Background: Since 2011, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has emerged as a promising treatment option for patients with peritoneal surface malignancies (PSM) who are not eligible for cytoreductive surgery (CRS). Repeated minimal-invasive treatment is one of the key features and the current empirical standard treatment (ST) consists of at least three administrations over about three months. However, many patients are unable to complete the full course, limiting the potential benefits of PIPAC. Method: This retrospective, single-center study assessed the completion rate of ST and identified the main causes and predictive factors for discontinuation. This study also evaluated the feasibility, safety, and efficacy of PIPAC and investigated whether improved patient selection over the years has resulted in better oncological outcomes. Result: Data from 168 patients treated with PIPAC between January 2017 and March 2023 for a total of 336 procedures showed that only 29% completed ST. Multivariate analysis identified ascites >500 mL and a prior history of bowel obstruction as significant predictors of discontinuation. Conclusions: Patients with radiological or clinical signs of obstruction should not be considered for PIPAC treatment, and ascites increases the risk of incomplete treatment. Larger studies are eagerly awaited to corroborate these findings and refine the selection criteria by disease entity.

IntroductionGastric cancer (GC) is the fourth leading cause of cancer-related death worldwide with limited therapeutic options. The aim of this study was to analyze the value of adding surgery to the first-line treatment in patients with oligometastatic GC (OGC).MethodsThis retrospective study included patients with OGC who underwent induction chemotherapy followed by surgery of both primary tumor and synchronous metastasis between April 2012 and April 2022. Endpoints were overall survival (OS) and relapse-free survival (RFS) analyzed by the Kaplan–Meier method. Prognostic factors were assessed with the Cox model.ResultsData from 39 patients were collected. All cases were referred to our multidisciplinary tumor board (MTB) to evaluate the feasibility of radical surgery. After a median follow-up of 33.6 months (mo.), median OS was 26.6 mo. (95% CI 23.8–29.4) and median RFS was 10.6 mo. (95% CI 6.3–14.8). Pathologic response according to the Mandard criteria (TRG 1–3, not reached versus 20.5 mo. for TRG 4–5; HR 0.23, p=0.019), PS ECOG ≤ 1 (26.7 mo. for PS ≤ 1 versus 11.2 mo. for PS >1; HR 0.3, p=0.022) and a low metastatic burden (26.7 mo. for single site versus 12.9 mo. for ≥2 sites; HR 0.34, p=0.039) were related to good prognosis. No major intraoperative complications nor surgery-related deaths occurred in our series.DiscussionA sequential strategy of preoperative chemotherapy and radical surgical excision of both primary tumor and metastases was demonstrated to significantly improve OS and RFS. Multidisciplinary evaluation is mandatory to identify patients who could benefit from this strategy.

BACKGROUND:Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies. METHODS:A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation. RESULTS:All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges. CONCLUSIONS:The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care.

Background: Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. Methods: A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. Results: Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8–28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9–8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (−1.8954 (95% CI: −2.5761 to −1.2146; p < 0.001). Conclusions: CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC.

BackgroundThere is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.Materials and methodsData were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)].ResultsKRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001).ConclusionsIn patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Background: Advances in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have improved outcomes for selected patients with peritoneal surface malignancies (PSMs). Methods: This retrospective study analyzed 743 PSM patients treated at Fondazione Policlinico Universitario Agostino Gemelli from January 2016 to February 2024. The primary aim was to assess median overall survival (mOS), median disease-free survival (mDFS), and median progression-free survival (mPFS) stratified by tumor origin. Secondary outcomes examined the role of diagnostic laparoscopy in the management of PSMs and intra- and postoperative complications’ rates. Results: A total of 1113 procedures were performed: 389 CRS, 370 PIPAC, and 354 diagnostic laparoscopies. Colorectal cancer was the predominant indication for CRS (52.4%), with a mOS of 52 months and mDFS of 22 months. Patients affected by gastric cancer undergoing CRS had a mOS of 18 months and a mDFS of 13 months, while PIPAC yielded a mOS of 9 months and a mPFS of 4 months. Among patients with pseudomyxoma peritonei undergoing CRS, the 5-year DFS rate was 64.1%, and OS rate was 89%. Patients affected by mesothelioma and treated with CRS exhibited a median OS of 43 months and a DFS of 26 months. Pancreatic and hepatobiliary cancers were treated with PIPAC, with a respective mOS of 12 and 8 months. Postoperative complications occurred in 12.6% of CRS, 3.2% of PIPAC, and 1.7% of diagnostic laparoscopies. High peritoneal cancer index (PCI), gastric resection, and blood loss over 500 mL were identified as risk factors for major complications in a multivariate analysis. Conclusions: Developing a highly experienced multidisciplinary team is crucial for delivering tailored treatment strategies which aim to achieve optimal oncological outcomes while preserving patients’ quality of life.

