Refractory Malignant Ascites Research Articles

Injectable thermosensitive hydrogels loaded with irradiated tumor cell-derived microparticles and manganese activate anti-tumor immunity

Immunosuppressive tumor microenvironment and inadequate activation of the innate immune system are important reasons for the failure of systemic anti-tumor immunotherapy. Irradiated tumor cell-derived microparticles (RMPs) can induce immunogenic cell death (ICD) of tumor cells and inhibit the M2-like phenotype of tumor-associated macrophages (TAMs). The current study found that double-stranded DNA was enriched in RMPs, which combined with manganese ions (Mn2+), the natural activator of cGAS-STING signaling, and synergistically amplified cGAS-STING signaling cascade in antigen-presenting cells (APCs). On this basis, a polyamino acid thermosensitive hydrogel delivery system was designed to simultaneously load RMPs and Mn2+. The obtained RMPs@Mn2+ hydrogel exhibited thermosensitivity, biocompatibility and sustained release characteristics. The intratumoral injection of RMPs@Mn2+ slowly released RMPs and Mn2+, inducing ICD of tumor cells, continuously activating cGAS-STING signaling of APCs, reprograming TAMs to M1-like phenotype, and promoting the activation of dendritic cells in tumor draining lymph nodes. The full activation of innate immunity at the tumor site further promoted priming and tumor infiltration of T cells, leading to tumor regression. RMPs@Mn2+ combined with anti-PD-1 achieved strong anti-cancer efficacy in a refractory malignant ascites model, in which more than 50 % of mice with malignant ascites achieved complete regression and long-term immune memory.

Effective palliation of refractory ascites in cirrhosis is challenging.

Palliative care is often suboptimal for patients with end-stage liver disease (ESLD). Ascites remains the most common complication in ESLD. Though long-term abdominal drains (LTAD) are commonly used in refractory malignant ascites, the standard care for ESLD is hospital drainage (large volume paracentesis (LVP)). There is an ongoing National Institute for Health and Care Research (NIHR) funded trial (REDUCe 2 Study) (ISRCTN269936824) comparing palliative LTAD to LVP in ESLD. This 35-site trial is being conducted in England, Scotland and Wales. To understand the views and experience of healthcare professionals (HCP) on the use of palliative LTAD in ESLD. An electronic survey comprised of seven questions with fixed quantitative options and three exploratory questions was used between August-December 2019. The survey was distributed electronically via the British Association for Study of Liver newsletter and to relevant hospital departments in Southeast England and Northeast London. An email reminder was sent at 4 and 8 weeks after the initial invitation to the survey. There were 211 respondents (hepatologists (36.5%), specialist nurses (24.6%), gastroenterologists (16.6%), trainees (17%) and others (5.2%)). All respondents had access to LVP, 86% to a transjugular intrahepatic portosystemic shunt procedure for patients, 67% to LTADs and 10% to other options, such as the automated low-flow ascites (ALFA) pump. The majority of respondents to the survey (68%) reported their experience of using LTAD. Almost all respondents (91%) were willing to consider LTAD in ESLD. However, the main deterrents of this were the perceived risk of infection (90%), followed by LTAD management in community (57%). Some 51% of those with prior experience of using LTAD reported clinical complications for patients (including bleeding, infection and renal impairment), 41% reported technical issues and 35% inadequate community support. Almost all HCPs are willing to consider palliative LTAD in refractory ascites due to ESLD, but the main deterrents are the perceived infection risk and lack of published data to guide community management. The REDUCe 2 trial will clarify if these concerns are real and provide conclusive evidence on role, if any, of palliative LTADs in this vulnerable and under researched cohort with ESLD.

