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Background: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC., Methods: A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0., Results: One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC., Conclusions: PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication., Competing Interests: Declaration of competing interest The authors report no conflicts of interest relevant to this article., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: PIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment., Methods: All patients diagnosed with unresectable PM who became resectable throughout PIPAC treatment were included. Outcome criteria were adverse events following PIPAC procedure and rate of secondary CRS and HIPEC., Results: Four hundred thirty-seven PIPAC were done in 146 consecutive patients. Among them, 26 patients (17.8%) who underwent 76 PIPAC were scheduled for CRS and HIPEC after reduction of the peritoneal burden. PM were from gastric, peritoneal mesothelioma, ovarian, colorectal and small bowel in 13, 7, 4, 1 and 1 patients, respectively. At the time of the first PIPAC, median age was 58.6 years (32-76.3). Median PCI was 16 (1-39). All patients had systemic chemotherapy in between PIPAC session. Median consecutive PIPAC procedure was 3 (1-8). Complications occurred in 3 PIPAC session (4%) and there was no major complication (CTCAE III or higher). Complete CRS and HIPEC was achieved in 21 patients of the 26 scheduled (14.4%). The remaining 5 patients were considered unresectable at the exploratory laparotomy. Among patients who underwent CRS and HIPEC, with median follow-up of 7 (1-26) months, 14 patients (66.7%) were alive without recurrence, 2 patients (9.5%) were alive with recurrence and 5 patients (23.8%) died., Conclusions: Complete CRS and HIPEC can be achieved in strictly selected patient with unresectable PM at diagnosis after repeated PIPAC session with palliative intent., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising technic for unresectable peritoneal metastasis (PM). Targeted therapies such as bevacizumab have demonstrated their efficacy in advanced colorectal and ovarian cancer. We aimed to evaluate the feasibility and safety of this bidimensional therapeutic association., Methods: A prospectively maintained PIPAC database was retrospectively analyzed from December 2015 to March 2018. All patients who underwent PIPAC for unresectable PM were selected. Patients with systemic chemotherapy including bevacizumab (BEVA group) were compared with patients with systemic chemotherapy without bevacizumab (NON-BEVA group). Major morbidity and mortality were analyzed., Results: 134 patients underwent 397 PIPAC in Lyon Sud University Hospital. 26 Patients had 88 PIPAC in the BEVA group were compared to 108 patients who had 309 PIPAC in the NON-BEVA group. Patients in the BEVA group demonstrated a higher Peritoneal Cancer Index (PCI 20 vs. 16, p < 0.001). There was no statistical difference in overall 30-day morbidity (BEVA: 13 (14.8%) vs NON-BEVA: 29 (9.4%); p = 0.147). There was no statistical difference for grade III-IV complications (BEVA: 4 (4.5%) vs NON-BEVA 10 (3.2%); P = 0.521). Major complications from BEVA group were as follow, 2 bowel obstructions, one hematoma and one severe hypersensitivity reaction to platinum compound. There was no 30-day mortality in the BEVA group compared to 6 (5.5%) mortality in the NON-BEVA group., Conclusion: PIPAC associated with bevacizumab is feasible, safe and well tolerated. The potential oncologic benefit of the concomitant use of bevacizumab and PIPAC remains to be evaluated., (Copyright © 2019. Published by Elsevier Ltd.)

