the distributions. Additional inflow catheters could improve thermal distributions, provided flow rates are kept sufficiently high (>500 mL/min) for each catheter. High flow rates (1800 mL/min) combined with high inflow temperatures (43.6 °C) could lead to thermal damage, with CEM4310 values of up to 27 min. Step-up and step-down heating strategies allow for high temperatures with reduced risk of thermal damage. CONCLUSION: The planning software provides valuable insight into the effects of different treatment strategies on peritoneal distributions. These strategies are designed to provide homogeneous treatment delivery while limiting thermal injury to normal tissue, thereby optimizing the effectiveness of HIPEC.

[Preoperative Prognostic Factors in CRS plus HIPEC for Patients with Peritoneal Dissemination of Colorectal Cancer].

Peritoneal dissemination of colorectal cancer has the poorest prognosis among metastatic sites, with an average overall survival of less than 6 months. Various treatment methods have been reported for these patients, and recently there have been several reports showing the usefulness of cytoreductive surgery(CRS)combined with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the studies on this treatment are limited. In this study, we retrospectively reviewed cases of CRS plus HIPEC. Twenty-one patients who underwent CRS plus HIPEC at Tokyo Medical University Hospital and Toda Central General Hospital between August 2014 and December 2017 were included in this study. The long-term and short-term survival groups were analyzed separately, and predictors of preoperative treatment efficacy were examined. The surgical approach was open in 16 cases and laparoscopic in 5 cases. Complete resection was achieved in 10 of these patients. Postoperative complications occurred in 6 patients. There were no deaths within 90 days of surgery. The median overall survival was 17.0 months, and the 1-year survival rate was 65%. Median progression-free survival was 11.0 months. In a multivariate analysis predicting long-term versus short-term survival groups, sex, primary tumor location, and P factor were independent predictors of treatment response. CRS plus HIPEC therapy is considered an effective treatment option. The predictors of preoperative treatment response include sex, primary tumor location, and P factor.

Depression, Anxiety, Stress and Distress Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Results of a Prospective Cohort Study.

The aim of this study was to describe the levels of depression, anxiety, stress, and distress in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The 21-item Depression, Anxiety and Stress Scale (DASS-21) and Distress Thermometer were administered preoperatively, postoperatively day 10, and at hospital discharge to 169 patients with peritoneal carcinomatosis undergoing CRS and HIPEC. The mean preoperative values for DASS-21 subscale scores were 4.7 (depression), 4.2 (anxiety), and 8.4 (stress), and the mean preoperative Distress Thermometer rating was 4.0. No significant changes in levels of depression, stress, or distress were noted thereafter. The DASS-21 anxiety subscale score significantly increased at hospital discharge (p = .005). Higher levels of preoperative psychological depression, anxiety, stress and distress were associated with worse mental component scores. Higher preoperative depression levels were associated with the provision of more clinical psychologist occasions of service, and higher preoperative distress levels were associated with younger age. Preoperative psychological measures are important for ensuring CRS and HIPEC patients that require additional support are identified and provided with ongoing psychological interventions.

Feasibility of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced peritoneal surface tumors during the COVID-19 pandemic: A single-institution experience.

BACKGROUND AND OBJECTIVES: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex treatment used in selected patients with peritoneal surface malignancies. HIPEC procedures are time and resource intensive. The primary aim of this analysis was to compare the experience of treating advanced abdominal tumors with CRS-HIPEC before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Patients included in this analysis received CRS-HIPEC at a single center during either a prepandemic (March 18, 2019-March 17, 2020) or pandemic (March 18, 2020-February 5, 2021) interval. A retrospective chart review was performed. RESULTS: Our analysis included 67 patients: 30 (45%) treated prepandemic and 37 (55%) treated during the pandemic. Median age at the time of operation was 58 years (interquartile range: [49-65]); 53% of patients were women. Patients treated during the pandemic presented with higher peritoneal cancer index (PCI) scores with 32% (n = 12) having a PCI > 20 at the time of surgery (p = 0.01). Five patients had delays in surgery due to the pandemic. Rates of overall postoperative morbidity, reoperation, and readmission were not different between the cohorts. CONCLUSIONS: Despite presenting with more extensive disease, patients treated with CRS-HIPEC during the height of the COVID-19 pandemic had comparable perioperative outcomes to patients treated prepandemic.

