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Air pollution represents a major health problem and an economic burden. In recent years, advances in air pollution research has allowed particle fractionation and identification of secondary organic aerosol (SOA). SOA is formed from either biogenic or anthropogenic emissions, through a mass transfer from the gaseous mass to the particulate phase in the atmosphere. They can have deleterious impact on health and the mortality of individuals with chronic inflammatory diseases. The pleiotropic effects of SOA could involve different and interconnected pathogenic mechanisms ranging from oxidative stress, inflammation, and immune system dysfunction. The purpose of this review is to present recent findings about SOA pathogenic roles and potential underlying mechanisms focusing on the lungs; the latter being the primary exposed organ to atmospheric pollutants.

The differentiation between reactive mesothelial hyperplasia (RMH) and diffuse malignant peritoneal mesothelioma (DMPM) is challenging especially when applied on peritoneal small samples. The use of BRCA-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) immunostains is familiar to identify malignant mesothelial proliferation. Recently, nuclear 5-hydroxymethylcytosine (5-hmC) was reported to be a new recognition tool of pleural mesothelial malignancy on surgical specimens. However, application of 5-hmC immunostaining has not yet studied in peritoneal specimens from small biopsies or cytology cell-blocks. The aim was to assess the diagnostic accuracy of this new marker combination to distinguish DMPM from RMH in biopsies and cell-blocks. Seventy-five cases were analyzed; among which, 38 were of cytological specimens including 6 RMH and 32 DMPM, and 37 tissue biopsies with 7 RMH and 30 DMPM. BAP1, MTAP, and 5-hmC immunostains were performed on all cases. RMH cases exhibited a retained staining with all immunostains. Among DMPM, BAP1 was lost in 71.8% of cytology cell-blocks and 66.7% of biopsies. MTAP was lost in 40.6% of cytology cell-blocks and 33.3% of biopsies. 5-hmC was lost in 40.6% of cytology cell-blocks and 30% of biopsies. The combination of BAP1, MTAP, and 5-hmC showed the best accuracy in differential diagnosis between RMH and DMPM (sensitivity = 0.84, specificity = 1 in cytology cell-blocks; sensitivity = 0.90, specificity = 1 in biopsy). The best diagnostic combination in peritoneal cytology effusion fluids and biopsies samples provided by BAP1, MTAP, and 5-hmC should be applied on a diagnostic step-wise algorithm by pathologists involved into the management of DMPM, because of their therapeutic implications.

This retrospective multicenter cohort study compared the feasibility and safety of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-Ox) with or without intraoperative intravenous 5-fluorouracil (5-FU) and leucovorin (L). Our study included consecutive patients with histologically proven unresectable and isolated colorectal peritoneal metastases (cPM) treated with PIPAC-Ox in seven tertiary referral centers between January 2015 and April 2020. Toxicity events and oncological outcomes (histological response, progression-free survival, and overall survival) were compared between patients who received intraoperative intravenous 5-FU/L (PIPAC-Ox + 5-FU/L group) and patients who did not (PIPAC-Ox group). In total, 101 patients (263 procedures) were included in the PIPAC-Ox group and 30 patients (80 procedures) were included in the PIPAC-Ox + 5-FU/L group. Common Terminology Criteria for Adverse Events v4.0 grade 2 or higher adverse events occurred in 48 of 101 (47.5%) patients in the PIPAC-Ox group and in 13 of 30 (43.3%) patients in the PIPAC-Ox + 5-FU/L group (p = 0.73). The complete histological response rates according to the peritoneal regression grading score were 27% for the PIPAC-Ox + 5-FU/L group and 18% for the PIPAC-Ox group (p = 0.74). No statistically significant differences were observed in overall or progression-free survival between the two groups. The safety and feasibility of PIPAC-Ox + 5-FU/L appears to be similar to the safety and feasibility of PIPAC-Ox alone in patients with unresectable cPM. Oncological outcomes must be evaluated in larger studies.

Introduction This document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) ( www.tncd.org ). Methods All French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence. Results AT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies. Conclusion These recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.

Background and aim The greater omentum(GO) is a common site of residual disease in patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer. The presence of tumor in the GO could predict presence of disease in other peritoneal regions. The goal of this study was to perform a correlation between the greater-omentum lesion-score(GOLS) and presence of disease in different peritoneal regions and determine its potential utility in guiding interval cytoreductive surgery(CRS). Methods This prospective study included 134 patients undergoing interval CRS from July 1, 2018 to June 30, 2020. Each region of Sugarbaker's Peritobneal Cancer Index(PCI) was given a lesion score(LS) from 0 to 3 according to the diameter of the largest tumor in the region. The GOLS was recorded separately from other structures in the region. Correlation between the GOLS and surgical and pathological LS in each region was performed. Results As the GOLS increased, the incidence of disease(surgical LS) in other regions of the peritoneal cavity increased. Receiver operating characteristic(ROC) curves showed area under curve more than 80% for regions 1–2 and 7–8 indicating a high probability of disease in these regions in patients with GOLS 1–3. The positive predictive value(PPV) of preoperative imaging for GOLS was 95.7%. No cut-off of the GOLS could predict presence of disease on pathology with more than 70% accuracy. Conclusions Presence of disease in the GO warrants performing upper abdominal exploration and/or cytoreduction and interval CRS should be planned accordingly in these patients. Imaging has a high PPV in detecting disease in the GO.

Introduction: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. Materials and methods: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. Results: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. Conclusion: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated. (c) 2021 Published by Elsevier Ltd.

