Background: the improved survival rates achieved using new polychemotherapy regimens in patients with metastatic pancreatic cancer (mPDAC) have suggested a potential role for surgery following a favorable response to initial chemotherapy (IC). The purpose of this systematic review is to summarize the available evidence on the role of surgery following IC in mPDAC, focusing on oligometastatic disease to the liver (lmPDAC). Methods: studies reporting on patients with lmPDAC undergoing surgery after IC were included. The main outcome was overall survival (OS). Results: six observational retrospective studies were included in the qualitative analysis. Data were retrieved on 2087 patients. The most common IC regimen in patients undergoing surgery was FOLFIRINOX (N 84, 73%). Only three studies reported survival comparison among patients treated with IC+surgery vs. IC alone. Median OS varied from 23 to 56 months after conversion surgery vs. 11 to 16.4 months after IC alone. Conclusions: despite wide heterogeneity of chemotherapy regimens, different downstaging criteria and potential selection biases, patients with oligometastatic lmPDAC undergoing surgery after IC have significantly higher survival rates compared to patients treated with IC alone. Future trials are needed for definition of univocal criteria of downstaging, oligometastatic definition and indications for surgery.

HIPEC is a potentially useful locoregional treatment combined with cytoreduction in patients with peritoneal colorectal metastases. Despite being widely used in several cancer centers around the world, its role had never been investigated before the results of three important RCTs appeared on this topic. The PRODIGE 7 trial clarified the role of oxaliplatin-based HIPEC in patients treated with radical surgery. Conversely, the PROPHYLOCHIP and the COLOPEC were designed to chair the role of HIPEC in patients at high risk of developing peritoneal metastases. Although all three trials demonstrated the relative ineffectiveness of HIPEC for treating or preventing peritoneal metastases, these results are not sufficient to abandon this technique. In addition to some criticisms relating to the design of the trials and their statistical value, the oxaliplatin-based HIPEC was found to be ineffective in preventing or treating peritoneal colorectal metastases, especially in patients already treated with systemic platinum-based chemotherapy. Several studies are ongoing investigating further HIPEC drugs and regimens. The review deeply discussed all the aspects and relapses of this new evidence.

Pseudomyxoma Peritonei (PMP) is an anatomo-clinical condition characterized by the implantation of neoplastic cells on peritoneal surfaces with the production of a large amount of mucin. The rarity of the disease precludes the evaluation of treatment strategies within randomized controlled trials. Cytoreductive Surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) has proven to be the only therapeutic option with potential chances of cure and long-term disease control. The present review discusses the epidemiology, pathogenesis, clinical presentation and treatment of PMP, focusing on the molecular factors involved in tumor progression and mucin production that could be used, in the upcoming future, to improve patient selection for surgery and to expand the therapeutic armamentarium.

Background: National guidelines (GLs) for surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of peritoneal malignancies (PMs) vary across countries, scientific societies, and government agencies. This study aimed to systematically review and compare the recommendations for CRS/HIPEC in the treatment of ovarian cancer (EOC), gastric cancer, colorectal cancer (CRC), mesothelioma, and pseudomyxoma peritonei (PMP). Methods: Medical databases, search engines, and national websites of 193 countries were queried using artificial intelligence (AI)-powered software for scientific societies and/or government agencies guidelines. The study excluded consensus statements and guidelines without appropriate references. Non-English guidelines were translated, and data, including GRADE strength of recommendations, were extracted. Results: The study analyzed 138 guidelines, 24 for gastric cancer, 36 for colorectal cancer, 29 for primary ovarian cancer (p-)EOC, 28 for recurrent ovarian cancer (r-)EOC, 10 for mesothelioma, and 11 for PMP. Guidelines were retrieved from 51 (26.4%) nations, mostly from developed countries (62.1%; p < 0.001). The CRS procedure received robust positive recommendations (GRADE I/IIa) for CRC (74.2%), p-/r-EOC (100%/78.5%), PMP (90.9%), and mesothelioma (90.0%). Conversely, CRS was not indicated for gastric cancer (61.6%, GRADE III; p < 0.001). The HIPEC procedure had robust positive recommendations for PMP (90.9%) and mesothelioma (90.0%), but was controversial for p-EOC (42.3%) and CRC (38.0%) and contraindicated for r-EOC (80.0%) and gastric cancer (62.4%) (p < 0.001). Conclusion: National guidelines concordantly recommend CRS for colorectal cancer, ovarian cancer, PMP, and mesothelioma. In contrast, HIPEC recommendations are less homogeneously shared, except for PMP and mesothelioma. No positive concordance exists among guidelines on gastric cancer for CRS nor HIPEC. Furthermore, high-level evidence is needed to strengthen future guidelines on peritoneal metastases.

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.

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y−OS CC−0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results.