Treatment Of Peritoneal Carcinomatosis Research Articles

Triple-regulated conditionally replicating adenovirus for effective and safer treatment of peritoneal carcinomatosis

There is no effective therapy for peritoneal carcinomatosis derived from gastric cancer. An ideal conditionally replicating adenovirus (CRA) that selectively replicates in and kills cancer cells has not been developed for gastric cancer-derived peritoneal carcinomatosis. Using our platform technology of CRA regulated and treating tumors with multiple factors (m-CRA), we generated two types of survivin-responsive m-CRAs, Surv.m-CRA-CMVp and Surv.m-CRA-CEAp, consisting of E1A downstream of the survivin promoter, and the mutated E1B gene downstream of the human cytomegalovirus immediate early gene enhancer/promoter and carcinoembryonic antigen promoter, respectively. Survivin mRNA was expressed at high and undetectable levels in two gastric cancer cells and eleven normal cells, respectively. Carcinoembryonic antigen was expressed at high and very low levels in MKN-45 gastric cancer and normal PrEC cells, respectively, and was not detected in other cell types. While both Surv.m-CRA-CEAp and Surv.m-CRA-CMVp exhibited potent cytotoxic effects on MKN-45 cells in vitro, Surv.m-CRA-CEAp significantly reduced cytotoxicity to normal cells compared to Surv.m-CRA-CMVp. Control mice that received an intraperitoneal injection of MKN-45 cells gradually lost body weight and died of peritoneal carcinomatosis within 98 days. In contrast, all mice receiving Surv.m-CRA-CEAp or Surv.m-CRA-CMVp-infected MKN-45 cells increased their body weight and survived 120 days. In conclusion, the triple-regulated Surv.m-CRA-CEAp enhances cancer specificity (i.e., safety) without reducing the potent therapeutic effect for carcinoembryonic antigen-positive gastric cancer-derived peritoneal carcinomatosis. The modified E1B promoter strategy of CRA facilitates the development of novel CRAs for the effective and safe treatment of a variety of refractory cancers.

Targeting vascular disrupting agent-treated tumor microenvironment with tissue-penetrating nanotherapy

Cancer treatment with vascular disrupting agents (VDAs) causes rapid and extensive necrosis in solid tumors. However, these agents fall short in eliminating all malignant cells, ultimately leading to tumor regrowth. Here, we investigated whether the molecular changes in the tumor microenvironment induced by VDA treatment sensitize the tumors for secondary nanotherapy enhanced by clinical-stage tumor penetrating peptide iRGD. Treatment of peritoneal carcinomatosis (PC) and breast cancer mice with VDA combretastatin A-4 phosphate (CA4P) resulted in upregulation of the iRGD receptors αv-integrins and NRP-1, particularly in the peripheral tumor tissue. In PC mice treated with CA4P, coadministration of iRGD resulted in an approximately threefold increase in tumor accumulation and a more homogenous distribution of intraperitoneally administered nanoparticles. Notably, treatment with a combination of CA4P, iRGD, and polymersomes loaded with a novel anthracycline Utorubicin (UTO-PS) resulted in a significant decrease in the overall tumor burden in PC-bearing mice, while avoiding overt toxicities. Our results indicate that VDA-treated tumors can be targeted therapeutically using iRGD-potentiated nanotherapy and warrant further studies on the sequential targeting of VDA-induced molecular signatures.

How to Implement Pressurized Intraperitoneal Aerosol Chemotherapy into a National Health System Scenario: A Single-Center Retrospective Analysis of Costs and Economic Sustainability at a High-Volume Italian Hospital.

PIPAC is a new surgical procedure and a viable treatment option for PSM patients, due to promising therapeutic outcomes, minimal invasiveness, limited surgical morbidity, and systemic toxicity side effects. However, its implementation throughout hospitals is hard to obtain due to its fragile economical sustainability. A retrospective health economic analysis was conducted in order to evaluate the cost of hospitalization for patients undergoing PIPAC treatment at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, in Rome. The average cost of a PIPAC procedure was defined based on the cost of surgery (cost of surgical material, operating room, intraperitoneal chemotherapy), hospital stay, diagnostic examinations, and drugs used during the stay. A total of 493 PIPAC procedures were performed on 222 patients with peritoneal metastases or primary peritoneal cancer from 2017 to 2023. Since the mean remuneration for each PIPAC hospitalization is €5916 and the mean expenditure per hospitalization is €6538, this results in an operating profit per PIPAC hospitalization of -€622. The reimbursement of PIPAC treatment by the Italian National Health System currently only partially covers the hospital's costs. Development of specific codes and adequate reimbursement for PIPAC by recognizing this procedure as a proper treatment for peritoneal carcinomatosis is essential.

