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. Full article

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. Full article

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may significantly improve survival for selected patients with peritoneal surface malignancies, but it has always been criticized due to the high incidence of postoperative morbidity and mortality. Methods: Data were collected from nine Italian centers with peritoneal surface malignancies expertise within a collaborative group of the Italian Society of Surgical Oncology. Complications and mortality rates were recorded, and multivariate Cox analysis was used to identify risk factors. Results: The study included 2576 patients. The procedure was mostly performed for ovarian (27.4%) and colon cancer (22.4%). The median peritoneal cancer index was 13. Overall postoperative morbidity and mortality rates were 34% and 1.6%. A total of 232 (9%) patients required surgical reoperation. Multivariate regression logistic analysis identified the type of perfusion (p ≤ 0.0001), body mass index (p ≤ 0.0001), number of resections (p ≤ 0.0001) and colorectal resections (p ≤ 0.0001) as the strongest predictors of complications, whereas the number of resections (p ≤ 0.0001) and age (p = 0.01) were the strongest predictors of mortality. Conclusions: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a valuable option of treatment for selected patients with peritoneal carcinomatosis providing low postoperative morbidity and mortality rates, if performed in high-volume specialized centers. Full article

Gastric cancer (GC) continues to be one of the leading types of malignancies worldwide, despite an ongoing decrease in incidence. It is the fifth most frequent type of cancer in the world and the fourth leading cause of cancer death. Peritoneal metastases (PMs) occur in 20–30% of cases during the natural history of the disease. Systemic chemotherapy (SC) is undoubtedly the standard of care for patients with GC and PMs. However, with the development of highly effective regimens (SC combined with intraperitoneal chemotherapy), significant tumor shrinkage has been observed in many patients with synchronous GC and PMs, allowing some to undergo curative resection “conversion surgery” with long-term survival. In recent years, there has been growing interest in intraperitoneal chemotherapy for PMs, because the reduced drug clearance associated with the peritoneal/plasma barrier allows for direct and prolonged drug exposure with less systemic toxicity. These procedures, along with other methods used for peritoneal surface malignancies (PSMs), can be used in GCs with PMs as neoadjuvant chemotherapy or adjuvant treatments after radical surgery or as palliative treatments delivered either laparoscopically or—more recently—as pressurized intraperitoneal aerosol chemotherapy. The great heterogeneity of patients with stage IV gastric cancer did not allow us to carry out a systemic review; therefore, we limited ourselves to providing readers with an overview to clarify the indications and outcomes of integrated treatments for GCs with PMs by analyzing reports from the international clinical literature and the specific experiences of our oncoteam. Full article

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. Full article

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare form of mesothelioma that carries a very poor prognosis. The 5-year overall survival is about 20% (±5.9). Survival is optimal for patients suitable for cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC), with a median OS ranging from 34 to 92 months. However, selecting patients for surgery remains a complex task and requires a careful preoperative workup, rational analysis of prognostic profiles, and risk prediction models. Systemic chemotherapy could be offered: (1) in the adjuvant setting for high-risk patients; (2) for patients not eligible for CRS; and (3) for those with recurrent disease. It mainly includes the combination of Platin compound with Pemetrexed or immunotherapy. The biology of DMPM is still largely unknown. However, progress has been made on some fronts, such as telomere maintenance mechanisms, deregulation of apoptosis, tyrosine kinase pathways, and mutation of BRCA1-associated protein 1 (BAP1). Future perspectives should include translational research to improve our understanding of the disease biology to identify druggable targets. We should also clear the role of immune checkpoint inhibitors and investigate new locoregional technologies, such as pressurized intraperitoneal aerosol chemotherapy (PIPAC) or normothermic intraperitoneal chemotherapy (NIPEC). Full article

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. Full article

Ovarian cancer is the eighth most common neoplasm in women with a high mortality rate mainly due to a marked propensity for peritoneal spread directly at diagnosis, as well as tumor recurrence after radical surgical treatment. Treatments for peritoneal metastases have to be designed from a patient’s perspective and focus on meaningful measures of benefit. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with regional chemotherapy, has been proposed to treat advanced ovarian cancer. Preliminary results to date have shown promising results, with improved survival outcomes and tumor regression. As knowledge about the disease process increases, practice guidelines will continue to evolve. In this review, we have reported a broad overview of advanced ovarian cancer management, and an update of the current evidence. The future perspectives of the Italian Society of Surgical Oncology (SICO) are discussed conclusively. Full article

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. Full article

Over two thirds of ovarian cancer patients present with advanced stage disease at the time of diagnosis. In this scenario, standard treatment includes a combination of cytoreductive surgery and carboplatinum–paclitaxel-based chemotherapy. Despite the survival advantage of patients treated with upfront cytoreductive surgery compared to women undergoing neo-adjuvant chemotherapy (NACT) and interval debulking surgery (IDS) due to high tumor load or poor performance status has been demonstrated by multiple studies, this topic is still a matter of debate. As a consequence, selecting the adequate treatment through an appropriate diagnostic pathway represents a crucial step. Aiming to assess the likelihood of leaving no residual disease at the end of surgery, the role of the CT scan as a predictor of cytoreductive outcomes has shown controversial results. Similarly, CA 125 level as an expression of tumor load demonstrated limited applicability. On the contrary, laparoscopic assessment of disease distribution through a validated scoring system was able to identify, with the highest specificity, patients undergoing suboptimal cytoreduction and therefore best suitable for NACT-IDS. Against this background, with this article, we aim to provide a comprehensive review of available evidence on the diagnostic and treatment pathways of advanced ovarian cancer. Full article

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. Full article