Background: PIPAC is a new treatment modality for peritoneal cancer which has been practiced and evaluated until very recently by few academic centers in a highly standardized manner. Encouraging oncological outcomes and the safety profile have led to widespread adoption. The aim of this study was to assess current PIPAC practice in terms of technique, treatment and safety protocol, and indications., Methods: A standardized survey with 82 closed-ended questions was sent online to active PIPAC centers which were identified by help of PIPAC training centers and the regional distributors of the PIPAC-specific nebulizer. The survey inquired about center demographics (n = 8), technique (n = 34), treatment and safety protocol (n = 34), and indications (n = 6)., Results: Overall, 62 out of 66 contacted PIPAC centers answered the survey (response rate 93%). 27 centers had performed >60 PIPAC procedures. A consensus higher than 70% was reached for 37 items (50%), and higher than 80% for 28 items (37.8%). The topics with the highest degree of consensus were safety and installation issues (93.5% and 80.65%) while chemotherapy and response evaluation were the least consensual topics (63.7 and 59.6%). The attitudes were not influenced by volume, PIPAC starting year, type of activity, or presence of peritoneal metastases program., Conclusion: Homogeneous treatment standards of new techniques are important to guarantee safe implementation and practice but also to allow comparison between cohorts and multi-center analysis of merged data including registries. Efforts to avoid diversification of PIPAC practice include regular update of the PIPAC training curriculum, targeted research and a consensus statement., Competing Interests: Declaration of competing interest No conflicts of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: Epithelial ovarian cancer (EOC) is a poor prognosis disease partly linked to diagnosis at an advanced stage. The quality of care management is a factor that needs to be explored, more specifically optimal organisation of first-line treatment., Methods: A retrospective study, dealing with all patients diagnosed within the Rhone-Alpes region with initial diagnosis EOC in 2012, was performed. The aim was to describe the impact of multidisciplinary tumour boards (MTB) in the organisation of care and the consequence on the patient's outcomes., Results: 271 EOC were analysed. 206 patients had an advanced EOC. Median progression-free survival (PFS) is 17.8 months (CI95%, 14.6-21.2) for AOC. 157 patients (57.9%) had a front-line surgery versus 114 patients (42.1%) interval debulking surgery. PFS for AOC patients with no residual disease is 24.3 months compared with 15.3 months for patients with residual disease (p = .01). No macroscopic residual disease is more frequent in the patients discussed before surgery in MTB compared with patients not submitted before surgery (73% vs. 56.2%, p < .001)., Conclusion: These results highlight the heterogeneity of medical practices in terms of front-line surgery versus interval surgery, in the administration of neoadjuvant chemotherapy and in the setting of MTB discussion., (© 2020 John Wiley & Sons Ltd.)

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) shows encouraging results for patients with unresectable peritoneal metastasis. Several reports demonstrated the safety of the procedure combined with systemic chemotherapy, with a low rate of complication. The aim of this study is to report severe hypersensitivity reactions to platinum compounds (SHRPC) during PIPAC procedures., Methods: All patients who underwent PIPAC for non-resectable PC in Lyon Sud University hospital were included in a prospective institutional database. All patients who presented a SHRPC after PIPAC were included in our analysis., Results: One hundred and thirty-two patients underwent 383 PIPAC procedures between December 2015 and December 2017. oxaliplatin's and cisplatin-doxorubicin's protocols were used in 71 and 312 PIPAC, respectively. Four patients (3%) developed SHRPC; two patients (2.8%) after oxaliplatin and two patients (0.6%) after cisplatin-doxorubicin protocols. SHRPC occurred during the 6th PIPAC with cisplatin-doxorubicin protocol and during 2nd and 3rd PIPAC of the oxaliplatin protocol. Three events appeared within 15 min and one event occurred 50 min following nebulization. All the SHRPC have been managed successfully without any complication., Conclusions: This is the first report of SHRPC after PIPAC. The physician must constantly keep this rare but life-threatening complication in mind, especially after repeated PIPAC administration or previous platinum-based systemic chemotherapy.