Photodynamic theranostics in surgical treatment of patients with peritoneal carcinomatosis

The role and possibilities of photodynamic theranostics, including fluorescence diagnostics and photodynamic therapy, in complex cytoreductive surgical treatment of peritoneal carcinomatosis, evaluation of the effectiveness of its use, and analysis of the impact of this approach on the results of surgical intervention were investigated. Available modern domestic and foreign scientific literature were analyzed using PubMed, eLibrary.ru, and Google Scholar. Peritoneal carcinomatosis is characterized by the spread of tumor cells in the peritoneum and can be either a primary form of a tumor, such as pseudomyxoma and mesothelioma, or metastatic spread of cancer, most often of the gastrointestinal tract or gynecological organs. Surgical treatment of peritoneal carcinomatosis is crucial in the complex treatment of this category of patients, which determines the importance of further improvement of cytoreductive technologies. The extent of peritoneal dissemination during surgery may be underestimated, since intraoperative diagnosis is based solely on visual inspection and palpation. Thus, the use of phototheranostics — fluorescence diagnostics and photodynamic therapy — is a promising direction that has an antitumor effect and visualizes the peritoneum involved in the oncological process, which is beneficial for determining the required volume of peritonectomy. Currently, they are promising methods in the treatment of tumors of various locations. Both techniques are linked by the principle of theranostics (including diagnosis of the disease and personalized treatment of the patient) and imply the use of specific dyes (photosensitizers) and their ability to be excited under the influence of light of a certain wavelength. The therapeutic and diagnostic potential of phototheranostics in the complex surgical treatment of peritoneal carcinomatosis is emphasized; the main problems are described and prospects for the development of this technology are presented based on retrospective and prospective studies and systematic reviews.

Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to Folic Acid Analog induces Ovarian Tumor Cell Death and inhibits IL-6-mediated Inflammation

Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the development of new therapies. Indeed, our main objective is to develop a targeted photodynamic therapy (PDT) treatment of peritoneal carcinomatosis from OC to improve the life expectancy of cancer patients. Herein, we propose a targeted-PDT using a vectorized photosensitizer (PS) coupled with a newly folic acid analog (FAA), named PSFAA, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis.This PSFAA was the result of the coupling of pyropheophorbide-a (Pyro-a), as the PS, to a newly synthesized FAA via a polyethylene glycol (PEG) spacer. The selectivity and the PDT efficacy of PSFAA was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα.Final PSFAA, including the synthesis of a newly FAA and its conjugation to Pyro-a, was obtained after 10 synthesis steps, with an overall yield of 19%. Photophysical properties of PSFAA in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φf = 0.39 and ΦΔ = 0.53 for free Pyro-a, and Φf = 0.26 and ΦΔ = 0.41 for PSFAA). Any toxicity of PSFAA was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PSFAA on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6).This new PSFAA has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.

Ex vivo assessment of cellular mass response for personalized therapy selection of hyperthermic intraperitoneal chemotherapy (HIPEC) agents.

3132 Background: Despite progress in the development of HIPEC protocols for the treatment of peritoneal carcinomatosis, agent selection remains largely empiric with few biomarkers for guiding treatment. Ex vivo assessment of drug response using single-cell mass measurements offers a promising option for therapy selection. Previously, we have shown that mass response testing (MRT) is a malignancy- and drug-agnostic means of assessing drug response (1) and can predict a patient’s clinical response to therapy in a range of solid and hematological malignancies (2). Methods: Tissue specimens were collected from patients with peritoneal carcinomatosis as part of an ancillary study for a HIPEC clinical trial (NCT04847063) to explore the feasibility of performing MRT with these specimen types. Briefly, after overnight shipment of viable tumor tissue, tumor cells were isolated and treated with various therapies ex vivo. Single-cell mass distributions of vehicle and drug-treated populations were compared to determine the functional activity of each agent. Results: MRT was attempted for 60 patients with metastatic disease, 10 of whom had peritoneal carcinomatosis and ultimately received HIPEC. The HIPEC cases included histologies such as peritoneal mesothelioma (n=4), colorectal cancer (n=3), ovarian cancer (n=2), and small bowel adenocarcinoma (n=1). In total, 8 out of 10 peritoneal specimens had a sufficiently high tumor cell count, viability, and purity to perform MRT. These specimens displayed clear and statistically distinguishable mass response patterns of response and non-response to several different agents commonly used for HIPEC treatment such as cisplatin, oxaliplatin, doxorubicin, and mitomycin C. Study design:These feasibility results serve as the foundational data for launching a single-site phase II interventional study at the NCI’s Center for Cancer Research. The study will evaluate the potential benefit of personalized treatment regimens determined by MRT for patients with peritoneal carcinomatosis, particularly mesothelioma, a context where therapeutic options have relative equipoise in clinical efficacy. Tumor biopsies will be obtained via laparoscopy prior to HIPEC and submitted to a CLIA-certified lab for MRT to assess the responses of various clinically acceptable agents. The HIPEC regimen will be selected based on these MRT results returned within two days of sample collection. Enrolled patients will then undergo cytoreduction and HIPEC, and progression-free and overall survival will be monitored. As a single-arm, non-randomized trial, patient responses will be compared with a matched synthetic control to assess the impact of MRT on efficacy of HIPEC regimens. Conclusions: MRT is feasible for peritoneal carcinomatosis tissues, with future studies focusing on its role in guiding HIPEC treatment. 1. Nat Comm Bio,2022. 2. JCO PO, 2024. Clinical trial information: NCT04847063 .