Introduction Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique for the treatment of initially unresectable peritoneal carcinomatosis (PC). Our objective was to compare the results of PIPAC associated with systemic chemotherapy (PIPAC_CHEM) with those of systemic chemotherapy alone (ONLY_CHEM) in patients with gastric PC without metastasis other than peritoneal, and the WHO performance status Methods This was a retrospective, single center, comparative non-randomized study. Seventeen PIPAC_CHEM patients were compared to 29 ONLY_CHEM patients. The primary endpoint was overall survival at 6 months from diagnosis of PC. Results Ninety-eight patients were screened and 46 were included (PIPAC_CHEM, n = 17; ONLY_CHEM, n = 29). The PIPAC_ CHEM population was significantly younger (median 64 years [56; 68] vs 74 years [61; 79]; p = 0.0054). Median PIPAC session per patient is 2 [1-3]. Six-month survival was significantly higher in the PIPAC_CHEM group than in the ONLY_CHEM group 16/17 (94.1% [65-99.2]) vs 19/29 (65.5% [45.4-79.7]), respectively; p = 0.029. Over the entire follow-up, median survival [95% CI] was 12.8 months [7.2-34.3] with PIPAC vs 9.1 months [5.4-11.5] without, p = 0.056. At 6 months, median length of additional hospitalization was significantly less for PIPAC_CHEM (median 2 days [2-7]) than without PIPAC (median 11 days [3-21]) (p = 0.045). Conclusion The overall survival at 6 months after the diagnosis of carcinomatosis was significantly better for PIPAC_CHEM patients. This difference appears to continue until at least 18 months. At 6 months, days of additional hospitalization was significantly less in the PIPAC_CHEM group. Trial registration Clinicaltrials.gov Identifier: NCT 04,879,953.

Background The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. Methods All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. Results In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P Conclusion In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.

International audience; Objective: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures. Background: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality. Methods: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram. Results: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%). Conclusion: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions.

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. A recently described nuclear-grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The present study was undertaken to validate this grading system in epithelioid malignant peritoneal mesothelioma (EMPM) and to compare to combined grade, including nuclear atypia, mitotic count, and tumor necrosis. Cases of EMPM, from 1995 to 2018, were analyzed from 7 French institutions from RENAPE network. Solid growth, tumor necrosis, nuclear atypia, and mitotic count were evaluated by at least 3 pathologists from the RENAPATH group. The predictions in terms of OS and PFS of nuclear grade and combined grade were analyzed. Nuclear grade was computed combining nuclear atypia score and mitotic count into a grade of I–III. Another system combining nuclear atypia score, mitotic score, and tumor necrosis was evaluated and defined as a combined grade I–III. A total of 138 cases were identified. The median follow-up was 38.9 months (range: 1.1–196.6). Nuclear and combined grades III were independently associated with a shorter OS (p

Peritoneal surface malignancies (PSMs) are usually associated with a poor prognosis. Nonetheless, in line with advances in the management of most abdominopelvic metastatic diseases, considerable progress has been made over the past decade. An improved understanding of disease biology has led to the more accurate prediction of neoplasia aggressiveness and the treatment response and has been reflected in the proposal of new classification systems. Achieving complete cytoreductive surgery remains the cornerstone of curative-intent treatment of PSMs. Alongside centralization in expert centres, enabling the delivery of multimodal and multidisciplinary strategies, preoperative management is a crucial step in order to select patients who are most likely to benefit from surgery. Depending on the specific PSM, the role of intraperitoneal chemotherapy and of perioperative systemic chemotherapy, in particular, in the neoadjuvant setting, is established in certain scenarios but questioned in several others, although more prospective data are required. In this Review, we describe advances in all aspects of the management of PSMs including disease biology, assessment and improvement of disease resectability, perioperative management, systemic therapy and pre-emptive management, and we speculate on future research directions.

International audience; Aim Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report 3-year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial. Method PRODIGE 22 was a randomized multicentre phase II trial in high-risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild-type RAS patients, a third arm testing perioperative FOLFOX-cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and time to recurrence (TTR). Results Overall, 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients represented our intention-to-treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow-up was 54.3 months. Three-year OS was 90.4% in both arms [hazard ratio (HR) = 0.85], 3-year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed. Conclusion Perioperative FOLFOX has no detrimental effect on long-term oncological outcomes and may be an option for some patients with locally advanced CC.

Background Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer. Methods Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively. Results A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P Conclusions This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.

Background PIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment. Methods All patients diagnosed with unresectable PM who became resectable throughout PIPAC treatment were included. Outcome criteria were adverse events following PIPAC procedure and rate of secondary CRS and HIPEC. Results Four hundred thirty-seven PIPAC were done in 146 consecutive patients. Among them, 26 patients (17.8%) who underwent 76 PIPAC were scheduled for CRS and HIPEC after reduction of the peritoneal burden. PM were from gastric, peritoneal mesothelioma, ovarian, colorectal and small bowel in 13, 7, 4, 1 and 1 patients, respectively. At the time of the first PIPAC, median age was 58.6 years (32–76.3). Median PCI was 16 (1–39). All patients had systemic chemotherapy in between PIPAC session. Median consecutive PIPAC procedure was 3 (1–8). Complications occurred in 3 PIPAC session (4%) and there was no major complication (CTCAE III or higher). Complete CRS and HIPEC was achieved in 21 patients of the 26 scheduled (14.4%). The remaining 5 patients were considered unresectable at the exploratory laparotomy. Among patients who underwent CRS and HIPEC, with median follow-up of 7 (1–26) months, 14 patients (66.7%) were alive without recurrence, 2 patients (9.5%) were alive with recurrence and 5 patients (23.8%) died. Conclusions Complete CRS and HIPEC can be achieved in strictly selected patient with unresectable PM at diagnosis after repeated PIPAC session with palliative intent.