Background/aim: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal metastasis (PM). The aim of this study was to report renal toxicity for patients who received at least 3 repeated PIPAC procedures., Patients and Methods: All patients who underwent at least 3 PIPAC cycles of cisplatin (7.5 mg/m 2 ) and doxorubicin (1.5 mg/m 2 ) for unresectable PM from December 2015 to September 2017, were analysed regarding postoperative renal toxicity., Results: Among 103 patients registered in a prospective single center database, 43 patients underwent at least 3 PIPAC cycles representing a total of 175 PIPAC. Median age was 59.8 years, 24 (55.8%) patients were female and median BMI was 22.2 kg/m 2 Most common origins of PM were gastric 22 (51.1%) and ovarian 11 (25.6%) cancer. Median peritoneal cancer index (PCI) was 17 (range=5-39). For 39 (90.1%) patients, systemic chemotherapy was performed in addition to PIPAC. Forty-three (100%), 17 (39.5%), 14 (32.5%), 8 (18.6%), 3 (7%), 2 (4.7%) and 2 (4.7%) patients underwent three, four, five, six, seven, eight and nine PIPAC procedures, respectively. Repeated PIPAC did not induce significant acute nor cumulative renal toxicity in any patients., Conclusion: Repeated PIPAC did not induce clinically relevant renal toxicity. This study confirms the previous published results in a larger group of patients., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method offered in selected patients suffering from non-resectable peritoneal carcinomatosis (PC). As reported experience is still limited, we conducted a survey among active PIPAC centers aiming to report their technical approach and clinical findings., Methods: An online survey was sent to active PIPAC centers worldwide. The questionnaire consisted of 34 closed questions and was conducted over a period of 3 months beginning in March 2017., Results: Nine out of 15 contacted centers completed the questionnaire totaling 832 PIPAC procedures in 349 patients. Most common indications for PIPAC were PC from gastric, ovarian and colorectal origin. The mean time between each PIPAC procedure was 6-8 weeks. Seven of nine (77.8%) centers evaluate the PCI at every PIPAC procedure. At least four tissue samples for histopathology analysis were retrieved in 5 (55.6%). All centers (100%) use the same chemotherapy protocol: oxaliplatin at a dosage of 92mg/m 2 for PC of colorectal origin and a combination of cisplatin and doxorubicin at a dosage of 7.5mg/m 2 and 1.5mg/m 2 , respectively, for other types of PC. Eight centers (88.9%) perform routine radiological evaluation before first PIPAC and after third PIPAC., Conclusion: These data confirm that PIPAC procedures are homogeneously performed in established centers. Standardization of the procedure will facilitate future international multicenter prospective clinical trials., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Peritoneal carcinomatosis (PC) is a common evolution of abdominal cancers and is associated with poor prognosis in the absence of aggressive multimodal therapy.1 Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a safe and innovative approach, which enhances the effect of chemotherapy 2 without reported renal/hepatic toxicity.3,4 It requires mastery of technical aspects to reduce postoperative morbidity, increase effectiveness, and prevent caregiver chemotherapy exposure. We, therefore, report herein the surgical protocol after 2 years of implementation in our university center specialized in PC management, accompanied by a short video, to share our experience., Methods: The procedure was performed under general anesthesia and capnoperitoneum (12 mmHg, 37 °C) using two balloon trocars placed in the midline, in accordance with the open laparoscopic technique. Explorative laparoscopy allowed Sugarbaker peritoneal cancer index to be determined. Parietal biopsies were taken, and ascites was removed for peritoneal cytology. The nebulizer was inserted and connected to a high-pressure injector. A pressurized aerosol containing chemotherapy agents was then administered; cisplatin (7.5 mg/m 2 in 150 ml 0.9%NaCl) immediately followed by doxorubicin (1.5 mg/m 2 in 50 ml 0.9%NaCl), or oxaliplatin alone (92 mg/m 2 in 150 ml 0.9%NaCl), based on PC origin and chemotherapy history. The aerosol was kept in a steady-state for 30 min then exhausted through a closed filter system, and trocars were retracted. Each step is illustrated in the video., Conclusion: This video protocol provides a better understanding of the PIPAC procedure and the safety measures essential for this method of chemotherapy administration. It should help all teams wishing to implement a PIPAC therapy program.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure., Methods: Between January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCI ± 11 and age ± 20 years) treated with CRS and HIPEC by laparotomy., Results: Eight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210 min (150-300) vs 240 (210-360), with a median hospital stay of 12 days (9-18) vs 19 (13-33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group., Conclusion: Laparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have demonstrated promising results in the treatment of peritoneal carcinomatosis (PC). The purpose of this study was to assess the impact of this combined procedure on quality of life (QoL)., Materials and Methods: A prospective single centre study of 216 consecutive patients treated with CRS and HIPEC was conducted using the Gastro-Intestinal Quality of Life Index questionnaire (GIQLI), completed preoperatively and at 1, 3, 6 and 12 months., Results: Questionnaire compliance was 81%, 90%, 89%, 89% and 74% at baseline, 1, 3, 6 and 12 months respectively. QoL was significantly decreased up to 6 months and returned to baseline at 12 months. In multivariate analysis, factors decreasing QoL were origin of PC at 3 months, presence of stoma at 6 months and length of surgery over 270 min and disease recurrence at 12 months., Conclusions: Despite morbidity associated with CRS and HIPEC, QoL returned to baseline at one year after surgery. This treatment strategy should be considered for the treatment of peritoneal carcinomatosis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed., Results: An optimal cytoreductive surgery was possible in 92.2 % of patients. Mortality and morbidity rates were 0.37 % and 11.6 %, respectively. The overall median survival was 48.9 months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10)., Conclusions: Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.

