Efficacy and safety of intraperitoneal chemotherapy for pancreatic cancer.

Pancreatic cancer is a highly aggressive cancer with unfavorable prognosis despite the therapeutic interventions. Intraperitoneal chemotherapy has recently shown potential outcomes in the presence of peritoneal metastases. However, a consensus is still lacking on different methods for intraperitoneal chemotherapy in pancreatic cancer. A variety of drugs and doses via three types of intraperitoneal chemotherapy have been studied. The prognosis and treatment strategies for pancreatic ductal adenocarcinoma (PDAC) will be significantly influenced by peritoneal dissemination and resectability of the macroscopic disease. Normothermic intraperitoneal chemotherapy (NIPEC) has been used for the treatment of peritoneal metastases of pancreatic carcinomas. Intraperitoneal chemotherapy is often combined with systemic therapies or surgical procedures which may lead to favorable combination therapies such as cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a relatively new approach that provides a homogenous and deep penetration of the chemotherapy into the peritoneum by producing aerosols. The present study aims to review the literature for recent evidence on intraperitoneal chemotherapy in pancreatic cancer.

Management of Peritoneal Surface Malignancies in Saudi Arabia: An Update.

Peritoneal surface malignancies (PSM) are aggressive and associated with poor prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used to treat PSM since 1990. In Saudi Arabia, the first HIPEC and pressurized intraperitoneal aerosol chemotherapy (PIPAC) were performed in 2008 and 2019, respectively. With increasing incidences of PSM in Saudi Arabia, the demand for such procedures has grown. This article outlines the status of PSM management in Saudi Arabia and its prospects.

Outcome of patients with peritoneal metastasis from ovarian cancer treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).

Objectives: There are few data on Pressurized IntraPeritoneal Aerosol Chemotherapy with cisplatin and doxorubicin (PIPAC C/D) in women with primary unresectable or recurrent platinum-resistant peritoneal metastasis (PM) from ovarian cancer (OC). We evaluated survival, histological and cytological response, Quality of Life (QoL) and toxicity after PIPAC C/D in these patients. Methods: Retrospective analysis of patients from the prospective PIPAC-OPC1 and -OPC2 studies. The histological response was evaluated by the Peritoneal Regression Grading Score (PRGS). QoL questionnaires were collected at baseline and after third PIPAC or 60 days. Adverse events were collected until 30 days after the last PIPAC. Demographic and survival data were analysed based on intention to treat. Response, QoL and toxicity were analysed per protocol (≥1 PIPAC). Results: Twenty-nine patients were included. Five patients (17 %) were non-accessible at PIPAC 1. One patient was excluded due to liver metastases at PIPAC 1. Thus, 23 patients had 76 PIPACs (median 2, range 1-12). Median overall survival was 8.2 months (95 % CI 4.4-10.3) from PIPAC 1. Biopsy data were available for 22 patients, and seven (32 %) patients had a major/complete histological response (PRGS≤2) at PIPAC 3. No cytological conversions were registered. Symptoms and function scores worsened, while emotional scores improved. Three patients had severe adverse reactions (two ileus, one pulmonary embolism); no life-threatening reactions or treatment-related mortality was observed. Conclusions: PIPAC C/D was feasible and induced histological regression in a substantial proportion of patients with platinum-resistant PM from OC. Larger studies are needed to evaluate impact on survival.

RNA expression profiling of peritoneal metastasis from pancreatic cancer treated with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Objectives: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an experimental treatment option in peritoneal metastasis from pancreatic cancer (PM-PC). Aims were to examine mRNA profile of fibrosis due to response after systemic chemotherapy and PIPAC (Regression) compared to treatment-naïve PM-PC and chronic cholecystitis-related peritoneal fibrosis (Controls). Methods: Peritoneal biopsies (PBs) from PM-PC patients who had undergone systemic chemotherapy and PIPAC were evaluated with Peritoneal Regression Grading Score (PRGS). We extracted RNA from PBs with Regression (PRGS 1, n=11), treatment-naïve PM-PC (n=10), and Controls (n=10). Profiling of 800 mRNAs was performed (NanoString nCounter, PanCancer Immuno-Oncology 360 (IO-360) and 30 additional stroma-related mRNAs). Results: Regression vs. PM-PC identified six up-regulated and 197 down-regulated mRNAs (FDR≤0.05), linked to TNF-α signaling via NF-kB, G2M checkpoint, epithelial-mesenchymal transition, estrogen response, and coagulation. Regression vs. Controls identified 43 significantly up-regulated mRNAs, linked to interferon-α response, and down-regulation of 99 mRNAs, linked to TNF-α signaling via NF-kB, inflammatory response, epithelial-mesenchymal transition, KRAS signaling, and hypoxia (FDR≤0.05). Conclusions: In regressive fibrosis of PM-PC after systemic chemotherapy and PIPAC (Regression), downregulation of mRNAs related to key tumor biological pathways was identified. Regression also showed transcriptional differences from unspecific, benign fibrosis (Controls). Future studies should explore whether mRNA profiling of PBs with PM from PC or other primaries holds prognostic or predictive value.

