Search Results (31)

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

Background: PIPAC is an innovative treatment that delivers low-dose aerosolized chemotherapy into the abdominal cavity of patients with peritoneal surface malignancies (PSMs). However, its role in the multimodal management of PSMs is unclear. Methods: We retrospectively analyzed data from 64 patients who underwent PIPAC for PSMs of a primary or secondary origin between June 2020 and December 2024 (median age of 64 years). Primary tumor sites included gastric (42.2%), colorectal (23.4%), ovarian cancer (21.9%), and others (12.5%). The median PCI was 15 (IQR 9–25), with ascites present in 60.9% of cases and a positive cytology in 48.4%. Results: A total of 82 PIPAC sessions were performed in 64 patients. The mean operation time was 96 min. Severe adverse events, defined as the Common Terminology Criteria for Adverse Events (CTCAE) of a grade ≥ 2, occurred in four patients (6.2%). The median hospital stay was 3 days, and systemic chemotherapy was resumed within 14 days after the procedure in 27 patients. Among the entire cohort, 37.5% received bidirectional therapy and 62.5% received palliative treatment, with a lower peritoneal cancer index (PCI) in the bidirectional group (9.5 vs. 23). The median overall survival (OS) was 32 months from diagnosis. Sixteen patients (25%) underwent two or more PIPAC sessions and showed an advantage in survival compared to patients who underwent only one procedure (3-year OS: 63.2% vs. 38.4%, p 0.030). Conversion surgery was achieved in 34.4%. Patients treated with a bidirectional intent demonstrated a longer OS (3-year: 66.0% vs. 33.9%, p 0.011). Colorectal and ovarian tumors exhibited better long-term outcomes compared to gastric cancer. Conclusions: PIPAC is a promising treatment for PSMs, with a low morbidity rate. Its favorable safety and short interval to systemic therapy resumption support its use as part of a bidirectional strategy. Full article

The peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Up to half of all patients that undergo curative-intent resection eventually develop peritoneal metastasis (PM), which accounts for significant morbidity and drives mortality. Despite recent advances in management, PM is associated with very poor prognosis, which is often measured in weeks to months. Clinical manifestations including bowel obstruction, ascites, and urinary obstruction have profound impact on quality of life. Even with relatively advanced disease, PM often remains occult on imaging and thus tend to be underdiagnosed and understudied. Many patients with peritoneal-only PM are excluded from clinical trials because response cannot be measured by standard radiographic criteria. Furthermore, as patients with PM are not eligible for surgical resection and low-volume peritoneal disease is often not amenable to percutaneous biopsy, tissue samples for peritoneal-specific translational studies are limited. Intraperitoneal therapeutics have been proposed as an attractive option for PM, as better penetration of tumor tissue can be achieved with less systemic toxicity compared with intravenous chemotherapy. Heated intraperitoneal chemotherapy (HIPEC), typically combined with cytoreductive surgery (CRS), is an option for select patients with PM from gynecologic or gastrointestinal primary, and for patients with primary peritoneal mesothelioma. However, the incorporation of locoregional therapy for PM in patients with PDAC has been poorly studied given the aggressive nature of pancreatic cancer and overall poor prognosis. With recent advances in existing treatment options, there may be a subset of patients who may derive benefits from locoregional control with cytoreduction and/or intraperitoneal chemotherapy. Critically, additional work is needed to determine PM-favorable clinical and tumoral predictive biomarkers to identify patients who may benefit from a more aggressive approach. We describe the current state of management of patients with peritoneal metastasis from PDAC and review the available data exploring peritoneal-directed therapy with cytoreductive surgery and/or intraperitoneal chemotherapy. Full article

