Nanoparticle as a novel tool in hyperthermic intraperitoneal and pressurized intraperitoneal aerosol chemotheprapy to treat patients with peritoneal carcinomatosis

The treatment of peritoneal surface malignances has changed considerably over the last thirty years. Unfortunately, the palliative is the only current treatment for peritoneal carcinomatosis (PC). Two primary intraperitoneal chemotherapeutic methods are used. The first is combination of cytoreductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), which has become the gold standard for many cases of PC. The second is Pressurized IntraPeritoneal Aerosol Chemotheprapy (PIPAC), which is promising direction to minimally invasive as safedrug delivery. These methods were improved through multicenter studies and clinical trials that yield important insights and solutions. Major method development has been made through nanomedicine, specifically nanoparticles. Here, we are presenting the latest advances of nanoparticles and their application to precision diagnostics and improved treatment strategies for PC. These advances will likely develop both HIPEC and PIPAC methods that used for in vitro and in vivo studies. Several benefits of using nanoparticles will be discussed including: 1) Nanoparticles as drug delivery systems; 2) Nanoparticles and Near Infrred (NIR) Irradiation; 3) use of nanoparticles in perioperative diagnostic and individualized treatment planning; 4) use of nanoparticles as anticancer dressing's, hydrogels and as active beeds for optimal reccurence prevention; and 5) finally the curent in vitro and in vivo studies and clinical trials of nanoparticles. The current review highlighted use of nanoparticles as novel tools in improving drug delivery to be effective for treatment patients with peritoneal carcinomatosis

Consensus statement for treatment protocols in pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Objectives: Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics. Methods: The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance). Results: Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m(2)) and cisplatin (10.5 mg/m(2)) was endorsed by 20/ 22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m(2) (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of >= 8/10. Conclusions: The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research

Utility of organoids to select chemotherapeutic drugs for colorectal peritoneal metastasis

[Background]: •Peritoneal metastasis of colorectal origin or colorectal carcinomatosis is a disease with limited therapeutic options and a poor prognosis. •Overall survival of patients with colorectal peritoneal metastasis has improved thanks to the combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC) plus systemic chemotherapy. •Results obtained with oxaliplatin and mitomycin, the two most commonly used drugs, are far from the optimal option and the better treatment for these patients is still an unmet clinical need. Patient-derived organoids have been established from an increasing number of tumor types to study the tumorigenic process and in several cases their value in drug sensitivity testing and prediction of treatment responses[Materials and Methods]: Using as an example one case of a patient with peritoneal metastasis of colorectal origin we present how organoids are a promising method to test chemosensitivity in this cell models from the own patient cancer cells, as the quintessential of personalized therapy, Organoids from peritoneal nodules were established following the protocol common to primary colorectal tumors. At the eight passage, eight weeks after surgery, organoids were disaggregated and seeded on 24-well plates (250 organoids/well). On 24 h incubation, organoids were subjected to single treatment with 5-FU, SN-38 (7-ethyl-10-hydroxycamptothecin, the active metabolite of the DNA topoisomerase I inhibitor irinotecan) or oxaliplatin. Seven doses of drug (in triplicate) were used. Each one covered the range commonly used in in vitro assays.[Results]: On day 4 of treatment, the size of organoids was smaller in cultures treated with 5-FU and SN-38 . This result was less evident in the case of cultures treated with oxaliplatin. According to the microscopy images, 5-FU and SN-38 displayed relatively strong cytotoxicity (IC50 = 10 μM and IC50 = 0.015 μM, respectively). In contrast, the response to oxaliplatin was much lower and no IC50 was reached in the assays. DNA was isolated from a culture plate for targeted sequencing mutational analysis of organoids using the Oncomine Comprehensive Assay v3.(ThermoFisher) It revealed mutations in two genes, PIK3CA (c.3140A>G, rs121913279) and SMAD4 (c.1082G>T, rs377767347). Interestingly, mutation in these genes is associated with mucinous histology and aggressiveness . Together, these data suggest that at least the original implant had acquired resistance to oxaliplatin, while it remained sensitive to irinotecan and 5-FU, which supports therapeutic options based on single or combined treatments with these two drugs[Conclusions]: The present study shows that organoids are a feasible approach to improve in a personalized manner the therapeutic management of patients with colorectal carcinomatosis, to select the most appropriate drug for HIPEC or PIPAC therapy

Nutritional assessment in surgical oncology: An ESSO-EYSAC global survey

Introduction: The majority of cancer patients report malnutrition, with a significant impact on patient's outcome. This study aimed to compare how nutritional assessment is conducted across different surgical oncology sub-specialties. Methods: Survey modules were designed for breast, hepato-pancreato-biliary (HPB), upper-gastrointestinal (UGI), sarcoma, peritoneal and surface malignancies (PSM) and colorectal cancer (CRC) surgeries to describe 4 domains: participants' setting, evaluation of clinical factors, use of screening tools and clinical practice. Results were compared among sub-specialties and according to human development index (HDI) in the largest cohorts. Results: Out of 457 answers from 377 global participants (62% European), 35.0% were from breast and 28.9% were from CRC surgeons. Although MDTs management is consistently reported (64-88%), the presence of a nutritionist/dietician ranges from 14.1% to 44.2%. Breast surgeons seldom evaluate albumin (25.6%) and weight loss (30.6%), opposite to HPB, PSM and UGI groups (>70%, p 0.044). Overall, responders declared that the use of screening tools is largely neglected, that nutritional status is often assessed by the surgeons and that nutrition is not consistently modified according to risk factors (range among groups respectively: 1.9%-25.6%, 33.1%-51.4%, 33.1%-60.5%). Less than 20% of breast surgeons assess patients before/after surgery, comparing to >60% of PSM surgeons. However, no statistical differences were documented comparing groups for the majority of the items of the 4 domains. Nutritional evaluation is more often conducted by breast surgeons in medium/low HDI countries comparing very high/high HDI (p 0.04). Conclusions: Nutritional assessment is largely neglected. These results identify target-issues for the implementation of clinical practice. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved

Consensus statement for treatment protocols in pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Objectives: Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics. Methods: The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance). Results: Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m(2)) and cisplatin (10.5 mg/m(2)) was endorsed by 20/ 22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m(2) (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of >= 8/10. Conclusions: The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research

The delphi and GRADE methodology used in the PSOGI 2018 consensus statement on pseudomyxoma peritonei and peritoneal mesothelioma

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%-100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future

Patterns of peritoneal dissemination and response to systemic chemotherapy in common and rare peritoneal tumours treated by cytoreductive surgery: study protocol of a prospective, multicentre, observational study

Introduction: Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. Methods and analysis: There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied. Ethics and dissemination: The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128). Trial registration number: CTRI/2020/09/027709; Pre-results