Efficacy and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in ovarian cancer: a systematic review of current evidence.

BACKGROUND: PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis. A systematic review was conducted to assess current evidence on the efficacy and outcomes of PIPAC in patients affected by ovarian cancer. METHODS: The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched up to December 2023. Studies reporting data on patients with OC treated with PIPAC were included in the qualitative analysis. RESULTS: Twenty-one studies and six clinical trials with 932 patients who underwent PIPAC treatment were identified. The reported first access failure was 4.9%. 89.8% of patients underwent one, 60.7% two and 40% received three or more PIPAC cycles. Pathological tumour response was objectivated in 13 studies. Intra-operative complications were reported in 11% of women and post-operative events in 11.5% with a 0.82% of procedure-related mortality. Quality of life scores have been consistently stable or improved during the treatment time. The percentage of OC patients who became amenable for cytoreductive surgery due to the good response after PIPAC treatment for palliative purposes is reported to be 2.3%. CONCLUSION: The results showed that PIPAC is safe and effective for palliative purposes, with a good pathological tumour response and quality of life. Future prospective studies would be needed to explore the role of this treatment in different stages of the disease, investigating a paradigm shift towards the use of PIPAC with curative intent for women who are not eligible for primary cytoreductive surgery.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in the Treatment of Gastric Cancer: Feasibility, Efficacy and Safety-A Systematic Review and Meta-Analysis.

Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging technique for delivering chemotherapy directly to the peritoneum via a pressurized aerosol. Its growing attention stems from its effectiveness in treating peritoneal carcinomatosis (PC) originating from various primary tumors, with gastric cancer (GC) being among the most prevalent. This study aimed to systematically investigate PIPAC's therapeutic role in gastric cancer peritoneal metastasis (GCPM). Methods: The systematic review and meta-analysis followed the PRISMA 2020 guidelines, searching Pubmed, Web of Science, and SCOPUS databases. The meta-analysis of relative risks and mean differences compared patients undergoing one or two PIPAC sessions with those completing three or more, assessing various outcomes. Results: Eighteen studies underwent qualitative analysis, and four underwent quantitative analysis. Patients with three or more PIPAC procedures had shorter hospital stays (MD = -1.2; 95%CI (-1.9; -0.5); p < 0.001), higher rates of histopathological response (RR = 1.77, 95%CI 1.08; 2.90; p = 0.023), and significantly improved overall survival (MD = 6.0; 95%CI 4.2; 7.8; p < 0.001). Other outcomes showed no significant differences. Conclusions: PIPAC demonstrated efficacy in carefully selected patients, enhancing histopathologic response rates and overall survival without prolonging hospital stays. This study underscores the necessity for randomized controlled trials and precise selection criteria to refine PIPAC's implementation in clinical practice.

First Clinical Safety and Feasibility Data of Whole-body Hyperthermia Pressurized Intraperitoneal Aerosol Chemotherapy (WBH-PIPAC) for Peritoneal Surface Malignancies.