Efficacy of Pigtails for the Management of Refractory Malignant Ascites or Effusion: A Systematic Retrospective Chart Review of an Institution

Introduction: Malignant ascites and effusions have been observed in various diseases and persistent ascites or effusion from any of causes prompts the need for urgent first-line therapies. Refractory forms of ascites and effusion can cause noteworthy symptoms and can severely affect the quality of life (QoL). We therefore assessed the viability, efficacy, and patient-reported results of pigtails in the administration of refractory ascites or effusion due to malignancy.
 Aims & Objectives: We aimed to assess the viability, efficacy and patient-reported results of pigtails in the administration of refractory ascites or effusion by malignancy.
 Place and duration of study: It was conducted in Vascular Interventional Radiology Department, Dow Institute of Radiology, Dow University of Health Sciences, Ojha Campus for a period of 18 months between January 2021 and June 2022.
 Material & Methods: A retrospective chart review from a single center was done. All available data of the Interventional Radiology Department was utilized to identify patients(n=65) with refractory malignant ascites or effusion who underwent pigtail placement. Data analysis was performed using SPSS version 21, p?0.05 was taken as significant. Results: Procedural success rate was 100% for placement and similarly no mortality was observed. Duodenal, liver and ovarian cancer was the primary source of malignancy. The catheters, 8Fr (n=45, 69.20%) and10Fr (n=20, 30.80%) were implanted. Leakage was the highest experienced complication followed by dislodgement. Overall catheter mean survival time was [23.37days, 95%:21.63- 25.10]. The estimated mean [(24.46, 95%21.98-26.94 Vs 22.53, 95%20.08-24.97)]
 duration of catheter dwelling time for pleural effusion was greater than that of ascites (p>0.05). Overall, estimated mean time for 8Fr catheter was greater than that of 10 Fr (p=0.048). Infection and leakage had an estimated mean catheter survival time lower than that of dislodgment and occlusion [log rank-chi square 13.64,p=0.003].
 Conclusion: Procedural success rate achieved was 100% and acceptable outcomes in terms of complications and catheter time. These minimally invasive treatment options should be utilized to soothe symptoms and improve the QoL.Furthermore, experimental studies with bigger sample size assessing the adverse outcome and ascertaining the possible cost savings should be performed.

Adverse effects of cell-free and concentrated ascites reinfusion therapy for malignant ascites: a single-institute experience

BackgroundCell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including hypoalbuminemia. CART has recently been applied in the treatment of cancer patients. This study was performed to assess the safety of CART in a single cancer institute.MethodsWe retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute.ResultsThe median weight of ascites before and after concentration was 4,720 g and 490 g (median concentration rate, 10.0-fold), The median amounts of total protein and albumin were 64.0 g and 32.6 g (median recovery rates, 44.9% and 49.0%), respectively. Thirty-three adverse events (AEs) were observed in 22 (9.4%) of 233 procedures; 30 of these events occurred after reinfusion. The most common reinfusion-related AEs were fever (13 events) and chills (10 events). Univariate analyses revealed no significant relationships between the frequency of AEs and age, sex, appearance of ascites, weight of harvested and concentrated ascites, the ascites processing rate (filtration and concentration), weight of saline used for membrane cleaning, amount of calculated total protein for infusion, or prophylaxis against AEs; the reinfusion rate of ≥ 125 mL/h or ≥ 10.9 g/h of total protein affected the frequency of AEs, regardless of the prophylactic use of steroids.ConclusionsThe observed AEs were mainly mild reactions after reinfusion, which were related to a reinfusion rate of volume ≥ 125 mL/h, a simple indicator in practice, or total protein ≥ 10.9 g/h. Although our study was retrospective in nature and undertaken in a single institute, this information may be helpful for the management of cancer patients with refractory malignant ascites using CART.

Feasibility of a fast-track randomized controlled trial of cell-free and concentrated ascites reinfusion therapy for patients with refractory malignant ascites