Background/objectives: Despite the incremental improvement of survival with systemic therapy in metastatic gastric cancer (GC), the outcomes of patients with peritoneal carcinomatosis (PC) remain poor. The limited effectiveness of systemic therapy is attributed to the blood–peritoneal barrier and anarchic intra-tumoral circulation, which reduce the penetration of systemic therapy. Approaches that incorporate intraperitoneal (IP) chemotherapy, in addition to systemic therapies, may be a viable alternate strategy. Therefore, we provide a review of biology of gastric cancer peritoneal metastasis and evidence for bidirectional iterative IP chemotherapy in GCPC. Methods: A comprehensive search in PubMed, Scopus, Embase, Web of Science, Google Scholar, and ClinicalTrials.gov was performed to find the relevant articles and ongoing phase II/III clinical trials in iterative IP chemotherapy in GCPC. Results: Intraperitoneal (IP) chemotherapy leverages the blood–peritoneal barrier to allow for the administration of high concentrations of chemotherapy directly to the peritoneal metastases, with a significant reduction in the systemic toxicity and enhanced drug efficacy against peritoneal metastasis. This pharmacokinetic advantage of IP chemotherapy can be further enhanced by additional measures such as heat or aerosolization. There are three IP chemotherapy approaches, namely, heated intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosolized chemotherapy (PIPAC), and normothermic intraperitoneal chemotherapy (NIPEC). Recent evidence suggests that iterative IP chemotherapy combined with systemic therapy may offer significant survival benefits for patients with peritoneal metastasis. Furthermore, bidirectional treatment approaches may also increase the chances of surgical resection and survival. Conclusions: IP chemotherapy plays a pivotal role in the management of gastric carcinomatosis, particularly in combination with cytoreduction in highly selected patients. The combination of systemic and regional control may increase the chances of surgical resection and may ultimately lead to significant survival benefits. Full article

Background: Since 2011, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has emerged as a promising treatment option for patients with peritoneal surface malignancies (PSM) who are not eligible for cytoreductive surgery (CRS). Repeated minimal-invasive treatment is one of the key features and the current empirical standard treatment (ST) consists of at least three administrations over about three months. However, many patients are unable to complete the full course, limiting the potential benefits of PIPAC. Method: This retrospective, single-center study assessed the completion rate of ST and identified the main causes and predictive factors for discontinuation. This study also evaluated the feasibility, safety, and efficacy of PIPAC and investigated whether improved patient selection over the years has resulted in better oncological outcomes. Result: Data from 168 patients treated with PIPAC between January 2017 and March 2023 for a total of 336 procedures showed that only 29% completed ST. Multivariate analysis identified ascites >500 mL and a prior history of bowel obstruction as significant predictors of discontinuation. Conclusions: Patients with radiological or clinical signs of obstruction should not be considered for PIPAC treatment, and ascites increases the risk of incomplete treatment. Larger studies are eagerly awaited to corroborate these findings and refine the selection criteria by disease entity. Full article

Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC). Full article

Background: Advances in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have improved outcomes for selected patients with peritoneal surface malignancies (PSMs). Methods: This retrospective study analyzed 743 PSM patients treated at Fondazione Policlinico Universitario Agostino Gemelli from January 2016 to February 2024. The primary aim was to assess median overall survival (mOS), median disease-free survival (mDFS), and median progression-free survival (mPFS) stratified by tumor origin. Secondary outcomes examined the role of diagnostic laparoscopy in the management of PSMs and intra- and postoperative complications’ rates. Results: A total of 1113 procedures were performed: 389 CRS, 370 PIPAC, and 354 diagnostic laparoscopies. Colorectal cancer was the predominant indication for CRS (52.4%), with a mOS of 52 months and mDFS of 22 months. Patients affected by gastric cancer undergoing CRS had a mOS of 18 months and a mDFS of 13 months, while PIPAC yielded a mOS of 9 months and a mPFS of 4 months. Among patients with pseudomyxoma peritonei undergoing CRS, the 5-year DFS rate was 64.1%, and OS rate was 89%. Patients affected by mesothelioma and treated with CRS exhibited a median OS of 43 months and a DFS of 26 months. Pancreatic and hepatobiliary cancers were treated with PIPAC, with a respective mOS of 12 and 8 months. Postoperative complications occurred in 12.6% of CRS, 3.2% of PIPAC, and 1.7% of diagnostic laparoscopies. High peritoneal cancer index (PCI), gastric resection, and blood loss over 500 mL were identified as risk factors for major complications in a multivariate analysis. Conclusions: Developing a highly experienced multidisciplinary team is crucial for delivering tailored treatment strategies which aim to achieve optimal oncological outcomes while preserving patients’ quality of life. Full article