BACKGROUND/AIM: This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal surface malignancies. PATIENTS AND METHODS: This study retrospectively analyzed a database of 28 patients who had received one cycle of normothermic PIPAC prior to repetitive WBH-PIPACs. WBH (39-40°C) was induced using a Water-filtered infrared A device. Doxorubicin plus cisplatin or oxaliplatin was nebulized into a constant capnoperitoneum of 20 mmHg for 30 min at doses of 6.0 mg, 30.0 mg, or 120 mg per m2 body surface area, respectively. The primary outcome measures were feasibility and perioperative complications. RESULTS: The median age was 62 years (range=45-78 years). Primary tumor sites included the upper gastrointestinal tract (n=9), colon/rectum (n=7), hepato-pancreato-biliary system (n=3), peritoneum (n=2), ovaries (n=2), and unknown primary (n=5). The induction of WBH failed in one patient (6 liters ascites). After a median warming period of 95 min (53-117 min), the median rectal temperature (Trec) was 39.5°C (39.2-39.9°C). No hyperthermia-related side effects were observed. Twenty-seven patients received 50 WBH-PIPACs. The median time of therapeutic capnoperitoneum and treatment time with Trec ≥39°C was 39 min (37-43 min) and 66 min (53-69 min), respectively. The overall rate of postoperative procedure-related complications was 9/50, including seven grade I and two grade II complications. There were no grade III-V complications. CONCLUSION: In a highly selected group of patients, the feasibility and perioperative safety of WBH-PIPAC was comparable to normothermic PIPAC.

Hyperthermic pressurized intraperitoneal aerosol drug delivery system in a large animal model: a feasibility and safety study.

BACKGROUND: We developed a novel drug delivery system called hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) that hybridized Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). The present study aims to assess the feasibility and safety of HPIPAC system in a large animal survival model. METHODS: Eleven pigs (eight non-survival models and three survival models) were used in the experiment. The heat module in the HPIPAC controller circulates hyperthermic CO2 in a closed-loop circuit and creates gas-based dry intraperitoneal hyperthermia. Three 12 mm trocars were placed on the abdomen. The afferent CO2 tube wound with heat generating coil was inserted into a trocar, and the efferent tube was inserted into another trocar. Heated CO2 was insufflated and circulated in a closed circuit until the intra-abdominal and peritoneal surface temperature reached 42 °C. 100 ml of 5% dextrose in water was nebulized for 5 min and the closed-loop circulation was resumed for 60 min at 42 °C. Tissue biopsies were taken from several sites from the pigs in the survival model. RESULTS: The average change in core temperature of the pigs was 2.5 ± 0.08 °C. All three pigs displayed no signs of distress, and their vital signs remained stable, with no changes in their diet. In autopsy, inflammatory and fibrotic responses at the biopsy sites were observed without serious pathologic findings. CONCLUSIONS: We successfully proved the feasibility and safety of our novel HPIPAC system in an in-vivo swine survival model.

The Future of Interventions for Stage IV Colorectal Cancers.

Future options for the management of stage IV colorectal cancer are primarily focused on personalized and directed therapies. Interventions include precision cancer medicine, utilizing nanocarrier platforms for directed chemotherapy, palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC), adjunctive oncolytic virotherapy, and radioembolization techniques. Comprehensive genetic profiling provides specific tumor-directed therapy based on individual genetics. Biomimetic magnetic nanoparticles as chemotherapy delivery systems may reduce systemic side effects of traditional chemotherapy by targeting tumor cells and sparing healthy cells. PIPAC is a newly emerging option for patients with peritoneal metastasis from colorectal cancer and is now being used internationally, showing promising results as a palliative therapy for colorectal cancer. Oncolytic virotherapy is another emerging potential treatment option, especially when combined with standard chemotherapy and/or radiation, as well as immunotherapy. And finally, radioembolization with yttrium-90 ( 90 Y) microspheres has shown some success in treating patients with unresectable liver metastasis from colorectal cancer via selective arterial injection.

Gastric cancer with peritoneal metastases: a single center outline and comparison of different surgical and intraperitoneal treatments.

INTRODUCTION: Gastric cancer with peritoneal metastasis (GCPM) has an unfavourable prognosis. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are promising treatment options that have been shown to improve survival. The aim of this study was to assess the impact of different treatments such as systemic chemotherapy, systemic chemotherapy + PIPAC, and CRS + HIPEC in patients with GCPM. MATERIAL AND METHODS: This single-centre retrospective study included 82 patients with GCPM treated between January 2016 and June 2021. After first-line chemotherapy, depending on disease response and burden, the patients were divided into three treatment groups: chemotherapy alone, chemotherapy + PIPAC, and CRS + HIPEC. The primary outcome was overall survival (OS) from diagnosis, which was compared among the treatment groups. RESULTS: Thirty-seven (45.1%) patients were administered systemic chemotherapy alone, 25 (30.4%) received chemotherapy + PIPAC, and 20 (24.4%) underwent CRS + HIPEC. The CRS + HIPEC group had better OS (median 24 months) than the PIPAC group (15 months, p = 0.01) and chemotherapy group (5 months, p = 0.0001). Following CRS + HIPEC, the postoperative grade 3-4 complication rate was 25%, and no postoperative in-hospital deaths occurred. The median disease-free survival (DFS) was 12 months. Multivariate analysis identified peritoneal carcinomatosis index (PCI) > 7 as an independent predictor of worse DFS. No independent predictors of OS were identified. CONCLUSION: Among patients with GCPM, we identified a highly selected population with oligometastatic disease. In this group, CRS + HIPEC provided a significant survival advantage with an acceptable major complication rate compared with other available therapies (systemic chemotherapy alone or in combination with PIPAC).