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

Objectives Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM.Methods The Nab-PIPAC trial is a single-center, prospective, open-label, phase II study (ClinicalTrials.gov identifier: NCT05371223). Its primary goal is to evaluate the antitumor activity of the combined treatment based on Disease Control Rate (DCR) using RECISTv.1.1 criteria. Secondary objectives include feasibility, safety, pathological response, progression-free and overall survival, nutritional status, quality of life, pharmacokinetics of NabPaclitaxel-PIPAC, and PM molecular evolution via translational research. The treatment protocol consists of three courses, each with two cycles of intravenous NabPaclitaxel-Gemcitabine and one cycle of NabPaclitaxel-PIPAC, with standard metastatic pancreatic cancer doses for the former and 112.5 mg/m2 for the latter. Sample size follows Simon's two-stage design: 12 patients in stage one and 26 in stage two (80 % power, 0.1 alpha).Results Partial results will be available after first stage enrollment.Conclusions This trial aims to determine the antitumor efficacy and safety of combining NabPaclitaxel-PIPAC with systemic NabPaclitaxel-Gemcitabine in pancreatic cancer patients with PM.

Gastric cancer with peritoneal metastasis (GCPM) has an unfavourable prognosis. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are promising treatment options that have been shown to improve survival. The aim of this study was to assess the impact of different treatments such as systemic chemotherapy, systemic chemotherapy + PIPAC, and CRS + HIPEC in patients with GCPM. This single-centre retrospective study included 82 patients with GCPM treated between January 2016 and June 2021. After first-line chemotherapy, depending on disease response and burden, the patients were divided into three treatment groups: chemotherapy alone, chemotherapy + PIPAC, and CRS + HIPEC. The primary outcome was overall survival (OS) from diagnosis, which was compared among the treatment groups. Thirty-seven (45.1

Introduction: The selection of patients undergoing cytoreductive-surgery (CRS) followed by hyper -thermic intraperitoneal chemotherapy (HIPEC) is crucial. BIOSCOPE and COMPASS are prognostic scores designed to stratify survival into four classes according to clinical and pathological features. The purpose of this study is to analyze the prognostic role of these scores using a large cohort of patients as an external reference.Methods: Overall survival analysis was performed using Log-Rank and Kaplan-Meier curves for each score. The probability of survival at 12, 36, and 60 months was tested using receiver operating charac-teristic (ROC) curves to determine sensitivity and specificity.Results: From the validation cohort of 437 patients, the analysis included 410 patients in the COMPASS group and 364 patients in the BIOSCOPE group (100% data completeness). We observed a different pa-tient distribution between classes (high-risk for BIOSCOPE compared to COMPASS, p = 0.0001). Never-theless, both COMPASS and BIOSCOPE effectively stratified overall survival (Log-Rank, p = 0.0001 in both cases), with a lack of discrimination between COMPASS classes II and III (p = n.s.). COMPASS at 12 m and BIOSCOPE at 60 m showed the best performance in terms of survival prediction (AUC of 0.82 and 0.81). The specificity of the two tests is good (median 81.3%), whereas sensibility is quite low (median 64.2%).Conclusion: Following external validation in a large population of patients with CRC-PM who are eligible for surgery, the COMPASS and BIOSCOPE scores exhibit high inter-test variability but effectively stratify cancer-related mortality risk. While the quality of the scores is similar, BIOSCOPE shows better inter-tier

Aim: Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. Method: The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. Results: A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Conclusion: Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients.

