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Cancers Feb 2023Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients... (Review)
Review
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 (I 28.41%, = 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.
PubMed: 36831468
DOI: 10.3390/cancers15041125 -
Cancer Metastasis Reviews Mar 2023Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Genetic Profile; Proto-Oncogene Proteins p21(ras)
PubMed: 36723696
DOI: 10.1007/s10555-023-10088-0 -
Clinics (Sao Paulo, Brazil) 2022The objective of this systematic review is to provide efficacy and safety data in the application of Intra-Abdominal Hyperthermia Chemotherapy (HIPEC) and Cytoreductive... (Review)
Review
Efficacy and safety in the use of intraperitoneal hyperthermia chemotherapy and peritoneal cytoreductive surgery for pseudomyxoma peritonei from appendiceal neoplasm: A systematic review.
The objective of this systematic review is to provide efficacy and safety data in the application of Intra-Abdominal Hyperthermia Chemotherapy (HIPEC) and Cytoreductive Surgery (CRS) in patients with Peritoneal Pseudomyxoma (PMP) of origin in the cecal appendix. The databases Medline and Central Cochrane were consulted. Patients with PMP of origin in the cecal appendix, classified as low grade, high or indeterminate, submitted to HIPEC and CRS. The results were meta-analyzed using the Comprehensive Metanalysis software. Twenty-six studies were selected to support this review. For low-grade PMP outcome, 60-month risk of mortality, Disease-Free Survival (DFS), and adverse events was 28.8% (95% CI 25.9 to 32), 43% (95% CI 36.4 and 49.8), and 46.7% (95% CI 40.7 to 52.8); for high-grade PMP, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 55.9% (95% CI 51.9 to 59.6), 20.1% (95% CI 15.5 to 25.7) and 30% (95% CI 25.2 to 35.3); PMP indeterminate degree, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 32.6% (95% CI 30.5 to 34.7), 61.8% (95% CI 58.8 to 64.7) and 32.9% (95% CI 30.5 to 35.4). The authors conclude that the HIPEC technique and cytoreductive surgery can be applied to selected cases of patients with PMP of peritoneal origin with satisfactory results.
Topics: Appendiceal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Hyperthermic Intraperitoneal Chemotherapy; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Retrospective Studies
PubMed: 35576869
DOI: 10.1016/j.clinsp.2022.100039 -
The Journal of Surgical Research Jul 2013Pseudomyxoma peritonei (PMP) is an uncommon but lethal variant of adenocarcinoma. Many recent case series have reported improved survival with the combination of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pseudomyxoma peritonei (PMP) is an uncommon but lethal variant of adenocarcinoma. Many recent case series have reported improved survival with the combination of cytoreductive surgery and intraperitoneal chemotherapy (IPEC) in treating PMP. The aim of this study was to analyze the published studies for improved survival with this treatment strategy.
METHODS
Data from all studies using IPEC in treating PMP were analyzed. We searched PubMed, MEDLINE, and the Cochrane Library (through September 2011). Studies were limited to English and PMP with appendiceal origin. Twenty-nine studies were identified, with 15 studies from different treatment centers that were specifically analyzed for differences in 5-y mortality and morbidity. Observed to expected (OE) ratios were calculated for both mortality and morbidity.
RESULTS
Mean and median 3-y, 5-y, and 10-y survival rates were 77.18%/77.85%, 76.63%/79.5%, and 57.3%/55.9%, respectively. Of the 10 studies that had sufficient data to calculate OE ratios from the 5-year mortality data, two had OE ratios lower than 1. Of the 11 studies that had data sufficient to calculate OE ratios from the morbidity data, four had OE ratios that were less than 1.
CONCLUSIONS
Combining cytoreductive surgery and IPEC improves the survival of patients with PMP, regardless of treatment modality. Although this treatment strategy is associated with an increased risk of morbidity, the increase in survival may be acceptable in proposing an alternative to debulking procedures alone.
Topics: Adenocarcinoma, Mucinous; Antineoplastic Agents; Humans; Infusions, Parenteral; Injections, Intraperitoneal; Peritoneal Neoplasms; Pseudomyxoma Peritonei
PubMed: 23490141
DOI: 10.1016/j.jss.2012.12.040 -
Frontiers in Surgery 2020Pseudomyxoma peritonei (PMP) is a rare clinical condition with fatal outcomes, which is characterized by the progressive accumulation of mucinous ascites and peritoneal...
Pseudomyxoma peritonei (PMP) is a rare clinical condition with fatal outcomes, which is characterized by the progressive accumulation of mucinous ascites and peritoneal implants. Some studies have reported the effect of PMP biology on patient outcome. The objective of this study was to analyze published articles focusing on the impact of pathology on the prognosis of PMP patients undergoing debulking. Data from all studies regarding the prognosis of patients, with different pathologies, who underwent debulking surgery were analyzed. We searched PubMed, the Wiley Online Library, Ovid, and the Cochrane Library (through January 2020). Studies were confined to those articles written in English. Five studies were identified, and the differences in 5-year survival rates were analyzed according to the Kaplan-Meier survival curves. The hazard ratios (HRs) of the 5-year survival rates were calculated. The mean and median 5-year survival rates of all patients were 39 and 40%, respectively. The median overall survival was 49.3 months. The mean 5-year survival rates of low-grade PMP was 45.2%. The five studies had sufficient data to calculate HRs from the 5-year survival rates data, and three had HRs lower than 1. The total HRs was 0.54, with a 95% CI between 0.33 and 0.89 ( = 0.01). Among PMP patients receiving debulking surgery who are not able to undergo complete cytoreductive surgery, low-grade biological PMP had a better prognosis than high-grade PMP.