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) consists of the administration of aerosolized chemotherapy into the abdominal cavity of patients suffering from peritoneal carcinomatosis. Our aim was to review the evidence supporting PIPAC in patients with peritoneal carcinomatosis from colorectal cancer. Methods: A systematic review was performed in accordance with the 2020 PRISMA guideline. MEDLINE and CENTRAL were searched using combinations of terms including “Peritoneal carcinomatosis”, “Peritoneal metastasis”, “PIPAC”, “Pressurized intraperitoneal aerosol chemotherapy” and “Colorectal cancer”. Original studies, in English, including patients treated with PIPAC for colorectal peritoneal carcinomatosis, were considered eligible. Case reports, non-English or French language articles and secondary analyses were excluded. Results: A total of 385 articles were screened and 374 articles were excluded, leaving 11 publications for inclusion in the qualitative analysis. The included studies totalized 949 patients who received PIPAC for peritoneal carcinomatosis due to colorectal cancer. The median peritoneal carcinomatosis index (PCI) ranged from 10 to 31. In all studies, the complete PIPAC protocol was achieved with an average of two to three 3 PIPAC sessions per patient. Oxaliplatin (OX) was used as a chemotherapeutic agent in all studies and could be associated with intravenous 5-FU and leucovorin. Most post-operative adverse events were recorded as mild to moderate with no intraoperative complications. Only four studies reported a decrease in the average PCI score for 50% of the patients. Median overall survival ranged from 8 to 37.8 months. Quality of life indicators were stable between PIPAC-OX cycles with a small but not statistically significant trend of improvement of most functional scales. Conclusions: PIPAC for peritoneal carcinomatosis from colorectal origin is feasible, safe and tolerable. Its impact on survival outcomes or quality of life remains to be demonstrated by randomized trials. Full article

Background: Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. Methods: All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien–Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. Results: In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10–17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4–10). Conclusions: PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy. Full article

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. Full article

The peritoneum is a common site of metastases for gastrointestinal tumors that predicts a poor outcome. In addition to decreased survival, peritoneal metastases (PMs) can significantly impact quality of life from the resulting ascites and bowel obstructions. The peritoneum has been a target for regional therapies due to the unique properties of the blood–peritoneum barrier. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have become accepted treatments for limited-volume peritoneal disease in appendiceal, ovarian, and colorectal malignancies, but there are limitations. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) improves drug distribution and tissue penetration, allowing for a minimally invasive application for patients who are not CRS/HIPEC candidates based on high disease burden. PIPAC is an emerging treatment that may convert the patient to resectable disease, and may increase survival without major morbidity, as indicated by many small studies. In this review, we discuss the rationale and benefits of PIPAC, as well as sentinel papers describing its application for gastric, colorectal, appendiceal, and pancreatobiliary PMs. While no PIPAC device has yet met FDA approval, we discuss next steps needed to incorporate PIPAC into neoadjuvant/adjuvant treatment paradigms, as well as palliative settings. Data on active clinical trials using PIPAC are provided. Full article

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. Full article

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. Full article

The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers. Full article

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare form of mesothelioma that carries a very poor prognosis. The 5-year overall survival is about 20% (±5.9). Survival is optimal for patients suitable for cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC), with a median OS ranging from 34 to 92 months. However, selecting patients for surgery remains a complex task and requires a careful preoperative workup, rational analysis of prognostic profiles, and risk prediction models. Systemic chemotherapy could be offered: (1) in the adjuvant setting for high-risk patients; (2) for patients not eligible for CRS; and (3) for those with recurrent disease. It mainly includes the combination of Platin compound with Pemetrexed or immunotherapy. The biology of DMPM is still largely unknown. However, progress has been made on some fronts, such as telomere maintenance mechanisms, deregulation of apoptosis, tyrosine kinase pathways, and mutation of BRCA1-associated protein 1 (BAP1). Future perspectives should include translational research to improve our understanding of the disease biology to identify druggable targets. We should also clear the role of immune checkpoint inhibitors and investigate new locoregional technologies, such as pressurized intraperitoneal aerosol chemotherapy (PIPAC) or normothermic intraperitoneal chemotherapy (NIPEC). Full article