Enhanced recovery after surgery (ERAS) program refers to a multimodal intervention to reduce the length of stay and postoperative complications; it has been effective in different kinds of major surgery including colorectal, gynaecologic and gastric cancer surgery. Its impact in terms of safety and efficacy in the treatment of peritoneal surface malignancies is still unclear. A systematic review and a meta-analysis were conducted to evaluate the effect of ERAS after cytoreductive surgery with or without HIPEC for peritoneal metastases. MEDLINE, PubMed, EMBASE, Google Scholar and Cochrane Database were searched from January 2010 and December 2021. Single and double-cohort studies about ERAS application in the treatment of peritoneal cancer were considered. Outcomes included the postoperative length of stay (LOS), postoperative morbidity and mortality rates and the early readmission rate. Twenty-four studies involving 5131 patients were considered, 7 about ERAS in cytoreductive surgery (CRS) + HIPEC and 17 about cytoreductive alone; the case histories of two Italian referral centers in the management of peritoneal cancer were included. ERAS adoption reduced the LOS (−3.17, 95% CrI −4.68 to −1.69 in CRS + HIPEC and −1.65, 95% CrI −2.32 to –1.06 in CRS alone in the meta-analysis including 6 and 17 studies respectively. Non negligible lower postoperative morbidity was also in the meta-analysis including the case histories of two Italian referral centers. Implementation of an ERAS protocol may reduce LOS, postoperative complications after CRS with or without HIPEC compared to conventional recovery.

Malignant mesothelioma is a rare aggressive tumour of the mesothelium with a propensity to spread locally and, rarely, to distant organs. The latest advances in its diagnosis and treatment have led to an increase in unusual disease presentations. Although a direct invasion of the perineum has been previously described in a men, a malignant mesothelioma spreading to the perianal region was never reported in a women. We presented a rare case of malignant mesothelioma recurrence spreading from the peritoneal cavity to the perineum through the rectovaginal space.

Introduction:Ovarian cancer (OC) is the primary cause of mortality in women diagnosed with gynecological cancer. Our study assessed pressurized intraperitoneal aerosol chemotherapy (PIPAC) as treatment for peritoneal surface metastases (PSM) from recurrent or progressive OC and conducted survival analyses to identify prognostic factors.Material and methods:This retrospective cohort study, conducted across 18 international centers, analyzed the clinical practices of patients receiving palliative treatment for PSM from OC who underwent PIPAC. All patients were initially treated appropriately outside any clinical trial setting. Feasibility, safety, and morbidity were evaluated along with objective endpoints of oncological response. Multivariate analysis identified prognostic factors for OS and PFS.Results:From 2015-2020, 234 consecutive patients were studied, from which 192 patients were included and stratified by platinum sensitivity for analysis. Patients with early recurrence, within one postoperative month, were excluded. Baseline characteristics were similar between the groups regarding platinum sensitivity (platinum sensitive (PS) and resistant (PR)), but chemotherapy frequency differed, as did PCI before PIPAC. Median PCI decreased in both groups after three cycles of PIPAC (PS 16 vs. 12, p < 0.001; PR 24 vs. 20, p = 0.009). Overall morbidity was 22%, with few severe complications (4-8%) or mortality (0-3%). Higher pathological response and longer OS (22 vs. 11m, p = 0.012) and PFS (12 vs. 7m, p = 0.033) were observed in the PS group. Multivariate analysis (OS/PFS) identified ascites (HR 4.02, p < 0.001/5.22, p < 0.001), positive cytology at first PIPAC (HR 3.91, p = 0.002/1.96, p = 0.035), and ≥ 3 PIPACs (HR 0.30, p = 0.002/0.48, p = 0.017) as independent prognostic factors of overall survival/progression-free survival.Conclusions:With low morbidity and mortality rates, PIPAC is a safe option for palliative treatment of advanced ovarian cancer. Promising results were observed after 3 PIPAC, which did improve the peritoneal burden. However, further research is needed to evaluate the potential role of PIPAC as an independent prognostic factor.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance in clinical practice. Performing CRS and HIPEC laparoscopically represents a challenging and intriguing technical evolution. However, the experiences are limited, and the evidence is low. This retrospective analysis was performed on patients treated with laparoscopic CRS-HIPEC within the Italian Peritoneal Surface Malignancies Oncoteam. Clinical, perioperative, and follow-up data were extracted and collected on prospectively maintained databases. We added a systematic review according to the PRISMA method for English-language articles through April 2022 using the keywords laparoscopic, hyperthermic, HIPEC, and chemotherapy. From 2016 to 2022, fourteen patients were treated with Lap-CRS-HIPEC with curative intent within the Italian centers. No conversion to open was observed. The median duration of surgery was 487.5 min. The median Peritoneal Cancer Index (PCI) was 3, and complete cytoreduction was achieved in all patients. Two patients (14.3%) had major postoperative complications, one requiring reintervention. After a median follow-up of 16.9 months, eleven patients were alive without disease (78.6%), two patients developed recurrence (14.3%), and one patient died for unrelated causes (7.1%). The literature review confirmed these results. In conclusion, current evidence shows that Lap-CRS-HIPEC is feasible, safe, and associated with a favorable outcome in selected patients. An accurate patient selection will continue to be paramount in choosing this treatment.