PubMed: 33304920
DOI: 10.3389/fsurg.2020.554910 -
The British Journal of Surgery Feb 2005Pseudomyxoma peritonei, a rare progressive disease process within the peritoneum, is characterized by an abundance of mucinous fluid; if left untreated, the condition is... (Review)
Review
BACKGROUND
Pseudomyxoma peritonei, a rare progressive disease process within the peritoneum, is characterized by an abundance of mucinous fluid; if left untreated, the condition is fatal. The aim of this article is to assess the clinical effectiveness and costs of the Sugarbaker procedure for pseudomyxoma peritonei.
METHODS
A systematic review of the literature up to April 2004 was undertaken, with modelling of costs.
RESULTS
Five retrospective case-series reports met the inclusion criteria. Survival after operation was approximately 95 per cent at 2 years and 60-68 per cent at 10 years, with 41-52 per cent of patients having no evidence of disease at the end of follow-up. A Monte Carlo simulation model estimated the marginal cost for one patient over a maximum of 5 years to be about pound 9700 (standard deviation pound 1300).
CONCLUSION
Evidence of the effectiveness of the Sugarbaker procedure for pseudomyxoma peritonei is limited in quantity and quality, but suggests there may be some benefit for patients. The marginal cost of the operation is about pound 9700, provided that trained and experienced staff are available to perform the procedure.
Topics: Costs and Cost Analysis; Humans; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Postoperative Complications; Pseudomyxoma Peritonei; Surgical Procedures, Operative; Treatment Outcome
PubMed: 15685704
DOI: 10.1002/bjs.4862 -
Frontiers in Oncology 2024Pseudomyxoma peritonei (PMP) was a complex disease that had attracted increasing attention. However, there had been no bibliometric analysis of this disease so far. This...
OBJECTIVE
Pseudomyxoma peritonei (PMP) was a complex disease that had attracted increasing attention. However, there had been no bibliometric analysis of this disease so far. This study aimed to explore the current situation and frontier trend of PMP through bibliometric and visualization analysis, and to indicate new directions for future research.
METHODS
The original research articles and reviews related to the PMP research were downloaded from Web of Science Core Collection on September 11, 2023. CiteSpace (6.2.R4) and VOSviewer(1.6.18) were used to perform bibliometric analysis of the publications, and establish the knowledge map. The data collected was analyzed using the Online Analysis Platform of Bibliometric to evaluate the cooperation of countries in this field.
RESULTS
We identified 1449 original articles and reviews on PMP published between 1998 and 2023. The number of publications on PMP increased continuously. The United States, the United Kingdom and China were the top contributors. The most productive organization was the MedStar Washington Hospital Center. Sugarbaker, Paul H. was the most prolific author and the most cited. Keyword analysis showed that "Pseudomyxoma peritonei", "cancer", "cytoreductive surgery", and "hyperthermic intraperitoneal chemotherapy" were the most common keywords. The earliest and latest used keywords were "mucinous tumors" and "impact", respectively. "classification", "cytoreductive surgery", "appendiceal" were the top 3 strongest citation bursts. The reference "Carr NJ, 2016, " had the highest co-citations.
CONCLUSION
This bibliometric analysis showed an increasing trend in literature related to PMP. The research trends and hotspots identified in this study could guide the future research directions in this field, in order to promote the development of PMP.
PubMed: 38390264
DOI: 10.3389/fonc.2024.1323796 -
Annals of Surgical Oncology Feb 2007The efficacy of cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) for patients with pseudomyxoma peritonei (PMP) remains to be... (Review)
Review
BACKGROUND
The efficacy of cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) for patients with pseudomyxoma peritonei (PMP) remains to be established.
METHODS
Searches for all relevant studies prior to March 2006 were performed on six databases. Two reviewers independently appraised each study using a predetermined protocol. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies.
RESULTS
Ten most recent updates from each institution were included for appraisal and data extraction. There were no randomized controlled trials or comparative studies. All included articles were observational studies without control groups. Five studies were relatively large series (n>or=100). Two studies had relatively long-term follow-up (48 months and 52 months). The median follow-up in the remaining eight studies was shorter than 3 years (range 19-35 months). The median survival ranged from 51 to 156 months. The 1-, 2-, 3- and 5-year survival rates varied from 80 to 100%, 76 to 96%, 59 to 96% and 52 to 96%, respectively. The overall morbidity rate varied from 33 to 56%. The overall mortality rates ranged from 0 to 18%.