Pressurized intraperitoneal aerosol chemotherapy, reasons for interrupting treatment: a systematic review of the literature.

Objectives: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) gives encouraging results in the treatment of peritoneal metastasis (PM). The current recommendations require at least 3 sessions of PIPAC. However, some patients do not complete the full treatment course and stop after only 1 or 2 procedures, hence the limited benefit. A literature review was performed, with search terms including "PIPAC" and "pressurised intraperitoneal aerosol chemotherapy." Content: Only articles describing the causes for premature termination of the PIPAC treatment were analysed. The systematic search identified 26 published clinical articles related to PIPAC and reporting causes for stopping PIPAC. Summary: The series range from 11 to 144 patients, with a total of 1352 patients treated with PIPAC for various tumours. A total of 3088 PIPAC treatments were performed. The median number of PIPAC treatments per patient was 2.1, the median PCI score at the time of the first PIPAC was 19 and the number of patients who did not complete the recommended 3 sessions of PIPAC was 714 (52.8%). Disease progression was the main reason for early termination of the PIPAC treatment (49.1%). The other causes were death, patients' wishes, adverse events, conversion to curative cytoreductive surgery and other medical reasons (embolism, pulmonary infection, etc…). Outlook: Further investigations are necessary to better understand the causes for interrupting PIPAC treatment and also improving the selection of patients who are most likely to benefit from PIPAC.

The role of cytology in patients undergoing pressurized intraperitoneal aerosol chemotherapy (PIPAC) treatment for peritoneal carcinomatosis.

Objectives: Cytology of ascites or peritoneal washing is a routine part of staging of peritoneal metastases (PM). We aim to determine value of cytology in patients undergoing pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods: Single-center retrospective cohort study included consecutive patients having PIPAC for PM of different primary between January 2015 and January 2020. Results: A total of 75 patients (median 63 years (IQR 51-70), 67 % female) underwent a total of 144 PIPAC. At PIPAC 1 59 % patients had positive and 41 % patients had negative cytology. Patients with negative and positive cytology only differed in terms of symptoms of ascites (16% vs. 39 % respectively, p=0.04), median ascites volume (100 vs. 0 mL, p=0.01) and median PCI (9 vs. 19, p<0.01). Among 20 patients who completed 3 PIPACs (per protocol), cytology changed in one from positive to negative, and in two from negative to positive. Median overall survival was 30.9 months in the per protocol group and 12.9 months in patients having <3 PIPACs (=0.519). Conclusions: Positive cytology under PIPAC treatment is more frequently encountered in patients with higher PCI and symptomatic ascites. Cytoversion was rarely observed and cytology status had no impact on treatment decisions in this cohort.

Occupational Exposure during Intraperitoneal Pressurized Aerosol Chemotherapy Using Doxorubicin in a Pig Model.

Background: This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. Methods: All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. Results: Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48-5.44 ng/cm2 and the trocar showed 0.98 ng/cm2 in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm2, following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. Conclusions: Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.

Gastric Cancer (GC) with Peritoneal Metastases (PMs): An Overview of Italian PSM Oncoteam Evidence and Study Purposes.