Background Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. Methods The RENAPE database (French expert centers network) was analyzed over a 1999–2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. Results Overall 60 patients (50 women) were included with a median PCI of 10 (4–14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7–95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12–1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). Conclusion MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.

Peritoneal metastasis (PM) of gastric cancer (GC) is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyse a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics.We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven PM of GC, treated with CRS and HIPEC, and overall survival5 years. Patient, tumour, and therapeutic details were collected and analysed.From an analysis of 448 patients treated between 1994 and 2014, a total of 28 patients with a mean age of 53.0 years and mean PCI of 3.3 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and PCI6 were present in 22/28 patients. 12/28 patients developed at a median of 9.6 years tumour recurrence, and was associated with inferior median overall survival compared to patients without recurrence (8.8 years vs. not reached; p = 0.002).Long-term survival and even cure are possible in patients with PM of GC treated with CRS and HIPEC. Completeness of cytoreduction and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.

Background Colorectal cancer (CRC) treatment in patients with peritoneal metastases is complex. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are under debate. The aim of this study was to assess the consensus among international experts for decision-making regarding CRS/HIPEC in CRC patients. Materials and methods Twelve of 15 experts provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Based on the objective consensus methodology, the results were transformed into decision trees, which then provided information on the consensus and discordance. Results There was only one scenario in which the consensus on performing HIPEC reached 100%, which was when treating young patients with complete cytoreduction and a peritoneal carcinomatosis index (PCI) of less than 16 in the presence of certain risk factors (RFs). Five major decision criteria were identified and displayed: age, PCI, completeness of cytoreduction (CC), extent of extraperitoneal metastases (EoM) and, in the case of nonverified extraperitoneal metastases, further RFs. There was consensus to refrain from using HIPEC in older patients with a high PCI, and the consensus further increased when addressing incomplete cytoreduction and extensive EoM. Conclusion A definite consensus concerning the use of HIPEC was only determined for very selected scenarios. These findings can be used for general guidance, but due to the heterogeneity of each individual situation and the impracticality to present this information through decision trees, as well as the unclear future of the role of HIPEC in the adjuvant setting, a one-on-one transfer to daily clinical practice cannot be achieved.

Background Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part I of the guidelines highlights preoperative and intraoperative management. Methods The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations. Results Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items, No consensus could be reached regarding the preemptive use of fresh frozen plasma. Conclusion The present ERAS recommendations for CRS±HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS±HIPEC and to prospectively evaluate recommendations in clinical practice.

Background Advanced cancer patients often experience multiple symptoms at a same time. This might lead to polypharmacy and increase adverse events representing major threats to the quality of health care, especially in palliative care situations. Mirtazapine, an antidepressant agent, has been suggested as a potential relevant drug to alleviate multiple cancer-related symptoms at a same time. Therefore, the present study aims to assess the effectiveness of mirtazapine in alleviating multiple symptoms at a same time in advanced cancer patients suffering from a major depressive episode compared to a group receiving escitalopram, another antidepressant agent. Methods Multicentre, prospective, randomized, controlled trial in 12 palliative care services in France. The study will be based on a mixed-method methodology using parallel groups, of oral mirtazapine compared with oral escitalopram, with a 56 day follow-up. The primary outcome will be an improvement of the Global health Status (issued from the EORTC-QLQ-C30) on day 56. 418 participants will be clinically followed-up on day 7 and 56 and will have a telephonic assessment on days 14 and 28. A sub-sample of participants will be invited to take part in semi-structured qualitative interviews at baseline and day 56. For the qualitative part, purposeful sampling will be used. Discussion This study will provide evidence for the pharmaceutics management of poly-symptomatology in advanced cancer patients. This could lead to important changes in the management of those patients by using a single molecule to alleviate multiple symptoms at a same time, potentially improving medication adherence, symptoms’ control, and reducing the risk of medications adverse events. Trial registration Trial registration: NCT04763135. Registered 18 March 2021.

Background & objective: Major abdominal surgery morbidity can reach 50%. Prehabilitation has shown promising results in decreasing complications. However, it is unknown if prehabilitation can have a positive effect specifically after major abdominal surgery. The goal of this study was to evaluate the feasibility and safety of a prehabilitation program before major abdominal surgery. Methods: All patients evaluated for major abdominal surgery between February and April 2018 were eligible. A 4-week trimodal prehabilitation program combining physical therapy, nutritional support and psychological preparation was set up. Results: Among 106 patients evaluated for major abdominal surgery during the study period, 60 were included in the prehabilitation program. No cardiovascular events occurred during prehabilitation. The 6-min walking distance increased significantly (+45 m, increase of 9.3%, p = 0.008) after prehabilitation (and before the operation). Anxiety, depression, and several quality of life (QoL) items improved. Postoperative 90-day mortality and morbidity were 3.4% and 48%, respectively. Median hospital length of stay, and intensive care unit length of stay were 14 and 6 days, respectively. For 19 patients readmitted, the treatment was medical, radiological, or surgical, for 11, 5, and 3 patients, respectively. Conclusions: Prehabilitation before major abdominal surgery is feasible, safe, and improve patients’ functional reserves, QoL, and psychological status.