BackgroundMalignant ascites often causes discomfort in advanced cancer patients. Paracentesis is the most common treatment modality, but it requires frequently repeated treatment. Cell-free and concentrated ascites reinfusion therapy (CART) may prolong the paracentesis interval, but controlled trials are lacking. We assessed the feasibility of a randomized controlled trial of CART vs. paracentesis alone for patients with refractory malignant ascites.MethodsThis study was an open-label, fast-track, randomized controlled, feasibility trial. Patients admitted to four designated cancer hospitals who received no further anticancer treatments were eligible. Patients were randomly assigned 1:1 to a CART arm or control (simple paracentesis) arm. The feasibility endpoint was the percentage of patients who completed the study intervention. Secondary endpoints included paracentesis-free survival, patient’s request on the questionnaire for paracentesis (PRO-paracentesis)-free survival (the period until the patients first reported that they would want paracentesis if indicated), and adverse events.ResultsWe screened 953 patients for eligibility. Of 61 patients with refractory malignant ascites, 21 patients were determined as eligible. Finally, 20 patients consented and were allocated; 18 patients (90%, 95% CI: 68.3–98.8) completed the study intervention. All patients had an ECOG performance status of 3 or 4. The median drained ascites volume was 3,200 mL in the CART arm and 2,500 mL in the control arm. In the CART arm, the median reinfused albumin volume was 12.6 g. Median paracentesis-free survivals were 5 days (95% CI: 2–6) in the CART arm, and 6 days (3–9) in the control arm. Median PRO-paracentesis-free survivals were 4 days (2–5) and 5 days (1–9), respectively. A total of 73% of patients received paracentesis within 2 days from their first request for the next paracentesis. One patient in the CART arm developed Grade 1 fever.ConclusionsA fast-track randomized controlled trial of CART for patients with malignant ascites is feasible. The efficacy and safety of CART should be assessed in future trials. PRO-paracentesis-free survival may be a complementary outcome measure with paracentesis-free survival in future trials.Trial registrationRegistered at University Hospital Medical Information Network Clinical Trial Registry as UMIN000031029. Registered on 28/01/2018.

Strategies of chemotherapy for peritoneal metastasis of gastrointestinal cancer

Peritoneal metastasis of gastrointestinal cancer is an independent factor that seriously affects the prognosis of patients. The "seed-soil" theory is considered to be the main theory to explain peritoneal metastasis. Because of the small size of peritoneal metastatic nodules at the initial stage, early diagnosis is particularly difficult, therefore, the risk assessment of peritoneal metastasis is very important. Recently, the diagnosis methods have gradually developed from clinicopathological factors to cytology and molecular level. In addition, the integrated assessment of multiple groups including radiomics further enriches the accurate diagnosis of peritoneal metastasis. Peritoneal metastasis is a big challenge in the treatment of gastrointestinal cancer which may also lead to refractory malignant ascites, intestinal obstruction, cachexia and other related complications. At present, the treatment is based on systemic chemotherapy. The combination of surgery, intraperitoneal chemotherapy and HIPEC is an effective treatment for peritoneal metastasis of gastrointestinal cancer. How to enrich peritoneal metastasis patients with potential benefits, how to determine the timing of conversion surgery, how to further optimize the existing treatment plan, especially how to formulate treatment plan for patients after conversion surgery, call for improved study design and prospective randomized controlled trials. The goal of continuous efforts is to effectively prolong the survival of gastrointestinal cancer trials patients with peritoneal metastasis.

Patterns and infection outcomes of bacterial colonization in patients with indwelling abdominal drains for malignant ascites.

Indwelling abdominal drains for intermittent drainage is an effective treatment for refractory malignant ascites, bacterial colonization and subsequent drain-related infection is however a common concern. This study aimed to investigate the patterns of bacterial colonization and the subsequent infection outcomes in patients with indwelling abdominal drains. All consecutive advanced cancer patients with newly inserted indwelling abdominal drains and who were under the service of the ascites clinic of our institution for intermittent drainage between January 2011 and March 2018 were screened for study eligibility. Patients with positive surveillance ascitic fluid culture without immediate drain-related infection were included in the final analysis. Clinical information during the drainage period was prospectively collected using standardized clinical assessment forms. These assessment forms and other medical records were retrospectively reviewed. Sixty nine patients developed bacterial colonization without immediate infection during the study period. The most common cancer diagnosis was hepatocellular carcinoma (HCC), which comprise 30.4% of the population. Central venous catheters (CVCs) were inserted in 76.8% of patients and pigtail drains in 23.2% as the indwelling abdominal drain. The median duration from drain insertion to the development of bacterial colonization was 18.0 days. Staphylococci, Diphtheroid bacilliand Enterococci were the most common types of bacteria isolated during colonization. Thirty patients (43.5%) developed drain-related infection subsequently and the median time from bacterial colonization to development of infection was 14.5 days. The incidence rate of drain-related infection after bacterial colonization was 1.78 per 100-catheter days and the 1-month infection-free survival was 54.4%. Five patients (7.2%) developed peritonitis and 4 of them died from the infection episode. Decrease in body mass index (BMI) (P=0.03), having 3 or more episodes of drainage in the ascites clinic before bacterial colonization (P=0.03), presence of Escherichia coli (P=0.04) and Bacillus species (P=0.04) in surveillance ascitic fluid culture were significantly correlating with infection outcomes in univariate analyses. HCC as cancer diagnosis (OR 8.85, 95% CI: 1.86-42.07, P=0.006) and decrease in body weight (OR 1.20, 95% CI: 1.02-1.42, P=0.03) were significant factors that correlated with infection outcomes in multivariate analysis. Bacterial colonization and subsequent progression into drain-related infection are common in patients on indwelling abdominal drains for malignant ascites. Staphylococci is the most common type of bacteria causing both colonization and subsequent drain-related infection. HCC and decrease in body weight are significant factors that correlate with infection outcomes after bacterial colonization.