Gastric cancer (GC) continues to be one of the leading types of malignancies worldwide, despite an ongoing decrease in incidence. It is the fifth most frequent type of cancer in the world and the fourth leading cause of cancer death. Peritoneal metastases (PMs) occur in 20-30% of cases during the natural history of the disease. Systemic chemotherapy (SC) is undoubtedly the standard of care for patients with GC and PMs. However, with the development of highly effective regimens (SC combined with intraperitoneal chemotherapy), significant tumor shrinkage has been observed in many patients with synchronous GC and PMs, allowing some to undergo curative resection "conversion surgery" with long-term survival. In recent years, there has been growing interest in intraperitoneal chemotherapy for PMs, because the reduced drug clearance associated with the peritoneal/plasma barrier allows for direct and prolonged drug exposure with less systemic toxicity. These procedures, along with other methods used for peritoneal surface malignancies (PSMs), can be used in GCs with PMs as neoadjuvant chemotherapy or adjuvant treatments after radical surgery or as palliative treatments delivered either laparoscopically or-more recently-as pressurized intraperitoneal aerosol chemotherapy. The great heterogeneity of patients with stage IV gastric cancer did not allow us to carry out a systemic review; therefore, we limited ourselves to providing readers with an overview to clarify the indications and outcomes of integrated treatments for GCs with PMs by analyzing reports from the international clinical literature and the specific experiences of our oncoteam.

10 Years of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): A Systematic Review and Meta-Analysis.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. METHODS: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman-Tukey double arcsine transformation, and 95% CIs were calculated using Clopper-Pearson exact CIs in all instances. RESULTS: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3-4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61-0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. CONCLUSIONS: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets.

Response Evaluation in Patients with Peritoneal Metastasis Treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) directed therapy emerged as a treatment of peritoneal metastasis (PM) a decade ago. The response assessment of PIPAC is not uniform. This narrative review describes non-invasive and invasive methods for response evaluation of PIPAC and summarizes their current status. PubMed and clinicaltrials.gov were searched for eligible publications, and data were reported on an intention-to-treat basis. The peritoneal regression grading score (PRGS) showed a response in 18-58% of patients after two PIPACs. Five studies showed a cytological response in ascites or peritoneal lavage fluid in 6-15% of the patients. The proportion of patients with malignant cytology decreased between the first and third PIPAC. A computed tomography showed stable or regressive disease following PIPAC in 15-78% of patients. The peritoneal cancer index was mainly used as a demographic variable, but prospective studies reported a response to treatment in 57-72% of patients. The role of serum biomarkers of cancer or inflammation in the selection of candidates for and responders to PIPAC is not fully evaluated. In conclusion, response evaluation after PIPAC in patients with PM remains difficult, but PRGS seems to be the most promising response evaluation modality.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal surface malignancies (PSM): a prospective single-center registry study.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new, palliative approach for patients with peritoneal surface malignancies (PSMs). Its main goals are to control symptoms and ascites. For this experimental procedure, treatment efficacy and patient safety need to be closely monitored. METHODS: We performed a prospective registry study for patients with PSMs. Cisplatin (C) (7.5 mg/m2 body surface) and doxorubicin (D) (1.5 mg/m2) were administered laparoscopically via PIPAC. RESULTS: Between November 2015 and June 2020, we recorded data from 108 patients and 230 scheduled procedures. Tumor burden, patient fitness, quality of life, operating time and in-hospital stay remained stable over consecutive procedures. We recorded 21 non-access situations and 14 intraoperative complications (11 intestinal injuries, and three aspirations while inducing anesthesia). Three or more previous abdominal surgeries or cytoreductive surgery (CRS) with intraperitoneal hyperthermic chemoperfusion (HIPEC) were risk factors for non-access and intestinal injuries (χ2, p ≤ 0.01). Five Grade IV and three Grade V postoperative complications according to the Clavien-Dindo Classification (CDC) occurred. Median overall survival was 264 days (interquartile range 108-586). Therapies were primarily discontinued because of death (34%), progressive (26%), or regressive (16%) disease. CONCLUSION: PIPAC is effective in stabilizing PSMs and retaining quality of life in selected patients. Earlier abdominal surgeries and CRS with HIPEC should be considered when determining the indication for PIPAC. Randomized controlled studies are needed to evaluate PIPAC's therapeutic benefits compared to systemic chemotherapy (sCHT) alone. TRIAL REGISTRATION: NCT03100708 (April 2017).

Hospitalization cost of Pressurized Intraperitoneal Aerosol chemotherapy (PIPAC).