CONCLUSIONS
This study reviewed current evidence on CRS and PIC for PMP. Only observational studies were available for evaluation, which demonstrated some promising long-term results, as compared to historical controls. Due to the rarity of this disease, a well-designed prospective multi-institutional study would be meaningful.
Topics: Antineoplastic Agents; Humans; Infusions, Parenteral; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Treatment Outcome
PubMed: 17054002
DOI: 10.1245/s10434-006-9182-x -
Health Technology Assessment... Feb 2004This systematic review examines the clinical and cost-effectiveness of the Sugarbaker procedure for treating pseudomyxoma peritonei (PMP) and the costs of the procedure... (Review)
Review
OBJECTIVES
This systematic review examines the clinical and cost-effectiveness of the Sugarbaker procedure for treating pseudomyxoma peritonei (PMP) and the costs of the procedure in the UK.
DATA SOURCES
Electronic databases, bibliographies of related papers and experts in the field were used as sources for English language studies available up to September 2002.
REVIEW METHODS
Evidence of the clinical effectiveness of the Sugarbaker procedure for PMP was synthesised through a narrative review with full tabulation of results of all included studies. The economic modelling used a Monte-Carlo simulation model populated with UK price data to estimate likely UK costs.
RESULTS
Five retrospective case-series reports assessing the Sugarbaker procedure met the inclusion criteria for the review, although they were found to be of poor quality when judged against standard criteria for assessing methodological standard. There appears to be some benefit for people with PMP who undergo treatment with the Sugarbaker procedure. Commonly reported complications of the Sugarbaker procedure were anastomotic leaks, fistula formation, wound infection, small bowel perforations/obstructions and pancreatitis. One costing study of poor methodological quality and set in the USA was found. This study, together with UK unit price data and expert advice, was used to populate a Monte-Carlo simulation model to estimate the marginal cost of operating a service to provide treatment for PMP using the Sugarbaker technique rather than standard treatment. The results of the Monte-Carlo simulation model showed that the cost for one patient over a maximum of 5 years would be about 9700 British pounds, with a standard deviation of about 1300 British pounds (although costs incurred in setting up the specific service or training the staff were not included). The US study showed a ten-fold higher cost. The Monte-Carlo analysis showed that the variation around the mean was not very high. The most likely factor influencing the variation of the costs was the length of procedure. No sensitivity analysis could be done of the alternative treatment.
CONCLUSIONS
The economic results should be seen as merely an example of the likely marginal costs of the Sugarbaker procedure, as more information about the current alternative is required. Trained and experienced staff are required to implement the procedure and inevitably time and cost will be involved in developing the appropriate teams. Although the procedure requires some specialist equipment and maintenance, such as smoke evacuators, these should have limited effect on setting up the service. PMP is a relatively rare condition with approximately 50 new cases per year in the UK and the impact of an increase in the demand for services should be limited. Evidence is needed for the effectiveness of maximal cytoreductive surgery compared with surgical debulking, using different intraoperative intraperitoneal chemotherapy strategies, and for the effectiveness of treatments in patients who have residual disease following maximal efforts at cytoreduction. Further research involving high-quality prospective cohort studies with economic evaluations would be valuable.
Topics: Adult; Aged; Aged, 80 and over; Costs and Cost Analysis; Female; Humans; Male; Middle Aged; Pseudomyxoma Peritonei; State Medicine; Surgical Procedures, Operative; Treatment Outcome; United Kingdom
PubMed: 14960255
DOI: 10.3310/hta8070 -
Wiener Medizinische Wochenschrift (1946) Dec 2014The objective of this study was to provide an overview of published and ongoing trials of pressurized intraperitoneal chemotherapy (PIPAC) in ovarian cancer. (Review)
Review
OBJECTIVE
The objective of this study was to provide an overview of published and ongoing trials of pressurized intraperitoneal chemotherapy (PIPAC) in ovarian cancer.
DESIGN
The study comprised a systematic literature review.
RESULTS
We identified 10 studies, including 2 ex vivo and in vitro studies, 6 clinical studies, and 2 ongoing clinical trials using PIPAC in women with recurrent ovarian cancer and pseudomyxoma peritonei. Experimental evidence and clinical study data demonstrate that PIPAC increases peritoneal cavity coverage and depth of peritoneal infiltration, and is technically feasible. Occupational safety has been established. PIPAC has demonstrated antitumor activity based on histological, radiological, and clinical evidence. The toxicity of PIPAC is manageable and restricted to Common Terminology Criteria for Adverse Events grade 2-3 events when used without concomitant cytoreductive surgery. Further clinical trials assessing efficacy and dose escalation are ongoing.
CONCLUSIONS
PIPAC is technically feasible, has a safe local and systemic safety profile, and has antitumor activity in women with peritoneal carcinomatosis from recurrent ovarian cancer.
Topics: Aerosols; Animals; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Clinical Trials as Topic; Compressed Air; Feasibility Studies; Female; Genital Neoplasms, Female; Humans; Peritoneal Neoplasms
PubMed: 25249025
DOI: 10.1007/s10354-014-0312-y