The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers.

In today’s world, with its continuing advancements in genetics, the identification of Lynch syndrome (LS) increasingly relies on sophisticated genetic testing techniques. Most guidelines recommend a tailored surveillance program, as well as personalized prophylactic and therapeutic approaches, according to the type of dMMR gene mutation. Carriers of path_MLH1 and path_MSH2 genes have a higher risk of developing colorectal cancer (CRC), despite intensive colonoscopic surveillance. Conversely, carriers of path_MSH6 and path_PMS2 genes have a lower risk of developing CRC, which may be due to their lower penetrance and later age of onset. Thus, carriers of path_MLH1 or path_MSH2 would theoretically derive greater benefits from total colectomy, compared to low-risk carriers (path_MSH6 and path_PMS2), in which colonoscopic surveillance might achieve an efficient prophylaxis. Furthermore, regarding the risk of endometrial/ovarian cancer development, there is a global agreement to offer both hysterectomy and bilateral salpingo-oophorectomy to path_MLH1, path_MSH2 and path_MSH6 carriers after the age of 40. In patients with CRC, preoperative knowledge of the diagnosis of LS is of tremendous importance, due to the high risk of metachronous CRC. However, this risk depends on the type of dMMR gene mutation. For carriers of the high-risk variants (MLH1, MSH2 and EPCAM) who have already developed colon cancer, it is strongly recommended a subtotal or total colectomy is performed, while partial colectomy followed by endoscopic surveillance is an appropriate management approach to treat colon cancer in carriers of the low-risk variants (MSH6 and PMS2). On the other hand, extended surgery for index rectal cancer (such as total proctocolectomy) is less effective than extended surgery for index colon cancer from the point of view of metachronous CRC risk reduction, and is associated with a decreased quality of life.

Background/Objectives: In patients with peritoneal metastases from ovarian cancer, current clinical guidelines recommend “optimal cytoreductive surgery (CRS)”, defined as leaving no residual tumor nodules greater than 1 cm in diameter. Of note, the 1 cm threshold is somewhat arbitrary, as even a minimal residual tumor burden may adversely impact the patient’s outcomes. The aim of the current study is to identify the independent risk factors associated with overall survival (OS) and progression-free survival (PFS) after “optimal” CRS, with a special focus on the impact of completeness of cytoreduction (defined according to Sugarbaker’s scoring system). Methods: This retrospective cohort study included all the patients with peritoneal metastasis from ovarian cancer who underwent “optimal CRS” (residual nodules less than 1 cm), performed by a single team. Regarding the completeness of cytoreduction (CC), the patients were divided into two groups (without residual disease or with residual nodules less than 2.5 mm (CC0/CC1), and those with residual nodules larger than 2.5 mm and less than 1 cm (“optimal” CC2)). Risk factors associated with OS and PFS were identified by univariate and multivariate analysis. Results: Between September 2010 and February 2025, 52 patients with a median age of 62 [53.25–66.5] years underwent “optimal” CRS. For the entire group, the median OS was 70.83 months, and the median PFS was 25.8 months. In univariate analysis, the factors associated with significantly better OS were a peritoneal cancer index (PCI) lower or equal to 10 (vs. PCI > 10; p = 0.025) and CC0/CC1 status (vs. “optimal” CC2; p = 0.004), while in multivariate analysis, the only independent factor associated with higher OS was CC0/CC1 (HR = 0.253; 95% CI: 0.092–0.696, p = 0.008). Regarding PFS, the only factors independently associated with higher PFS were CC0/CC1 (HR = 0.155; 95% CI: 0.046–0.527, p = 0.003) and no preoperative chemotherapy (HR = 0.387; 95%CI: 0.155–0.963, p = 0.041). Conclusions: To the best of our knowledge, this is the first study to reveal that in patients with peritoneal metastases from ovarian carcinoma who underwent “optimal” CRS, the only independent factor associated with both better OS and PFS was the achievement of CC0/CC1 (no residual macroscopic nodules or residual nodules less than 2.5 mm). This observation supports the notion of redefining the threshold of “optimal” cytoreduction and potentially of implementing the Sugarbaker classification of cytoreduction even in ovarian cancer.