Abstract A66: Intracavity infusions of autologous cellular immunotherapy in the treatment of refractory malignant pleural and ascites: A Chinese population-based cohort study

Abstract Objectives: we have explored the potential efficacy and safety of autologous adoptive T cells represented by dendritic cell (DC)-cytokine-induced killer (CIK) infused within cavity in advanced cancer patients with malignant pleural effusion and ascites. Methods: The apheresis for collection of peripheral blood mononuclear cells was performed in 37 recruited patients. DC-CIKs were expanded ex vivo until qualified for intracavity perfusions for three consecutive times. The quantitative volume of malignant effusions was recorded by radiologic imaging assay. The clinical adverse reactions were analyzed. Results: For the quantitative assay for those effusions, 1 patient has achieved complete response, 13 patients have achieved PR, 12 patients have stable diseases, and 11 patients have progressive diseases, respectively, yielding a total clinical control rate of 70.3%. After adjusting for competing risk factors, number of concurrent metastasis distribution of organs (p=0.007) and infused number of CIKs (p=0.013) remained independent factors associated with malignant effusion remission. Further exploration demonstrated that the infused CD3+/CD8+ and CD8+/CD28- T-cell populations were able to determine the clinical responses (P<0.05). Moreover, elevated peripheral blood CD3+/CD8+ and declined CD4+/CD25+ T-cell population were noticed in malignant effusion remission group compared with non-remission group (P <0.05). Fewer adverse reactions were recorded. Conclusions: We have provided the novel therapeutic approach by autologous cellular immunotherapy with confirmed clinical efficacy and safety in the stably controllable malignant effusions. The intracavity infusions were featured by the immunologic T-cell recovery and clinical remission of those effusions. Note:This abstract was not presented at the conference. Citation Format: Guoliang Qiao. Intracavity infusions of autologous cellular immunotherapy in the treatment of refractory malignant pleural and ascites: A Chinese population-based cohort study [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A66.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma: patient selection and special considerations.

Malignant peritoneal mesothelioma (MPM) is a rare, aggressive malignancy that typically presents with vague symptoms, ascites, and/or diffuse peritoneal studding. Despite findings of advanced disease within the peritoneal cavity, spread beyond the abdomen is uncommon. Although advances in systemic chemotherapy have been made, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remain the mainstay of treatment. Median overall survival of approximately 50 months with CRS/HIPEC has been demonstrated, with age, gender, histologic subtype, peritoneal carcinomatosis index, comorbidities, nodal and extra-abdominal metastases, and completeness of cytoreduction all playing a role in prognosis. In patients with refractory malignant ascites and unresectable disease, complete resolution of ascites and improvement in quality of life have been demonstrated with palliative HIPEC. In appropriately selected patients, CRS/HIPEC plays a critical role in the treatment and palliation of MPM.

Safety and Effectiveness of Palliative Tunneled Peritoneal Drainage Catheters in the Management of Refractory Malignant and Non-malignant Ascites.