Effect of hyperthermic intraperitoneal chemotherapy in combination with cytoreductive surgery on the prognosis of patients with colorectal cancer peritoneal metastasis: a systematic review and meta-analysis.

BACKGROUND: Peritoneal metastasis often occurs in patients with colorectal cancer peritoneal metastasis, and the prognosis is poor. A large body of evidence highlights the beneficial effects of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is little consensus on the optimal treatment strategy for patients with colorectal cancer peritoneal metastasis. The purpose of this study is to evaluate the impact of CRS + HIPEC on survival and provide reference for the treatment of patients with colorectal cancer peritoneal metastasis. METHODS: This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov databases were screened from inception of the review to March 11, 2022. Ten studies were included in qualitative and quantitative analysis. RESULTS: A total of 3200 patients were enrolled in the study, including 788 patients in the CRS and HIPEC groups and 2412 patients in the control group, of which 3 were randomized controlled trials and 7 were cohort studies. The 3 randomized controlled studies were of high quality, and the quality scores of the 7 cohort studies were all 7 or above, indicating high quality. The results showed that the OS of CRS + HIPEC group was higher than that of control group (HR: 0.53, 95% CI: 0.38-0.73; P < 0.00001, I2 = 82.9%); the heterogeneity of the studies was large. The subgroup analysis showed that the OS of CRS and HIPEC group was higher than that of PC group (HR: 0.37, 95% CI: 0.30-0.47; P = 0.215, I2 = 31%) and higher than that in CRS group (HR: 0.73, 95% CI: 0.49-1.07; P = 0.163, I2 = 44.8%); the heterogeneity of the studies was low. In the OPEN group, the OS of THE CRS and HIPEC groups was higher than that in the control group (HR: 0.51, 95% CI: 0.38-0.70; P = 0.353, I2 = 3.9%); OPEN group showed lower heterogeneity. The OS of 60-100-min group was higher than that in the control group (HR: 0.65, 95% CI: 0.49-0.88; P = 0.172, I2 = 37.4%); the heterogeneity of the studies was low. Sensitivity analysis showed that there was no significant difference in the results of the combined analysis after each study was deleted. The results of publication bias showed that the P-value of Egger and Begg tests was 0.078 > 0.05, indicating that there is no publication bias. CONCLUSIONS: CRS + HIPEC can improve the survival rate of patients with colorectal cancer peritoneal metastasis.

Palliative Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis: Is It Safe and Effective?

INTRODUCTION: Palliation is a controversial indication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients with peritoneal carcinomatosis (PC) are living longer, and the roles of palliative CRS and HIPEC are increasingly challenged. The purpose of this study is to evaluate indications, morbidity, and symptom improvement from CRS/HIPEC in advanced PC. METHODS: A retrospective review of patients undergoing CRS and/or HIPEC with a palliative intent at a single institution from February 2008 to February 2018 was performed. Main end points included symptom improvement, symptom-free interval, and overall survival. RESULTS: Two hundred and seventy seven patients were referred for CRS/HIPEC during the study period and 17 underwent 20 palliative procedures. Appendiceal (n = 6) and colorectal cancers (n = 6) were the most common malignancies. Ascites (n = 8) and bowel obstruction (n = 8) were the most common indications for intervention. The postoperative complication rate was 50% and major complication rate was 20%. Partial symptom improvement or resolution of symptoms was achieved in 18 (90%) cases. A durable symptom control at 90 d was achieved in 13 (65%) cases. The median time to symptom recurrence was 5.1 mo (interquartile range: 2-11.4), and the median overall survival was 11.6 mo (interquartile range: 3.8-28.5). CONCLUSIONS: Palliative CRS and/or HIPEC achieve symptom improvement in patients with advanced PC. Risk assessment and expected time to recovery from surgery remain paramount for patient selection.