The use of folic acid as targeting agent in PDT: what about the stability?

SignificanceDespite the conventional treatment combining chemotherapy to a cytoreductive surgery, 60% of women suffered from ovarian cancer will relapse at the end of the treatment. Indeed, our main objective is to develop a targeted PDT treatment of peritoneal carcinomatosis from ovarian cancer to improve the life expectancy of cancer patients. For this, folic acid (FA) was used as a targeting agent, which can be coupled to photosensitizers (PS) to improve the selectivity towards cancer cells that over-expressed FR-α receptors, such as ovarian cancer cells. However, FA can undergo some stability issues. ApproachWe conducted a Design of Experiment (DoE to understand the parameters influencing the degradation of FA. Factors such as light, oxygen, time of storage, temperature and type of medium were evaluated FA-PS conjugates were also tested to determine the influence of PS type on the stability of FA. ResultsFA-PS conjugates demonstrated different photostability, in comparison to FA. . FA-PEG-pyropheophorbide a demonstrates the best photostability. According to the DOE), after more than 80 experimental screenings, temperature, storage time and type of medium were found to be the most influencial parameters on the degradation of FA. FA moleculesalso demonstrated weaker photostability as compared to FA-PEG-pyropheophorbide a, which is an advantage for the efficiency of PDT.

Efficacy of Hyperthermic Pressurized Intraperitoneal Aerosol Chemotherapy in an In Vitro Model Using a Human Gastric Cancer AGS Cell Line and an Abdominal Cavity Model.

Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.

Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study

Background aimsPeritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC. MethodsWe generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells. ResultsIntraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells. ConclusionsTaken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.

A disulfiram/copper gluconate co-loaded bi-layered long-term drug delivery system for intraperitoneal treatment of peritoneal carcinomatosis

To develop a long-term drug delivery system for the treatment of primary and metastatic peritoneal carcinoma (PC) by intraperitoneal (IP) injection, a disulfiram (DSF)/copper gluconate (Cu-Glu)-co-loaded bi-layered poly (lactic acid-coglycolic acid) (PLGA) microspheres (Ms) - thermosensitive hydrogel system (DSF-Ms-Cu-Glu-Gel) was established. Rate and mechanisms of drug release from DSF-Ms-Cu-Glu-Gel were explored. The anti-tumor effects of DSF-Ms-Cu-Glu-Gel by IP injection were evaluated using H22 xenograft tumor model mice. The accumulative release of DSF from Ms on the 10th day was 83.79% without burst release. When Ms were dispersed into B-Gel, burst release at 24 h decreased to 14.63%. The results showed that bis (diethyldithiocarbamate)-copper (Cu(DDC)2) was formed in DSF-Ms-Cu-Glu-Gel and slowly released from B-Gel. In a pharmacodynamic study, the mount of tumor nodes and ascitic fluid decreased in the DSF-Ms-Cu-Glu-Gel group. This was because: (1) DSF-Ms-Cu-Glu-Gel system co-loaded DSF and Cu-Glu, and physically isolated DSF and Cu-Glu before injection to protect DSF; (2) space and water were provided for the formation of Cu(DDC)2; (3) could provide an effective drug concentration in the abdominal cavity for a long time; (4) both DSF and Cu(DDC)2 were effective anti-tumor drugs, and the formation of Cu(DDC)2 occurred in the abdominal cavity, which further enhanced the anti-tumor activity. Thus, the DSF-Ms-Cu-Glu-Gel system can be potentially used for the IP treatment of PC in the future.