INTRODUCTION: Pressurized Intraperitoneal Aerosol chemotherapy (PIPAC) is a new surgical technique for the treatment of unresectable peritoneal carcinomatosis. Very little data is available on the costs of this treatment in France as there is currently no code for PIPAC in the French Common Classification of Medical Acts (CCAM). Our objective was to estimate the mean cost of hospitalization for PIPAC in two French public teaching hospitals. METHODS: The mean cost of hospitalization was estimated from the mean fixed-rate remuneration paid to the hospital and the mean additional costs of treatment paid by the hospital. At discharge a patient's hospitalization is classified into a diagnosis related group, which determines the fixed-rate remuneration paid to the hospital (obtained from the national hospitals database - PMSI). Costs of medical devices and drug treatments specific to PIPAC, not covered by the fixed-rate remuneration, were obtained from the hospital pharmacies. RESULTS: Between July 2016 and November 2021, 205 PIPAC procedures were performed on 79 patients (mean procedures per patient = 2.6). Mean operating room occupancy was 165 min. The mean fixed-rate remuneration received by the hospitals per PIPAC hospitalization was €4031. The actual mean cost per hospitalization was €6562 for a mean length-of-stay of 3.3 days. Thus, each PIPAC hospitalization cost the hospital €2531 on average. CONCLUSION: The current reimbursement of PIPAC treatment by the national health system is insufficient and represents only 61% of the real cost. The creation of a new fixed-rate remuneration for PIPAC taking into account this cost differential is necessary.

Oncological Outcomes After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in the Treatment of Peritoneal Carcinomatosis.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique for the treatment of initially unresectable peritoneal carcinomatosis (PC). Our objective was to assess its oncological outcomes. METHODS: Between July 2016 and September 2020, data from 100 PIPAC procedures with oxaliplatin or doxorubicin-cisplatin in 49 patients with PC (all etiologies) were analyzed. We studied the evolution of the peritoneal cancer index (PCI), the need for radical surgery (R0), and overall survival (OS). RESULTS: The patients' median age was 65 (59; 71) years, and 55.1% were women. Median PIPAC procedures per patient were 2 (1-3), and 28 (57.1%) underwent more than one PIPAC procedure. Median PCI at the first PIPAC was 19 (15-22). PCI decreased for 37%, remained stable for 29.6%, and increased for 33.4% patients. Four (8.3%) underwent radical R0 surgery after PIPAC. After a median follow-up of 16.1 months (1.5-90.1), the median overall survival from PC diagnosis was 29.1 months (14.8-34.3), with a median gastric and colorectal PC survival of 11.3 (7.2-34.3) and 29.1 months (16.1-31) respectively. Overall survival after the first PIPAC session was 11.6 months (6-17.3), with median survival after gastric and colorectal PCs being 6 (2.9-15.5) and 13.3 months (5-17.6), respectively. Stratification of patients according to the number of lines of systemic chemotherapy, PIPAC procedures, and the chronology of PC onset did not result in a significant difference in survival. CONCLUSION: The OS was in line with the literature. PIPAC could delay oncological progression and improve survival. These encouraging results justify the ongoing and future evaluations of PIPAC by prospective randomized trials.

Peritoneal regression grading score (PRGS) in peritoneal metastasis: how many biopsies should be examined?

Objectives: The four-tied peritoneal regression grading score (PRGS) is increasingly used to evaluate the response of peritoneal metastases (PM) to chemotherapy. The minimal number of peritoneal biopsies needed for PRGS determination remains unclear. Methods: A prospective cohort of 89 PM patients treated with 210 pressurized intraperitoneal aerosol chemotherapy (PIPAC) cycles was investigated. Four biopsies from every abdominal quadrant were recommended. Histological tumor response was defined as a stable or decreasing mean PRGS between therapy cycles, progression increasing. We compared the diagnostic uncertainty induced by missing biopsies to the histological response. Results: A total of 49 patients had at least two PIPAC and were eligible for therapy response assessment. Mean PRGS decreased from 2.04 (CI 5-95% 1.85-2.27) to 1.79 (CI 5-95% 1.59-2.01), p=0.14, as a proof of therapy effectiveness. 35 (71.4%) patients had a stable or decreasing PRGS (therapy response), 14 (28.6%) a PRGS increase (disease progression). Histology showed agreement between four biopsies in 42/210 laparoscopies (20%), between ≥3 biopsies in 103 (49%), and between ≥2 biopsies in 169 laparoscopies (81%). Mean loss of information with one missing biopsy was 0.11 (95% CI=0.13) PRGS points, with two missing biopsies 0.18 (95% CI 0.21). In 9/49 patients (18.3%), the loss of information with one less biopsy exceeded the change in PRGS under therapy. Conclusions: A minimum of three biopsies is needed to diagnose PM progression with an accuracy superior to 80%. Missing biopsies often result in a false diagnosis of tumor progression.