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 (I2 28.41%, p = 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.

Background We aimed to investigate the therapeutic efficacy and safety of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in platinum-resistant recurrence of ovarian cancer and peritoneal carcinomatosis, while our secondary endpoint was to establish any changes in quality of life estimated via the EORTC QLQ-30 and QLQ-OV28 questionnaires. Methods In this monocentric, single-arm, phase II trial, women were prospectively recruited and every 28–42 days underwent courses of PIPAC with doxorubicin 2.1 mg/m 2 followed by cisplatin 10.5 mg/m 2 via sequential laparoscopy. Results Overall, 98 PIPAC procedures were performed on 43 women from January 2016 to January 2020; three procedures were aborted due to extensive intra-abdominal adhesions. The clinical benefit rate (CBR) was reached in 82% of women. Three cycles of PIPAC were completed in 18 women (45%), and 13 (32.5%) and 9 (22.5%) patients were subjected to one and two cycles, respectively. During two PIPAC procedures, patients experienced an intraoperative intestinal perforation. There were no treatment-related deaths. Nineteen patients showed no response according to the Peritoneal Regression Grading Score (PRGS) and 8 patients showed minor response according to the PRGS. Median time from ovarian cancer relapse to disease progression was 12 months (95% confidence interval [CI] 6.483–17.517), while the median overall survival was 27 months (95% CI 20.337–33.663). The EORTC QLQ-28 and EORTC QLQ-30 scores did not worsen during therapy. Conclusions PIPAC seems a feasible approach for the treatment of this subset of patients, without any impact on their quality of life. Since this study had a small sample size and a single-center design, future research is mandatory, such as its application in addition to systemic chemotherapy.

Objectives Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug administration method with promising efficacy for the treatment of peritoneal metastases (PM). This study aimed to evaluate the prognostic value of an immunonutritional assessment on the feasibility, safety, and survival in this setting. Methods Data of PM patients undergoing PIPAC between September 2018 and May 2020 were prospectively recorded. A CT scan-derived body composition assessment was performed for each patient. Results Fifty-one patients were enrolled, of which 30 (58%) underwent multiple PIPAC cycles, with a pathological response rate of 55%. Prognostic nutritional index (PNI) and neutrophil-to-lymphocytes predicted completion of more than one PIPAC cycle, with a cut off of 36.5 and 4.8 respectively. Muscle attenuation and body fat tissues were associated with pathological response. At multivariate Cox regression analysis, only the presence of a low PNI (HR 2.41, 95% CI 1.08-5.46) was significantly associated with a worse OS. Conclusions A pretreatment immunonutritional assessment may provide valuable information for PIPAC patients' selection and survival, while body composition parameters are able to predict pathological response. Further larger studies are needed to validate the role of these biomarkers in tailoring the treatment and monitoring PM patients undergoing PIPAC.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.