Patients undergoing cytoreductive surgery for colorectal peritoneal metastases who have a pathologic complete response (pCR) to neoadjuvant chemotherapy experience a significantly longer survival than those with residual disease. This response is known only after surgery. This study aimed to examine clinical and radiologic predictors of a pCR. From July 2018 to December 2019, the study prospectively enrolled 120 patients. The clinical and radiologic findings were compared between patients with and without a pCR. A protocol for pathologic evaluation was followed. A pCR was observed in 34 patients (28.3%). Receiver operating characteristic (ROC) curves showed that patients with a surgical Peritoneal Cancer Index (sPCI) of 3 or lower had an 80% probability of experiencing a pCR, and that patients with a radiologic PCI (rPCI) of 2 or lower had a 70% probability of experiencing a pCR. A pCR was correctly predicted for 47% of the patients by imaging and for 44.4% of the patients by surgical evaluation. The site of primary tumor, the timing of peritoneal metastasis (PM), histology, tumor marker positivity, and mutations in known poor prognostic genes (KRAS) did not differ between the patients with and those without pCR. The primary tumor showed residual disease in 23.5% and regional nodes in 26.4% of the patients with pCR. The rPCI and sPCI concurred with a pCR in less than 50% of the patients. The patients with a lower PCI had greater concordance. An sPCI of 3 or lower was predictive of a pCR in 80% of the patients. The impact of KRAS mutations on pCR should be evaluated in a larger series. The predictors of pCR and response to systemic chemotherapy should be incorporated in prognostic scores used to select patients for surgery.

Background Complete cytoreductive surgery of macroscopic tumor is a potentially curative treatment for patients with colorectal peritoneal metastases. Objective This study aims to determine the risk of microscopic tumor involvement of the greater omentum in patients with normal-looking omentum at the time of cytoreductive surgery for colorectal peritoneal metastases. Design This was a cohort study. Settings The prospective BIG-RENAPE database (NCT02823860) was analyzed. Patients All patients who underwent a complete cytoreductive surgery with greater omentectomy for colorectal peritoneal metastases at a single institution between January 2005 and December 2017 were included. Main outcome measure Data regarding involvement of the greater omentum were extracted from surgical and pathological records. Results Of 337 patients who underwent cytoreductive surgery for colorectal peritoneal metastases, 241 (71.51%) presented macroscopic omental invasion. Among the 96 patients who underwent a complete cytoreductive surgery with no macroscopic evidence of disease in the greater omentum during surgical exploration, 17 patients (17.70%) had microscopic evidence of tumor in the omentum. Patients with pathological evidence of omental tumor involvement were more likely to have a higher peritoneal cancer index (median 9 vs 4, p = 0.006). Limitations No survival analysis could be provided regarding the impact of omentectomy. Conclusion In patients with a normal-looking omentum during surgery for colorectal peritoneal metastases, microscopic tumor was present in 17%. Routine greater omentectomy should be considered in these patients to ensure complete cytoreduction. See Video Abstract at http://links.lww.com/DCR/B262.ClinicalTrials.gov Identifier: NCT02823860 RIESGO DE METASTASIS OMENTALES EN PACIENTES SOMETIDOS A CIRUGIA CITORREDUCTORA, POR METASTASIS PERITONEALES COLORRECTALES: La cirugia citorreductora completa del tumor macroscopico, es un tratamiento potencialmente curativo, en pacientes con metastasis peritoneales colorrectales.Determinar el riesgo de afectacion tumoral microscopica del epiplon mayor, en pacientes con epiplon de aspecto normal, al momento de la cirugia citorreductora por metastasis peritoneales colorrectales.Este fue un estudio de cohorte.Se analizo la base de datos prospectiva BIG-RENAPE (NCT02823860).Se incluyeron a todos los pacientes sometidos a una cirugia citorreductora completa con omentectomia mayor, por metastasis peritoneales colorrectales, de una sola institucion, entre enero de 2005 y diciembre de 2017.Se extrajeron los datos de la afectacion del epiplon mayor, de los registros quirurgicos y patologicos.De 337 pacientes sometidos a cirugia citorreductora por metastasis peritoneales colorrectales, 241 (71.51%) presentaron invasion omental macroscopica. Entre los 96 pacientes sometidos a cirugia citorreductora completa, sin evidencia macroscopica de enfermedad en el epiplon mayor, durante la exploracion quirurgica, 17 pacientes (17,70%) tuvieron en el epiplon, evidencia microscopica de tumor. Los pacientes con evidencia patologica de afectacion del tumor omental, fueron mas propensos a tener un indice de cancer peritoneal mas alto (mediana 9 frente a 4, p = 0,006).No se pudo obtener ningun analisis de supervivencia, sobre el impacto de la omentectomia.En pacientes con epiplon de aspecto normal, durante la cirugia por metastasis peritoneales colorrectales, estuvo presente el tumor microscopico, en el 17% de los casos. Se debe considerar una omentectomia mayor de rutina en estos pacientes, para asegurar una citorreduccion completa. Consulte Video Resumen http://links.lww.com/DCR/B262.Identificador de ClinicalTrials.gov: NCT02823860.