Objective: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the best treatment of several peritoneal surface malignancies. Isolated peritoneal recurrence may be treated by iterative procedures. The aim of this study was to evaluate immediate postoperative and long-term results after iterative CRS-HIPEC., Methods: From 1990 to 2010, 30 patients with isolated peritoneal recurrence underwent iterative procedures combining CRS-HIPEC., Results: Origins of peritoneal carcinomatosis were ovarian, colorectal, pseudomyxoma peritonei, peritoneal mesothelioma, gastric cancer, cholangiocarcinoma, leiomyosarcoma, and primary peritoneal serous carcinoma. Median recurrence-free survival (RFS) was 16.2 months from the first procedure. After the second procedure, one (3.3%) postoperative death occurred. Severe morbidity following the second procedure was 40% versus 30% after the first procedure (P = 0.37). At most recent follow up, 11 patients were disease-free, 10 were alive with recurrence, and 9 were dead with recurrence. Five-year overall survival after initial CRS with HIPEC was 65%, and overall median survival from diagnosis was 140 months., Conclusion: Iterative procedures combining CRS-HIPEC are feasible and allow long-term survival but may result in significant morbidity and mortality. Patients must be carefully selected, based on the following criteria: Origin of carcinomatosis, magnitude of first procedure, length of RFS, physiological age, co-morbidity, and possibility of complete cytoreduction., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now a recognized treatment for peritoneal carcinomatosis (PC). The objective of this phase I study is to determine the maximum tolerated dose of irinotecan (CPT-11) when used with mitomycin C (MMC) for closed abdomen HIPEC., Methods: Patients with PC fulfilling the inclusion criteria were studied. All underwent cytoreductive surgery and closed abdomen HIPEC with 0.7 mg/kg MMC and an escalating dose of irinotecan. Grade 4 (National Cancer Institute grading system) surgical and hematological complications were used to identify dose-limiting toxicity (DLT)., Results: 12 patients were studied. At the first dose level of irinotecan (100 mg/m(2)), one patient developed a grade 4 hematological toxicity. Three other patients were included at the same level with no toxicity. Three patients were then included at the second dose level (150 mg/m(2) irinotecan), of whom one developed a grade 4 surgical complication. Three further patients were thus included at the second dose level. Of these three, two patients developed DLT [grade 4 neutropenia in one, grade 4 neutropenia and thrombocytopenia with an intra-abdominal lymphatic fistula requiring reoperation (grade 4 surgical complication) in the other]. Dose escalation was stopped at this level. The maximum tolerated dose of irinotecan was determined to be 100 mg/m(2)., Conclusion: Closed HIPEC combining MMC and irinotecan is safe and feasible. For HIPEC, the maximum tolerated dose of irinotecan is 100 mg/m(2) when used with 0.7 mg/kg MMC.

Background: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) can improve survival in selected patients with primary or secondary peritoneal malignancies. With the opportunity for long-term survival, questions about the impact of those procedures in fertility in women of childbearing age can be raised., Materials and Methods: An international survey was performed among all teams participating in the International Peritoneal Surface Malignancy Group in order to collect data about pregnancies and their outcome in women having undergone previous CRS with adjuvant HIPEC., Results: There were 7 pregnancies reported after CRS and HIPEC in women treated for peritoneal malignancies. All these women conceived spontaneously, most of them within 2 years after the procedure. They delivered most often by vaginal way after an uneventful pregnancy. Their newborns were healthy, except 1 case of congenital diaphragmatic hernia requiring emergent surgery. There were 2 additional uneventful pregnancies reported after the diagnosis of pseudomyxoma peritonei and before CRS and HIPEC, with the support of the medical team. Another woman having undergone oocytes retrieval and embryo cryopreservation prior to the surgery was mother of twins after the procedure via a surrogate mother., Conclusion: Childbearing after cytoreductive surgery and heated intraperitoneal chemotherapy is possible in women conserving their genital organs after the procedure. The question of fertility should be considered and discussed in women in reproductive age prior to cytoreductive surgery and heated intraperitoneal chemotherapy. Different options could be offered in this setting. Multidisciplinary decision making involving surgical oncologists and fertility specialists is important.