To determine the safety and effectiveness of tunneled peritoneal catheters in the management of refractory malignant and non-malignant ascites. An IRB-approved retrospective review was undertaken of patients who underwent ultrasound and fluoroscopy-guided tunneled peritoneal catheter placement for management of refractory malignant or non-malignant ascites between January 1, 2009, and March 14, 2014. A total of 137 patients (76M/61F, mean age 62.9years) underwent tunneled peritoneal catheter placement for refractory malignant (N=119; 86.9%) or non-malignant (N=18; 13.1%) ascites. Technical success was 100% with no immediate complications. Nineteen patients (13.9%) experienced a total of 11 minor and 12 major complications. Nine patients developed a catheter-associated infection. The remaining complications included leakage at the dermatotomy site (N=8), catheter dislodgement (N=2), obstruction (N=2), and groin pain (N=2). Patients who developed a catheter-associated infection had a significantly longer catheter dwell time compared to those who did not develop an infection (median, 96.5 vs. 20days; p<0.01). Nine patients (6.6%) were lost to follow-up. Of the remaining 128 patients, 125 died and the majority had a catheter in place (90.4%) at the time of death. There was one catheter-associated death (bacterial peritonitis; 0.8%). The median time from catheter placement to death was significantly shorter in patients with malignant versus non-malignant ascites (18.5 vs. 85days; p<0.0001). Tunneled peritoneal drainage catheters are effective and relatively safe in the management of malignant and non-malignant ascites. Longer catheter dwell time may be a risk factor for catheter-associated infection, particularly in patients with a longer anticipated survival in the palliative setting.

Efficacy and safety of reinfusion of concentrated ascitic fluid for malignant ascites: a concept-proof study.

Malignant ascites is one of the symptoms causing discomfort in advanced cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is one treatment modality, but controlled trials are limited. The primary aim of this study was to explore the efficacy and safety of CART, as well as their predictors, to obtain data for planning a further controlled trial. This was a single center retrospective cohort study in patients with refractory malignant ascites. Consecutive adult patients who underwent CART were enrolled. The primary endpoints were the time to next paracentesis and seven patient-reported symptoms (e.g., abdominal pain and distension). The secondary endpoints were adverse events, laboratory findings, and physical findings. A total of 104 CART procedures for 51 patients were analyzed. The median time to next paracentesis was 27days (95% CI, 21-35). Intensities of all seven symptoms were significantly improved after CART (p < 0.0001 for all symptoms). Grade 3 hypotension occurred during one procedure, and mild fever occurred in 5%. Total protein, albumin, and estimated glomerular filtration rate were significantly increased. Hemorrhagic ascites, ascites white blood cell count, serum total protein, and lymphocyte percentages were the independent predictors of the time to next paracentesis. The effects of reinfusion of concentrated ascitic fluid may be maintained for 1month, being potentially longer than that of total paracentesis alone. This study had no comparison groups and examined the short-term effect. A randomized controlled study to compare the long-term effects of total paracentesis alone vs. CART is necessary.

Peritoneal Dialysis Catheters to Treat Refractory Non-Malignant Ascites.

Refractory non-malignant ascites is associated with significant morbidity. Serial, large-volume paracentesis is a common treatment. Tunneled peritoneal dialysis (PD) catheters are an effective treatment for refractory malignant ascites, but there are limited data on complications and effectiveness for non-malignant ascites. We reviewed all 13 PD catheter insertions between 2010 - 2015 for this indication at our center. The median catheter survival time was 146 days. No complications occurred during catheter insertion, and no mechanical complications occurred after catheter insertion. One case of peritonitis developed over 217 catheter months. Peritoneal dialysis catheters may be a safe and effective option to manage refractory non-malignant ascites. Prospective, randomized trials are needed to better evaluate potential risks and benefits.

Terapia intraperitoneal paliativa en ascitis maligna refractaria

Conventional treatment of refractory malignant ascites is an oncological challenge since it provides little lasting symptomatic improvement. Intraperitoneal therapy, evaluated mainly through series and case reports, and some clinical trials include the use of radioisotopes, chemotherapy, with and without hyperthermia, immunological and biological therapy and others. It has been studied mainly in ascites from ovarian and gastrointestinal cancer. With variable response rates, and although direct comparison is not possible, the most successfully treatments are hyperthermic intraperitoneal chemotherapy (overall response rate between 85.7% and 100%), and catumaxomab, which compared to paracentesis, demonstrated a puncture-free survival of 46 vs. 11 days (HR 0.254) and a median time to next paracentesis of 77 vs. 13 days (HR 0.169). This had a positive impact on quality of life, which is the main goal in the palliative setting. Research in this field continues looking for more lasting, safe, and cost-effective results.