Diagnostic Laparoscopy in Patients With Peritoneal Carcinomatosis Is Safe and Does Not Delay Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) among patients with peritoneal carcinomatosis (PC) depend largely on the extent of peritoneal disease. Since PC is not reliably evaluated with cross-sectional imaging, tumor burden is often evaluated with diagnostic laparoscopy (DLS). The aims of this study are to evaluate the safety of DLS in patients with peritoneal disease and determine if DLS delays time to CRS-HIPEC. METHODS: We performed an institutional retrospective review of 145 patients who underwent CRS-HIPEC between 2013 and 2020. Patients were divided into 2 groups: those who underwent an electively scheduled DLS prior to CRS-HIPEC and those who did not. Intraoperative and postoperative complications associated with DLS were determined from the surgeon's operative report. Time from diagnosis of PC to CRS-HIPEC was compared between the 2 groups. RESULTS: Of the 145 patients available for analysis, 47% (68) underwent DLS and 44% (64) did not. Of all the diagnostic laparoscopies performed, there was 1 (1.5%) intraoperative complication. The duration between diagnosis of peritoneal carcinomatosis and surgery was 4.9 months among patients who underwent DLS prior to CRS-HIPEC and 4.3 months among patients who did not (P = .79). CONCLUSION: In this retrospective analysis, diagnostic laparoscopy prior to CRS-HIPEC demonstrated a comparable rate of DLS-associated complications compared to other gastrointestinal malignancies and does not prolong time from diagnosis to CRS-HIPEC. Thus, in patients undergoing evaluation for CRS-HIPEC, diagnostic laparoscopy provides significant value in patient selection without incurring perioperative risk or delay in CRS-HIPEC.

Advances with pharmacotherapy for peritoneal metastasis.

INTRODUCTION: A new treatment strategy involving cytoreductive surgery (CRS) combined with perioperative intraperitoneal (IP) chemotherapy was proposed in 1999 by the Peritoneal Surface Oncology Group International, and the strategy is now justified as a state-of-the-art treatment to improve the long-term survival of patients with peritoneal metastasis (PM). To achieve cure in the patients with PM, complete removal of macroscopic tumors and eradication of micrometastasis on the peritoneum, left after CRS are essential. Systemic chemotherapy is not indicated for the treatment of PM. In contrast, intraperitoneal (IP) chemotherapy brings about significantly higher locoregional dose intensity in the peritoneal cavity and subperitoneal tissues. In combination with anticancer drugs, hyperthermia enhances cytotoxicity against cancer cells. AREA COVERED: This article provides a systematic overview of PM from various cancers including gastric, colorectal, small bowel, appendiceal cancer, and mesothelioma. It also includes all the essential aspects of therapy. EXPERT OPINION: CRS plus perioperative intraperitoneal chemotherapy is safe with acceptable morbidity and mortality. It is justified as a standard treatment to improve the long-term survival of patients with PM and is now performed with curative intent for PM from various malignancies.

Isolated limb perfusion for soft tissue sarcoma: Current practices and future directions. A survey of experts and a review of literature.

Soft tissue sarcomas constitute 1% of adult malignant tumors. They are a heterogeneous group of more than 50 different histologic types. Isolated limb perfusion is an established treatment strategy for locally advanced sarcomas. Since its adoption for sarcomas in 1992, after the addition of TNFα, few modifications have been done and although indications for the procedure are essentially the same across centers, technical details vary widely. The procedures mainly involves a 60 min perfusion with melphalan and TNFα under mild hyperthermia, achieving a limb preservation rate of 72-96%; with an overall response rates from 72 to 82.5% and an acceptable toxicity according to the Wieberdink scale. The local failure rate is 27% after a median follow up of 14-31 months compared to 40% of distant recurrences after a follow up of 12-22 months. Currently there is no consensus regarding the benefit of ILP per histotype, and the value of addition of radiotherapy or systemic treatment. Further developments towards individualized treatments will provide a better understanding of the population that can derive maximum benefit of ILP with the least morbidity.