International audience; Toll-like receptor 3 (TLR3) is an immune receptor that behaves like a death receptor in tumor cells, thereby providing an original target for cancer therapy. The therapeutic potential of TLR3 targeting in malignant mesothelioma, an aggressive and incurable neoplasia of the pleura and peritoneum, has so far not been addressed. We investigated TLR3 expression and sensitivity of human mesothelioma cell lines to the synthetic dsRNA Poly (I:C), alone or in combination with cisplatin, the gold standard chemotherapy in mesothelioma. Activation of TLR3 by Poly(I:C) induced apoptosis of 4/8 TLR3-positive cell lines but not of TLR3-negative cell lines. The combined cisplatin/Poly(I:C) treatment enhanced apoptosis of 3/4 Poly(I:C)-sensitive cell lines and overcame resistance to Poly(I:C) or cisplatin alone in 2/4 cell lines. Efficacy of the combined treatment relied on cisplatininduced downregulation of c-FLIP, the main regulator of the extrinsic apoptotic pathway, leading to an enhanced caspase-8-mediated pathway. Of note, 6/6 primary cell samples isolated from patients with peritoneal mesothelioma expressed TLR3. Patient-derived cells were sensitive to Poly(I:C) alone while the combined cisplatin/Poly(I:C) treatment induced dramatic cell death. Our findings demonstrate that TLR3 targeting in combination with cisplatin presents an innovative therapeutic strategy in mesothelioma.

The surgical peritoneal cancer index (sPCI) is calculated based on a subjective evaluation of the extent of peritoneal disease during surgery. The pathologic PCI (pPCI) may be a more accurate and objective method for determining the PCI. This study aimed to compare the sPCI and pPCI and to study the potential pitfalls and clinical implications of using the pPCI. This prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). The pPCI was calculated for each patient and compared with the sPCI. The impact of potential confounding factors on the difference between pPCI and sPCI was evaluated. Among 191 patients undergoing CRS at four centers, the pPCI and sPCI were concordant for 37 patients (19.3%). The pPCI was lower than the sPCI for 125 patients (65.4%) and higher for 29 patients (15.1%). The concordance between the two groups was maximum for gastric cancer (38.8%) and colorectal cancer (27.6%) and least for mesothelioma (6.7%) and rare primary tumors (5.6%) (p = 0.04). The difference was 0 to 3 points for 119 patients (62.3%), 4 to 5 points for 27 patients (14.1%), and more than 5 points for 45 patients (23.5%). The rate of concordance was not influenced by the use of neoadjuvant chemotherapy (NACT) (p = 0.4), but the difference was greater when NACT was used (p = 0.03). The pPCI strongly differs from the sPCI for patients undergoing CRS for peritoneal disease and may provide a more accurate evaluation of the peritoneal disease extent. Further studies are needed to determine its prognostic value compared with sPCI, and consensus guidelines are needed for calculating it.

Background: Incisional hernias can be associated with pain or discomfort. Surgical repair especially mesh reinforcement, may likewise induce pain. The primary objective was to assess the incidence of pain after hernia repair in patients with and without pre-operative pain or discomfort. The secondary objectives were to determine the preferred mesh type, mesh location and surgical technique in minimizing postoperative pain or discomfort. Materials and methods: A registry-based prospective cohort study was performed, including patients undergoing incisional hernia repair between September 2011 and May 2019. Patients with a minimum follow-up of 3–6 months were included. The incidence of hernia related pain and discomfort was recorded perioperatively. Results: A total of 1312 patients were included. Pre-operatively, 1091 (83%) patients reported pain or discomfort. After hernia repair, 961 (73%) patients did not report pain or discomfort (mean follow-up = 11.1 months). Of the pre-operative asymptomatic patients (n = 221), 44 (20%, moderate or severe pain: n = 14, 32%) reported pain or discomfort after mean follow-up of 10.5 months. Of those patients initially reporting pain or discomfort (n = 1091), 307 (28%, moderate or severe pain: n = 80, 26%) still reported pain or discomfort after a mean follow-up of 11.3 months postoperatively. Conclusion: In symptomatic incisional hernia patients, hernia related complaints may be resolved in the majority of cases undergoing surgical repair. In asymptomatic incisional hernia patients, pain or discomfort may be induced in a considerable number of patients due to surgical repair and one should be aware if this postoperative complication.

Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry.A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed.The analysis included 83 patients. After a median follow-up of 47 months, the median overall survival (OS) was 34.6 months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications.CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are needed to confirm CRS and HIPEC as the gold standard in this pathology.

PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a minimally invasive approach relying on physical principles for improving intraperitoneal drug delivery, including optimizing the homogeneity of drug distribution through an aerosol. Feasibility and safety of the new approach are now consolidated and data on its effectiveness are continuously increasing. Although any surgical procedure associated with PIPAC had always been discouraged due to the high risk of complications, surgical practice is constantly changing: with growing expertise, more and more surgical teams associate PIPAC with surgery. PLUS study is part of the retrospective international cohort studies including 10 centers around the world (India, Italy, France, Germany, Belgium, Russia, Saudi Arabia, Switzerland) and 96 cases of combined approaches evaluated through a propensity score analysis. the procedures most frequently associated with PIPAC were not only adhesiolysis, omentectomy, adnexectomy, umbilical/inguinal hernia repairs, but also more demanding procedures such as intestinal resections, gastrectomy, splenectomy, bowel repair/stoma creation. Although the evidence is currently limited, PLUS study demonstrated that PIPAC associated with additional surgical procedures is linked to an increase of surgical time (p < 0.001), length of stay (p < 0.001) and medical complication rate (p < 0.001); the most frequently reported medical complications were mild or moderate in severity, such as abdominal pain, nausea, ileus and hyperthermia. No difference in terms of surgical complications was registered; neither reoperation or postoperative deaths were reported. these results suggest that PIPAC can be safely combined in expert centers with additional surgeries. Widespread change of practice should be discouraged before the results of ongoing prospective studies are available.