Impact of Body Mass Index on Postoperative Pain and Opioid Administration After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique, developed for the treatment of peritoneal carcinomatosis (PC). In this retrospective observational study we assessed the impact of body mass index (BMI) on postoperative pain and opioid consumption. We analyzed pain scores after 100 PIPAC procedures using either oxaliplatin or doxorubicin-cisplatin performed in 49 patients with PC between July 2016 and September 2020. The patients were divided into 3 groups (BMI <18.5, 18.5 ≥ BMI < 25, BMI≥25). Pain was self-rated on a visual analogue scale (VAS) from 0 to 10. Univariate logistic regression analysis identified oxaliplatin and PCI score to be associated with moderate to severe pain (VAS 4-10 at 8 am D1) after adjustment on BMI (OR [95% CI]; 3.26[1.00 - 10.65] p=0.050) and (OR [95% CI]; 1.09[1.01 - 1.17] p=0.019). The level of pain appeared significantly different between the treatment groups (median 2.5[0; 5] vs 0[0; 2.5] p=0.0017) irrespective of BMI (p =0.705 and p=0.118). Multivariate logistic regression analysis identified moderate to severe pain and synchronous PC to be associated with greater use of opioids (OR [95% CI]: 3.91 [1.24 - 12.32]) and (OR [95% CI]: 5.16 [1.71 - 15.58]; respectively. Opioids were administered after 45 procedures (45%) and was comparable between the treatment groups. Opioid administration and length-of-stay were similar among BMI bands. BMI is not related to postoperative pain or opioid use, howevermoderate to severe pain and synchronous PC are factors associated with requiring opioids.

P-115 Cytoreductive surgery and HIPEC in the treatment of peritoneal carcinomatosis: The experience in a tertiary university hospital

P-115 Cytoreductive surgery and HIPEC in the treatment of peritoneal carcinomatosis: The experience in a tertiary university hospital

Localized chemotherapy approaches and advanced drug delivery strategies: a step forward in the treatment of peritoneal carcinomatosis from ovarian cancer.

Peritoneal carcinomatosis (PC) is a common outcome of epithelial ovarian carcinoma and is the leading cause of death for these patients. Tumor location, extent, peculiarities of the microenvironment, and the development of drug resistance are the main challenges that need to be addressed to improve therapeutic outcome. The development of new procedures such as HIPEC (Hyperthermic Intraperitoneal Chemotherapy) and PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) have enabled locoregional delivery of chemotherapeutics, while the increasingly efficient design and development of advanced drug delivery micro and nanosystems are helping to promote tumor targeting and penetration and to reduce the side effects associated with systemic chemotherapy administration. The possibility of combining drug-loaded carriers with delivery via HIPEC and PIPAC represents a powerful tool to improve treatment efficacy, and this possibility has recently begun to be explored. This review will discuss the latest advances in the treatment of PC derived from ovarian cancer, with a focus on the potential of PIPAC and nanoparticles in terms of their application to develop new therapeutic strategies and future prospects.

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

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). Single-center retrospective cohort study included consecutive patients having PIPAC for PM of different primary between January 2015 and January 2020. 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 30.9months in the per protocol group and 12.9months in patients having <3 PIPACs (=0.519). 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.

Immunotherapy for Peritoneal Carcinomatosis: Challenges and Prospective Outcomes

Peritoneal metastasis, also known as peritoneal carcinomatosis (PC), is a refractory cancer that is typically resistant to conventional therapies. The typical treatment for PC is a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Recently, research in this area has seen significant advances, particularly in immunotherapy as an alternative therapy for PC, which is very encouraging. Catumaxomab is a trifunctional antibody intraperitoneal (IP) immunotherapy authorized in Europe that can be used to diminish malignant ascites by targeting EpCAM. Intraperitoneal (IP) immunotherapy breaks immunological tolerance to treat peritoneal illness. Increasing T-cell responses and vaccination against tumor-associated antigens are two methods of treatment. CAR-T cells, vaccine-based therapeutics, dendritic cells (DCs) in combination with pro-inflammatory cytokines and NKs, adoptive cell transfer, and immune checkpoint inhibitors are promising treatments for PC. Carcinoembryonic antigen-expressing tumors are suppressed by IP administration of CAR-T cells. This reaction was strengthened by anti-PD-L1 or anti-Gr1. When paired with CD137 co-stimulatory signaling, CAR-T cells for folate receptor cancers made it easier for T-cell tumors to find their way to and stay alive in the body.

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis

Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and 177Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of 177Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. 177Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.