Abstract No. 510 - Safety and effectiveness of palliative tunneled peritoneal drainage catheters in the management of refractory malignant and non-malignant ascites

Abstract No. 510 - Safety and effectiveness of palliative tunneled peritoneal drainage catheters in the management of refractory malignant and non-malignant ascites

Tenckhoff tunneled peritoneal catheter placement in the palliative treatment of malignant ascites: technical results and overall clinical outcome.

BackgroundTo assess the technical and clinical outcome of percutaneous insertion of tunneled peritoneal catheters in the palliative treatment of refractory malignant ascites and to determine the safety and feasibility of intraperitoneal administration of cytotoxic drugs through the tunneled catheter.Materials and methodsConsecutive patients palliatively treated with a tunneled peritoneal catheter to drain the malignant ascites were identified. Patients’ medical history, procedural and clinical follow-up data, including complications and estimated survival, were reviewed. Additionally, a sub analysis of the patients with widespread ovarian cancer and refractory ascites treated with or without intraperitoneal administration of cytotoxic drugs was made.ResultsIn all 94 patients it was technically feasible to insert the peritoneal drainage catheter and to drain a median of 3260 cc (range 100 cc – 8500 cc) of malignant ascitic fluid. Post procedural complications included catheter infection (n = 2; 2%), fluid leakage around the entry site (n = 4; 4%), catheter occlusion (n = 2; 2%), sleeve formation around the catheter tip (n = 1; 1%) and accidental loss of the catheter (n = 1; 1%). There was no increase in catheter infection rate in patients treated with or without intraperitoneal administration of cytotoxic drugs. Median overall survival after catheter insertion is 1.7 months.ConclusionsPercutaneous insertion of a tunneled Tenckhoff catheter for the palliative drainage of malignant ascites and intraperitoneal infusion of cytotoxic drugs is feasible and associated with a very low complication rate, including catheter infection. These tunneled peritoneal lines are beneficial for symptomatic palliative treatment of refractory ascites and allow safe intraperitoneal chemotherapy.

The Ca125 Concentration in Intraperitoneal Fluid as A Prognostic Factor in Ovarian Cancer Patients with Refractory Malignant Ascites

Aim: Chemotherapy refractory malignant ascites in ovarian cancer patients is still a serious problem which leads to significant deterioration in the quality of life by causing distressing symptoms such as pain, nausea, vomiting, anorexia, dyspnea. In this group of patients overall survival is short. Efficacy and tolerability of current available treatments is limited. The serum Ca125 concentration has been well documented as an useful marker for evaluating intravenous chemotherapy response in epithelial ovarian cancer patients. The main goal of this study was estimation of Ca125 concentration decline rate in the intraperitoneal fluid as a prognostic factor for intraperitoneal chemotherapy response and patients survival. Material and method: Patients included to this analysis attained intravenous chemorefractory malignant ascites in the ovarian cancer course. An intraperitoneal chemotherapy was cisplatin based. Ca125 concentration was measured twice in intraperitoneal fluid: before intraperitoneal chemotherapy infusion and 24 hours after. Results: Patients with Ca125 intraperitoneal concentration decrease more than 3 times lived longer than patients with lower Ca126 concentration reduction (78,5 vs 33,1 months), p=0.06. The results of this study have many limitations, mostly due to the group of pts being small. That is why the results should be taken into consideration with caution. Conclusions: Intraperitoneal fluid Ca125 concentration decrease rate after intraperitoneal chemotherapy seems to be prognostic factor for overall survival in ovarian cancer patients with refractory malignant ascites.