Objective To investigate the benefit of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of endometrial peritoneal carcinomatosis compared to CRS alone. Methods We conducted a retrospective multicentre study of patients from experienced centres in treating peritoneal malignancies from 2002 to 2015. Patients who underwent surgery for peritoneal evolution of endometrial cancer (EC) were included. Two groups of 30 women were matched and compared: “CRS + HIPEC” which used HIPEC after CRS, and “CRS only” which did not use HIPEC. We analysed clinical, pathologic and treatment data for patients with peritoneal metastases from EC. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS). Results In “CRS plus HIPEC” group, 96.7% of women were treated for recurrence, while in “CRS only” 83.3 were treated for primary disease. There was no significant difference between Peritoneal Carcinomatosis Index at laparotomy or Completeness of Cytoreduction score. Grade III and IV complications rates did not significantly differ between “CRS plus HIPEC” group and “CRS only” group (20.7% vs 20.7%, p = 0.739). Survival analysis showed no statistical difference between both groups. Median OS time was 19.2 months in “CRS plus HIPEC” group and 29.7 months in “CRS only” group (p = 0.606). Median PFS survival time was 10.7 months in “CRS plus HIPEC” group and 13.1 months in “CRS only” group (p = 0.511). Conclusion The use of HIPEC combined to CRS did not have any significance as regard the DFS and OS over CRS alone in patients with primary or recurrent peritoneal metastasis of endometrial cancer.

Objective Diffuse malignant peritoneal mesothelioma (DMPM), represents 30% of all malignant mesothelioma, and is characterised by a difficult diagnosis and different presentations. Immunohistochemistry has improved the diagnostic sensitivity and specificity in the differential diagnosis between metastatic adenocarcinoma and malignant mesothelioma, and loss of BRCA-1-associated protein 1 (BAP1) expression is correlated with BAP1 somatic or constitutional genetic defects. Furthermore, cyclin-dependent kinase inhibitor 2A (CDKN2A) is frequently lost in DMPM. In the present study, we assessed the value of integrating BAP1 in the panel of antibodies used for the diagnosis of DMPM in cytological samples. Since p16 fluorescent in situ hybridisation (FISH) assay could constitute an additional useful adjunct, results of BAP1 immunostaining and p16 FISH assays have been compared. Methods Forty-eight DMPM patients and 71 peritoneal carcinomatosis patients were included. BAP1 immunohistochemical and CDKN2A FISH techniques were performed on tissue specimens of DMPM (n = 48) and peritoneal carcinomatosis (n = 71) then on cell-block of DMPM (n = 16), peritoneal carcinomatosis (n = 25) and peritoneal benign effusion (n = 5). Results Loss of BAP1 expression was observed in 56.3% of DMPM while none of the peritoneal carcinoma specimens showed BAP1 loss of expression. CDKN2A loss was observed in 34.9% DMPM and 2.1% peritoneal carcinoma. Although BAP1 immunostaining was successful in 100% of cytological DMPM samples, CDKN2A deletion status could be obtained for 75% of DMPM cases. Conclusion BAP1 immunostaining represents an objective and reproducible diagnostic biomarker for peritoneal mesothelioma in effusion cytology specimens and should be preferred to CDKN2A FISH analysis on these precious samples.

Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes.

Recent technological advances coupled with our improved understanding of the molecular and cellular mechanisms associated with cancer development have enabled better overall patient care. Among the newly identified biomarkers such as circulating tumor DNA or circulating tumor cells, hPG

Importance Early discharge after colorectal surgery has been advocated. However, there is little research evaluating clinical and/or laboratory criteria to determine who can be safely discharged early. Objective To evaluate the diagnostic performance of a C-reactive protein (CRP) level combined with 4 clinical criteria in ruling out an anastomotic leak and therefore allowing an early discharge on postoperative day 2 or 3. Design, Setting, and Participants This prospective, single-center cohort study was performed between February 2012 and July 2017. All consecutive adult patients undergoing laparoscopic colorectal surgery were included. All patients were followed up for 30 days postoperatively. Data analysis was performed in May 2021. Exposures Whether the 5 discharge criteria were fulfilled on postoperative day 3 (or day 2 for patients discharged on day 2). Fulfillment was defined as a CRP level less than 150 mg/dL on the day of discharge, a return of bowel function, tolerance of a diet, pain less than 5 of 10 on a visual analog scale, and being afebrile during the entire stay. Main Outcomes and Measures The primary outcome measurement was the diagnostic performance of the 5 discharge criteria in anticipating anastomotic leak development. The diagnostic performance of CRP level alone and 4 clinical criteria alone was also evaluated. Secondary measures were anastomotic leaks and mortality rates up to postoperative day 30. A discharge was successful if the patient left the hospital on postoperative day 2 or 3 without any complications or readmissions. Results A total of 287 patients were included (median [IQR] age, 58 [20] years; 141 men [49%] and 146 women [51%]). Mortality was 0%. There were 17 anastomotic leaks, of which 2 were on day 1 and were excluded. A total of 128 patients fulfilled all criteria, and 125 did not, including 34 for whom data were missing. Two leaks occurred in patients who had fulfilled all criteria vs 13 leaks in patients who did not (hazard ratio, 0.15 [95% CI, 0.03-0.69];P = .01). Seventy-six of 128 patients (59.4%) were discharged successfully by postoperative day 3. The negative predictive value in ruling out an anastomotic leak was at least 96.9% for CRP alone (96.9% [95% CI, 93.3%-98.8%]), the 4 clinical criteria (98.4% [95% CI, 95.3%-99.7%]), and all 5 criteria combined (98.4% [95% CI, 94.5%-99.8%]). False-negative rates were 40% (95% CI, 16.3%-67.7%) for CRP level alone, 20% (95% CI, 4.3%-48.1%) for the other 4 criteria, and 13.3% (95% CI, 0%-40.5%) for all 5 criteria. Conclusions and Relevance These 5 criteria have a high negative predictive value and the lowest false-negative rate, indicating they have the potential to allow for safe early discharge after laparoscopic colorectal surgery.