Impact of Perfusate Concentration on Hyperthermic Intraperitoneal Chemotherapy Efficacy and Toxicity in a Rodent Model.

BACKGROUND: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be beneficial in treating limited peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Perfusate volume directly affects treatment concentration and therefore is a key parameter defining HIPEC; yet little is known about the impact of perfusate concentration on systemic toxicity and treatment morbidity. MATERIALS AND METHODS: PC was induced through intraperitoneal injection of human CRC cell lines. A novel perfusion model was developed to treat athymic nude mice with continuous circulation of adequately miniaturized volumes of heated perfusate. Oxaliplatin HIPEC was performed applying different volumes of perfusate with fixed doses or fixed concentrations. Early postoperative mortality and morbidity were assessed as well as long-term survival. In addition, antiproliferative and proapoptotic effects of HIPEC were determined in vitro and in vivo. RESULTS: Perfusate concentration crucially affected the toxicity of fixed-dose oxaliplatin HIPEC as indicated by postoperative weight loss and early postoperative mortality. Applying different perfusate volumes at a fixed concentration did not influence toxicity. Adequately miniaturized HIPEC with oxaliplatin did not exert relevant cytotoxic effects toward PC arising from human CRC cells in vivo. CONCLUSIONS: We describe a novel murine model that adequately miniaturizes all physical parameters of HIPEC as applied in humans. HIPEC drug concentration is a crucial parameter determining excess toxicity and should be better standardized. HIPEC with oxaliplatin fails to induce relevant antitumor activity or to improve survival in this murine model of PC from CRC.

Oncologic outcomes and morbidity following heated intraperitoneal chemotherapy at cytoreductive surgery for primary epithelial ovarian cancer: A systematic review and meta-analysis.

OBJECTIVES: Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death. RESULTS: We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46-77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20-52) and 0% (95% CI 0-5) respectively. CONCLUSION: One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC.

Relapse and Prognosis of Non-Muscle Invasive Bladder Cancer After Combined HOLRBT with Sunitinib and TGC Perfusion Chemotherapy.

Objective: To prevent postoperative relapse after HOLRBT, we compared postoperative adjuvant therapies. Methods: One hundred fifty patients with non-muscle invasive bladder cancer (NMIBC) were meanly divided into three groups: A, B, and C. Group A patients only took sunitinib, group B patients underwent TGC perfusion chemotherapy, and group C patients took sunitinib and underwent TGC chemotherapy. Results: It was discovered that TGC perfusion chemotherapy combined with taking sunitinib can significantly reduce the relapse rate. Most of the tumor relapse period was assembled at 9 months after the operation. No-tumor relapse survival rate and no-fluorescence in situ hybridization positive survival rate in Group C were significantly higher than those of Group A and Group B. Conclusion: Therefore, the combined application of taking sunitinib drug and going through TGC perfusion chemotherapy after secondary HOLRBT will evidently improve the prognosis of patients with a glorious applicated prospect.

Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results.

BACKGROUND: The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. METHODS: Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2 ). RESULTS: Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2 ) and four at dose level 3 (75 mg/m2 ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3). CONCLUSION: Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.