Perspectives of pressurized intraperitoneal aerosol chemotherapy in terms of primary ovarian cancer with peritoneal carcinomatosis treatment

The relevance of the problem of increasing the effectiveness of standard treatment of ovarian cancer is determined by the following characteristics of the disease: high one‑year mortality, high recurrence rate and unsatisfactory results of their treatment. Peritoneal carcinomatosis in ovarian cancer occurs in 65–70 % of cases. The standard modern approach to the treatment of ovarian cancer is a combination of surgical treatment and systemic intravenous chemotherapy. At the same time, more than 70 % of ovarian cancer cases are first diagnosed at stages III–IV. However, despite the successes in the field of surgery and drug treatment, the five‑year survival rate is no more than 24 % at the III and 4.6 % at the IV stage of the disease. One of the frontiers of ovarian cancer resistance to therapy is peritoneal carcinomatosis. Its resistance to therapy is due to the low bioavailability of cytostatics in metastases on the peritoneum to almost zero. In order to increase bioavailability, various forms of intra‑abdominal chemotherapy are used. The technique of pressurized intraperitoneal aerosol chemotherapy (PIPAC) has a number of advantages over other methods of intra‑abdominal antitumor treatment. These advantages include the uniform distribution of cytostatics over the peritoneum, the absence of penetration of cytostatics beyond the peritoneum, which allows PIPAC to be combined with systemic chemotherapy, low trauma and good tolerability of the procedure. PIPAC was implemented into clinical practice in 2011, and since then has been widely used in a number of foreign and domestic clinics. The conducted studies confirm the safety of the technique and its effectiveness against peritoneal carcinomatosis. The data of multicenter studies and the analysis of available literature data, as well as the successful own experience of PIPAC use create prerequisites for investigating the effectiveness of intra‑abdominal aerosol chemotherapy under pressure in relation to peritoneal carcinomatosis in ovarian cancer.

Development of a light emitting device for the treatment of peritoneal carcinomatosis of ovarian origin by intracavitary photodynamic therapy

Development of a light emitting device for the treatment of peritoneal carcinomatosis of ovarian origin by intracavitary photodynamic therapy

Hyperthermic intraperitoneal chemotherapy for management of gastrointestinal and biliary tract malignancies: a systematic review and meta-analysis of randomized trials.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) promised to transform the management of peritoneal carcinomatosis (PC). Forty years since the introduction of the technique, published data from randomized controlled trials (RCTs) remain scarce. We assessed the cumulative comprehensive available evidence on the use of HIPEC in gastrointestinal (GI) and biliary tract malignancies and established the current benchmark for GI HIPEC research in both the prevention and treatment of peritoneal metastases. RCTs were identified through a systematic search of Medline, Cochrane and Embase databases. Overall survival and progression-free survival were the outcomes of interest. The search resulted in 13 RCTs for gastric cancer (10 on prophylactic and 3 on therapeutic HIPEC), 4 for colorectal cancer (2 on prophylactic and 2 on therapeutic HIPEC), and 1 for pancreatic cancer. No RCTs were identified that included other types of GI or biliary tract cancers. Current randomized evidence does not support any overall survival benefit from the use of HIPEC in the adjuvant setting for gastric cancer or for colorectal cancer in any setting. Despite the survival benefit noticed in the treatment of PC from gastric cancer (risk ratio 0.85, 95% confidence interval 0.77-0.93; P<0.001), the results were derived from only 190 patients. The current evidence from RCTs does not support the use of HIPEC in the treatment/prevention of PC in GI and biliary tract malignancies. HIPEC should continue to be considered experimental until level 1 evidence from properly designed international multicenter studies becomes available.

PIPAC nebulizer: How to test the new devices in the market, expert recommendations.

Pressurized intraperitoneal aerosol chemotherapy, named PIPAC, is now used in many centers around the world and as an intraperitoneal drug delivery system for treatment of peritoneal carcinomatosis. Recently, many of us have encountered problems during PIPAC procedures due to changes in material and production features of the original PIPAC nebulizer. Concomitantly, new PIPAC nebulizers proposed by other manufacturers are being launched on the market; which claim that they are the same as the original device in delivering PIPAC. However, these new devices are all different in terms of materials, technical characteristics and costs. We have considered that, to maintain the acquired results of PIPAC, we must ensure that the new systems are equivalent. The characteristics deemed essential by the expert group are as follows: 1: The nebulizer must be able to create droplets through an injector pressure between 10 and 20 bars, 2: The mean droplet size must be 3 micrometers, with 95% of the droplets between 0 and 10 micrometers, 3: The diffusion angle must be 70 degrees, which is the minimum.