International audience; Background: The French Society of Surgery has endorsed a cohort aiming to prospectively assess the frequency of recurrence after incisional hernia repair and to identify the risk factors.Methods: Consecutive patients undergoing incisional hernia repair in the participating centers were included in the prospective French Society of Surgery cohort over a 6-month period. Patients were followed up with a computed tomography scan at 1 y and a clinical assessment by the surgeon at 2 years.Results: A total of 1,075 patients undergoing incisional hernia repair were included in 61 participating centers. The median follow-up was 24.0 months (interquartile range: 14.0-25.3). The follow-up rates were 83.0% and 68.5% at 1 and 2 years, respectively. The recurrence rates were 18.1% at 1 year and 27.7% at 2 years. Recurrence risk factors at 2 years were a history of hernia (odds ratio = 1.57, 95% confidence interval = 1.05-2.35, P = .028), a lateral hernia (odds ratio = 1.84, 95% confidence interval = 1.19-2.86, P = .007), a concomitant digestive operation (odds ratio = 1.97, 95% confidence interval = 1.20-3.22, P = .007), and the occurrence of early surgical site complications (odds ratio = 1,90, 95% confidence interval = 1.06-3.38, P = .030). The use of surgical mesh was strongly associated with a lower risk of recurrence at 2 years (P < .001).Conclusion: After incisional hernia repair, the 2-year recurrence rate is as high as 27.7%. History of hernia, lateral hernia, concomitant digestive operation, the onset of surgical site complications, and the absence of mesh are strong risk factors for recurrence.

IntroductionDespite 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 analysisThere 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 disseminationThe study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128).Trial registration numberCTRI/2020/09/027709; Pre-results.

Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive primary peritoneal neoplasia. At diagnosis, few patients are eligible for a recommended cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Among neoadjuvant strategies, pressurized intraperitoneal aerosol chemotherapy (PIPAC) combined with systemic chemotherapy has been recently proposed. This study evaluated this strategy in a cohort of DMPM patients.Patients with DMPM and primary or recurrent non-resectable diseases who received at least one PIPAC procedure in alternation with systemic chemotherapy were included in this retrospective study to analyze oncologic outcomes.Overall, 26 DMPM patients were treated with at least one PIPAC, including 20 patients with no previous CRS. Of 22 patients (85%) who had symptoms, 9 had perceptible ascites. Overall, 79 PIPAC procedures were performed, with half of the patients receiving three PIPAC procedures or more. Among eight patients (31%), 10 adverse events (13% of procedures) were reported, including two severe complications, both corresponding to digestive perforations. Improvement of symptoms was reported for 32% of the patients, whereas control of ascites was noted in 46%. All but one procedure among 14 patients (54%) secondarily treated by CRS-HIPEC were considered complete resections. After a median follow-up period of 29.6 months (95% confidence interval [CI], 17.6-not reached [NR]), the median overall survival period was 12 months (95% CI 11.1-NR). The median progression-free survival (PFS) was significantly better among the patients who underwent resection than among those who did not (33.5 vs 7.4 months; hazard ratio [HR], 0.18; 95% CI 0.06-0.755; p0.001).For patients with initially non-resectable DMPM, PIPAC is feasible for treatment with neoadjuvant intent and could facilitate complete secondary resection.

Background Well differentiated papillary peritoneal mesothelioma (WDPPM) is a rare variant of mesothelioma which affects mainly women in the reproductive age. The disease may present multifocally and recur after primary resection. Our aim was to describe the outcomes of cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this disease. Methods Patients with histological diagnosis of WDPPM were retrieved from the PSOGI registry. Demographical and clinical data were extracted as well as outcomes data (overall survival (OS) and recurrence free survival (RFS)). Results We analyzed 45 patients for whom complete data was available. The majority of patients were women (n = 33, 73%) with a median age of 44 years. Preoperative chemotherapy (CT) was administered in 8 patients (18%). Median peritoneal carcinomatosis index was 9 (1–30), and complete cytoreduction was achieved in 69% of patients. There was one case (2%) of postoperative mortality, and 24% rate of severe morbidity. Overall, there were 4 deaths and 5 years OS was 80%. 8 patients (18%) had disease recurrence, all within 5 years from operation. On univariate analysis preoperative CT, high PCI and severe morbidity were associated with reduced RFS. On multivariate analysis, only preoperative CT (HR = 32.6, 95% CI: 2.39–446.2, p = 0.009) and high PCI (HR = 21.7, 95% CI: 1.11–425.7, p = 0.04) remained significant risk factors. Conclusions WDPPM can be a lethal disease with substantial recurrence even after aggressive treatment. Patients presenting with extensive disease or disease recurrence after surgical excision are at increased risk for relapse. CRS + HIPEC can be safely applied to WDPPM in specialized centers.