453. Office-based Denver peritoneovenous shunt for malignant ascites: A feasibility study

Background: Management of refractory malignant ascites is part of palliative care to improve the patient’s quality of life. In patients with malignant ascites, peritoneovenous shunts can control ascites, but the potential risks of the procedure need to be weighed against the requirement of hospital stay and operatory room utilization. We report our experience in peritoneovenous shunt placement as an outpatient procedure.

Intraperitoneal Bevacizumab (Bev) for Control of Malignant Ascites Due to Advanced-Stage Gastrointestinal Cancers (Gi): a Multicenter Double-Blind, Placebo (Pl)-Controlled, Randomized Phase Ii Study. Aio Sup-0108

ABSTRACT Aim: Malignant Ascites is debilitating for pts. with advanced cancer which negatively impacts the quality of life (QoL). Causative treatment approaches are still limited. It has previously been shown that tumor cell production and/or increases of Vascular Endothelial Growth Factor (VEGF) might be a major cause of the formation of malignant ascites. Intraperitoneal Bev could therefore be an option for symptom control of refractory malignant ascites. Methods: Pts. with advanced GI cancer and malignant ascites who had received paracentesis at least once within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal Bev (400mg absolute in 100 ml NaCl 0.9%) or Pl after paracentesis. During the 8-week treatment period, a minimum interval of 14d was kept between the applications of the study drug. First primary endpoint was the paracentesis-free survival (ParFS). Second primary endpoint was best response (BR) defined as the longest paracentesis-free period within the 12-week observation period. Further endpoints were overall survival, QoL, serum and ascites VEGF. ParFS and BR were compared using the logrank test and the Wilcoxon-Mann-Whitney test, respectively. Results: 53 Patients (median age 63y) were randomized (37 Bev/16 Pl arm) whereas 49 pts. received at least one application of the study drug and qualified for the intention to treat analysis. The median ParFS was 14d (CI:11-17d) in the Bev arm and 10.5d (CI: 7-21d) in the Pl arm (hazard ratio 0.74, CI:0.40-1.37; p = 0.16). The BR was 19d for the Bev arm (range 6-66d) and 17.5d for the Pl arm (range 4-42d) with a p value of 0.85. Median OS was 64d (CI: 45-103d) for the Bev arm and only 31.5d (CI: 20-117d) for the Pl arm (p = 0.31). The proportion of pts. with at least one CTC grade 3-5 event occurred was similar with 20/33 (61%) in the Bev arm and 11/16 (69%) in the Pl arm. Results on serum and ascites VEGF will be presented at the meeting. Conclusions: In this unfavorable group of terminally ill pts. intraperitoneal Bev was well tolerated but did not result in a significantly better symptom control of malignant ascites compared to the control. Disclosure: D. Atanackovic: Research Support Roche; D. Arnold: Honoraria & Research Support: Roche; J. Russel: Advisory Board Roche. All other authors have declared no conflicts of interest.

Safety and efficacy of the PleurX catheter for the treatment of malignant ascites.

Malignant ascites is a common complication seen in association with various types of neoplastic processes. Due to high recurrence rates, patients may require multiple paracenteses, which have associated complications such as increased risk of bleeding, infection, pain, and volume and electrolyte depletion. This study evaluated the management of malignant ascites by placement of the PleurX® tunneled catheter system at a single center. This was a retrospective study of 38 patients who underwent PleurX catheter placement for refractory malignant ascites between February 2006 and March 2012 at our institution. Pretreatment characteristics and outcome measures were reported using descriptive statistics. The population included 21 males and 17 females with a mean age of 60.6 years (range, 36-79 years) diagnosed with metastatic disease from a variety of primary malignancies, the most common of which was pancreatic cancer (10 patients). In 84% of patients (32/38) who were not lost to follow-up, mean survival time was 40.7 days (range 4-434 days). Technical success rate of catheter placement was 100%. The PleurX catheter can be used to manage malignant ascites in severely ill patients with metastatic cancer, with a high rate of procedural success and a low incidence of potentially serious adverse events, infections, or catheter-related complications.

Bevacizumab administered intraperitoneally as palliative treatment of malignant refractory ascites.

e20617 Background: Intra-peritoneal administration of Bevacizumab (IP-Beva) in refractory malignant ascites seems to be well tolerated and efficient in small clinical series. We aim to evaluate the...