ANTECEDENTES: El papel de la cirugía citorreductora (cytoreductive surgery, CRS) combinado con la quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) en el cáncer gástrico no está definido. Este estudio fase I-II no aleatorizado de escalado de dosis fue diseñado para evaluar la seguridad y la viabilidad de HIPEC, después de la quimioterapia sistémica, en pacientes con cáncer gástrico con diseminación peritoneal limitada. Además, se exploró la máxima dosis tolerada (maximum tolerated dose, MTD) de docetaxel intraperitoneal normotérmico en combinación con una dosis fija de oxaliplatino intraperitoneal. MÉTODOS: Se incluyeron pacientes con adenocarcinoma gástrico cT3-cT4a resecable con metástasis peritoneales limitadas y/o citología peritoneal positiva. Se utilizó una técnica HIPEC abierta con 460 mg/m2 de oxaliplatino hipertérmico (30 minutos) seguido de docetaxel normotérmico (90 minutos) en dosis crecientes (0, 50, 75 mg/m2 ). RESULTADOS: Entre 2014 y 2017, se incluyeron 37 pacientes. De los 25 pacientes que completaron la totalidad del protocolo del estudio, 4 pacientes fueron tratados en el nivel de dosis 1 (0 mg/m2 de docetaxel), 6 pacientes en el nivel de dosis 2 (50 mg/m2 ) y 4 pacientes en el nivel de dosis 3 (75 mg/m2 ). En el nivel de dosis 3, se produjeron dos casos de toxicidad limitante de dosis (dose-limiting toxicities, DLTs), ambas asociadas con un íleo postoperatorio. Posteriormente, otros 11 pacientes fueron tratados con el nivel de dosis 2, y no se produjeron más DLTs. La MTD de docetaxel intraperitoneal fue de 50 mg/m2 . Se registraron efectos adversos graves en 17 de 25 pacientes. La tasa de reoperación fue del 16% (n = 4) y la mortalidad relacionada con el tratamiento fue del 8% (n = 2; ambos en el nivel de dosis 3).

Non-medical caregivers and the use of intraperitoneal chemotherapy in the operating theatre: A survey on the perception of safety.

BACKGROUND: In the last two decades, intraperitoneal(IP) chemotherapy during surgery achieved recognition in the management of peritoneal metastases. Occupational hazard became a concern leading to standardized safety measures. The aim of this study is to evaluate the perceived level of information and protection among the non-medical caregivers involved in HIPEC and PIPAC in a high-volume center. METHODS: All non-medical caregivers in the operating theatre of our institution were asked to answer a questionnaire between April and May 2018. The questionnaire included multiple choice questions and open questions structured in four parts: demographic variables, perceived level of information, perceived level of protection, interest in further education. RESULTS: Forty-nine caregivers agreed to answer the questionnaire. All identified IP chemotherapy as an occupational risk. Thirty-eight persons (77.55%) trusted the protective value of safety measures during HIPEC compared to 32 (65.3%) during PIPAC. A total of 29 persons (59.18%) used some of the measures while 16 (32.65%) used all of them. Main reasons of non-use were slips and lapses (7 persons) and lack of comfort (4 persons). A total of 34 caregivers considered the level of information about safety protocols as good or very good (69%). A total of 46 persons considered the level of protection as satisfying or excellent (93.87%). A total of 36 (73.47%) interviewees expressed the need of receiving more information. CONCLUSIONS: The present study shows that non-medical caregivers in the operating theatres are aware of the occupational hazards related to the use of IP chemotherapy. The use of protective measures is associated with decreased level of perceived risk. However there is a high need of continuous education on this subject for the involved personnel.

The importance of synchronicity in the management of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Colorectal peritoneal metastases (CPM) occur in up to 13% of patients with colorectal cancer, presenting either synchronously or metachronously. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) have been increasingly utilised for selected CPM patients with favourable outcomes, though its benefits may differ for synchronous (s-CPM) and metachronous CPM (m-CPM). METHODS: A retrospective analysis of CPM patients treated with CRS and HIPEC at the National Cancer Centre Singapore over 15 years was performed. In the s-CPM group, CPM was diagnosed at primary presentation with CRS and HIPEC performed at the time of or within 6 months from primary surgery. In the m-CPM group, patients developed CPM > 6 months after primary curative surgery. RESULTS: One hundred two patients with CPM were treated with CRS and HIPEC. Twenty (19.6%) patients had s-CPM and 82 (80.4%) had m-CPM. Recurrences occurred in 45% of s-CPM and in 54% of m-CPM (p = 0.619). Median overall survival was significantly prolonged in patients with m-CPM (45.2 versus 26.9 months, p = 0.025). In a subset of m-CPM patients with limited PCI in whom ICU stay was not required, a survival advantage was seen (p = 0.031). CONCLUSION: A survival advantage was seen a subset of m-CPM patients, possibly representing differences in disease biology.

Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review.

The purpose of the present review was to describe evidence-based indications for hyperthermic intraperitoneal chemotherapy (HIPEC), with cytoreductive surgery (CRS), in patients with a diagnosis of mesothelioma, appendiceal (including appendiceal mucinous neoplasm), colorectal, gastric, ovarian or primary peritoneal carcinoma. Relevant studies were identified from a systematic MEDLINE and EMBASE search of studies published from 1985 to 2019. Studies were included if they were RCTs. If no RCTs were identified, prospective and retrospecctive comparative studies (where confounders are controlled for studies with greater than 30 patients) were included. Overall survival, progression-free survival, recurrence-free survival, adverse events and quality of life data were extracted. For patients with newly diagnosed, primary stage III epithelial ovarian, fallopian tube or primary peritoneal carcinoma, HIPEC with CRS should be considered for those with at least stable disease following neoadjuvant chemotherapy at the time of interval CRS if complete or optimal cytoreduction is achieved. There is insufficient evidence to recommend the addition of HIPEC when primary CRS is performed for patients with newly diagnosed, primary advanced epithelial ovarian, fallopian tube or primary peritoneal carcinoma or in those with recurrent ovarian cancer outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of peritoneal colorectal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS for the prevention of or for the treatment of gastric peritoneal carcinomatosis outside of a clinical trial. There is insufficient evidence to recommend HIPEC with CRS in patients with malignant peritoneal mesothelioma or in those with disseminated mucinous neoplasm in the appendix as a standard of care; however, these patients should be referred to HIPEC specialty centres for assessment for treatment as part of an ongoing research protocol.

Diaphragmatic Peritoneal Stripping Versus Full-Thickness Resection in CRS/HIPEC: Is There a Difference?

BACKGROUND: Pleural recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rare and poorly delineated. Specifically, data are limited on the effect that diaphragmatic peritoneal stripping versus full-thickness resection has on the nature of ipsilateral pleural recurrence and postoperative morbidity. METHODS: Patients with peritoneal carcinomatosis who underwent CRS/HIPEC were included from a prospectively maintained database. The patients were divided into three cohorts based on surgical management of the diaphragm as follows: diaphragm-stripping (DS) cohort, full-thickness resection (FTR) cohort, and no diaphragm manipulation (ND) cohort. Postoperative morbidity and incidence of ipsilateral pleural recurrence were evaluated. All diaphragmatic defects were closed before abdominal chemoperfusion. RESULTS: The inclusion criteria were met by 409 CRS/HIPEC procedures: 66 in DS, 122 in FTR, and 238 in ND. Ipsilateral pleural recurrence rates did not differ significantly between the three cohorts (DS 6%, FTR 3%, ND 3%; p = 0.470). Postoperative respiratory complications and overall morbidity were significantly greater for the patients who underwent diaphragmatic disruption (stripping and/or resection) than for the patients who did not (p ≤ 0.0001), but the two groups did not differ in terms of 30-day mortality. However, comparison of FTR with DS showed no impact on major morbidity or pleural recurrence. CONCLUSION: Although patients undergoing surgical manipulation of the diaphragm during CRS/HIPEC experienced significantly greater morbidity, diaphragmatic stripping did not differ from full-thickness resection in terms of grades 3 and 4 complications or incidence of ipsilateral pleural recurrences. When deemed necessary to achieve complete cytoreduction, full-thickness diaphragmatic resection should be undertaken. In addition, the data support the observation that definitive repair of the diaphragmatic defect before abdominal chemoperfusion does not adversely influence ipsilateral pleural recurrence.