International audience; BACKGROUND:The impact of the location of colorectal cancer on patient outcomes has been reported in several settings. The objective of this study was to assess the prognostic impact of the location of the primary colon cancer among patients with colorectal cancer peritoneal metastases undergoing complete cytoreductive surgery.METHODS:Using the prospectively maintained clinical and biological digestive peritoneal metastasis database of the BIG-RENAPE network, we identified 796 patients treated by a complete cytoreductive surgery between January 2004 and January 2017 for colorectal cancer peritoneal metastases in 16 different institutions. The 2 primary endpoints were overall survival and progression-free survival. To evaluate the impact on overall survival and progression-free survival of potential prognostic factors (including the location of the primary colorectal cancer), these factors were included in univariate and multivariate Cox proportional hazard models.RESULTS:Right-sided colorectal cancers were more often BRAF mutated and had microsatellite instability, whereas the frequency of RAS mutation was similar between right-sided and left-sided colorectal cancers. After a median follow-up time of 3.3 years, there was no significant difference in overall survival or progression-free survival according to tumor side. The lack of effect of tumor location on overall survival and progression-free survival was consistent across subgroups.CONCLUSION:Among patients undergoing complete cytoreductive surgery for peritoneal metastases, the site of the primary colorectal cancer was not associated with differences in progression-free survival or overall survival. Tumor side should not be used as a stratification factor in trials of colorectal cancer peritoneal metastases and should not be used in the selection process of patients for cytoreductive surgery.

Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare entity. Questions regarding management are still being debated as no more than 50 cases have been reported in the literature. We aimed to analyze the clinical, therapeutic, and prognostic data of patients with WDPMP from the RENAPE observational registry. All patients diagnosed with WDPMP and prospectively included in the RENAPE national registry between 2010 and 2018 were also included in our study. Expert pathologists from the RENA-PATH group confirmed all cases. All clinical, therapeutic, postoperative, and prognostic data were extracted and analyzed. We report on 56 patients with a mean age of 52 years (range 21–74). WDPMP was incidentally diagnosed during imaging or surgery in 16% and 36% of patients, respectively, and an association with synchronous malignancy was found in 18% of patients. Nine lesions showed discrete signs of fatty invasion. The median Peritoneal Cancer Index was 11 (range 0–33). Eleven patients were treated with definitive excision, 4 were treated with cytoreductive surgery (CRS) only, 37 were treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), and 2 were treated with CRS plus HIPEC plus early postoperative intraperitoneal chemotherapy. CRS was considered to be complete in 90% of cases. One patient died postoperatively and 16 patients (31%) faced postoperative complications. The median disease-free survival was 144 months; Four patients relapsed, with a median period of 27 months. No prognostic factors could be identified. Our analysis confirms the favorable prognosis of WDPMP. CRS and HIPEC could be a therapeutic option for diffuse, symptomatic, and/or recurrent disease.

Background: Complete cytoreduction is acknowledged to be an effective way to achieve macroscopic tumor clearance for a variety of tumors confined to the peritoneal cavity. Recent trials have shown that surgery respecting anatomical planes results in excellent outcomes and even the chance of cure for some from what was once thought to be life-limiting disease. Objective: To describe peritonectomy procedures in the current era. Method: A thorough and systematic method for cytoreductive surgery aimed at complete surgical resection of peritoneal metastases (PMs) was described. Results: The general principles of cytoreductive surgery were set out including preoperative preparation, patient positioning and incision. Strategies for assessing disease extent and planning surgical steps were outlined and established peritonectomy procedures such as Glisson's capsulectomy, omentectomy, left and right diaphragmatic peritonectomy, lesser omentectomy, stripping of the omental bursa, and pelvic peritonectomy were described. Novel techniques such as anterior pancreatic peritonectomy, small bowel mesenteric peritonectomy and cardiophrenic lymph node dissection were explained, and illustrated with accompanying video. Conclusion: Peritoneal metastases present a challenge to the surgeon which calls for a unique skill set if optimal outcomes are to be achieved. Attempts to standardize the surgical techniques described will allow further refinement as new technological advances occur.

Background: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice.Methods: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and country wide practice.Results: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies.Conclusion: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is increasingly used to treat patients with peritoneal cancer. A recent survey demonstrated considerable diversification of current practice of PIPAC raising issues of concern also regarding safety and efficacy. The study aim was to reach consensus on best practice of PIPAC treatment.METHODS: Current practice was critically discussed during an expert meeting and the available evidence was scrutinized to elaborate a 33-item closed-ended questionnaire. All active PIPAC centers were then invited to participate in an online two-round Delphi process with 3 reminders at least. Consensus was defined a priori as >70% agreement for a minimal response rate of 70%.RESULTS: Forty-nine out of 57 invited PIPAC centers participated in Delphi 1 and 2 (86%). Overall, there was agreement for 21/33 items. Consensus was reached for important aspects like advanced OR ventilation system (91.8%), remote monitoring (95.9%), use of the PRGS (85.7%) and use of a safety checklist (98%). The drug regimens oxaliplatin (87.8%) and cisplatin/doxorubicin (81.6%) were both confirmed by the expert panel. Important controversies included number and location of Biopsies during repeated PIPAC and the combination of PIPAC with additional surgical procedures.CONCLUSION: This consensus statement aims to allow for safe and efficacious PIPAC treatment and to facilitate multi-center analyses of the results. Additional preclinical and clinical studies are needed to resolve the remaining controversies.

Several studies have raised interest in the use of postoperative troponin levels to stratify risk of postoperative morbidity and mortality. In this study, postoperative troponin concentration after cytoreductive surgery (with or without hyperthermic intraoperative intraperitoneal chemotherapy) was associated with severe postoperative complications, and enhanced the predictive capability of a multivariable model focusing on postoperative complications.

Summary Background The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. Methods We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18–70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov , NCT00769405 , and is now completed. Findings Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0–77·1), median overall survival was 41·7 months (95% CI 36·2–53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1–49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63–1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). Interpretation Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. Funding Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

SCOPUS: ar.j, info:eu-repo/semantics/published