Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.

Signet ring cell (SRC) colorectal cancer is strongly associated with peritoneal metastases (PM), but the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains uncertain due to poor prognosis. This study aimed to analyse the prognostic impact of SRCs, assess clinical characteristics, and evaluate the risk of open-close laparotomy. This Swedish population-based study included patients with colorectal PM accepted for initial CRS and HIPEC at four national centres between 2010 and 2023. Data were retrieved from the Swedish HIPEC registry. Tumours with ≥50 % and <50 % SRCs were included. Among 810 patients, 97 (12 %) had SRC tumours. SRC patients had a higher risk of open-close laparotomy (22 % vs. 13 %, p = 0.04) and worse 5-year overall survival (OS) compared to non-SRC patients (18 % vs. 32 %, p = 0.004). SRC patients were younger, more often had synchronous PM, regional lymph node metastases, higher peritoneal cancer index, and were less likely to receive neoadjuvant treatment or have synchronous liver metastases. At diagnosis, PM were more often an unexpected intraoperative finding, and SRC patients exhibited a stronger preoperative systemic inflammatory response, with a higher CRP/albumin ratio. Among those undergoing CRS and HIPEC, the 5-year OS was 24 % (95 % CI: 14-40) in SRC patients and 36 % (95 % CI: 32-42, p = 0.056) in non-SRC patients. SRC colorectal PM is associated with a high risk of open-close laparotomy, poor prognosis, and distinct clinical features. These findings highlight the aggressive nature of SRCs but suggest that CRS and HIPEC should not be excluded for these patients.

Background: Careful macroscopic assessment of surgical scars is needed to avoid routine scar resection during cytoreductive surgery (CRS) for peritoneal metastases (PM). This study aimed to analyze the correlation between macroscopically suspected and microscopically confirmed scar metastases (SMs), and to analyze the prognostic impact of not undergoing routine scar resection. Method: All patients with previous surgery, treated with CRS and hyperthermic intraperitoneal chemotherapy, for colorectal PM or pseudomyxoma peritonei (PMP), at Uppsala University Hospital in 2013–2021, were included. Macroscopic SMs in surgical reports were compared with histopathological analyses. Results: In total, 227 patients were included. Among colorectal PM patients (n = 156), SM was macroscopically suspected in 41 (26%) patients, and 63 (40%) underwent scar resection. SM was confirmed in 19 (30%). Among patients with macroscopic suspicion, 45% had confirmed SM (positive predictive value, PPV). A total of 1 of 23 (4%) patients with no macroscopic suspicion had SM (negative predictive value, NPV = 96%). Among the PMP patients (n = 71), SM was macroscopically suspected in 13 (18%), and 28 (39%) underwent scar resection, of whom 12 (43%) had SM. The PPV was 77%. Occult SM was found in 1 of 14 (NPV = 93%). Not undergoing routine scar resection did not affect recurrence-free survival (RFS, p = 0.2) or overall survival (OS, p = 0.1) in colorectal PM patients or PMP patients (RFS p = 0.7, OS p = 0.7). Conclusion: Occult SM is uncommon and scar resection does not affect RFS or OS. Therefore, macroscopically benign-appearing scars can be left without resection, though resection should be performed upon suspicion or uncertainty.

Aim: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for peritoneal metastases (PM) of colorectal or appendiceal origin. Rectal anastomotic leakage (RAL) or rectal stump blow‐out is a serious complication following rectal resection after CRS‐HIPEC. This study aimed to compare outcomes between ileo‐/colorectal anastomosis and rectal stump procedure and to identify risk factors for RAL and blow‐out. Method: Data were retrospectively collected between 2012 and 2024 from a prospectively maintained HIPEC Registry and supplemented with the review of medical records. Postoperative complications and the prevalence of RAL or blow‐out were registered. Pearson's chi‐squared test was used to compare differences in categorical variables. Logistic regression was used to identify risk factors for RAL and blow‐out. Results: Among 1271 CRS‐HIPEC procedures, 332 involved rectal resections. Patients received either an ileo‐/colorectal anastomosis ( n = 158) or had a rectal stump procedure ( n = 174). RAL occurred in 5.7% and blow‐out in 2.9% ( p = 0.201). In the rectal stump group, patients were older (65 vs. 59 years; p = 21 (OR 6.47; 95% CI: 0.84–50.1). Conclusion: Both reconstruction strategies following rectal resection in CRS‐HIPEC were associated with low rates of RAL or blow‐out. No independent risk factors were identified, indicating that the choice of surgical approach should be individualized based on clinical context rather than presumed leakage risk.

Background: National lead time goals have been implemented across Sweden to standardize and improve cancer patient care. However, the prognostic impact of lead times has not yet been studied in patients with colorectal cancer and peritoneal metastases scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Aim: To study the correlation between lead times and overall survival and operability. Methods: One hundred forty-eight patients with peritoneal metastases originating from colorectal cancer and scheduled for CRS + HIPEC from June 2012 to December 2019 were identified using a HIPEC register at Uppsala University Hospital. Data were collected from medical records concerning operability, overall survival, recurrence and time from diagnosis, and decision to operate to the date of surgery. Patients who had neoadjuvant therapy or no malignant cells in the resected specimens were excluded. Statistical calculations were made with the chi-squared test, Cox regression analysis, and log-rank test. Results: The median age was 66 years (27–82). Ninety-five were women and 53 were men. One hundred six underwent CRS + HIPEC, 13 CRS only, and 29 were inoperable (open-close). No difference in overall survival was seen when comparing patients with lead times ≤ 34 days and ≥ 35 days from the decision to operate at the multidisciplinary conference to the surgery but there was a higher frequency of open-close (p = 0.023) in the group with longer lead time. Factors that impacted overall survival were open-close (p < 0.001), liver metastases (p = 0.003), and peritoneal cancer index score ≥ 20 (p < 0.001). Conclusion: A long lead time from multidisciplinary conference to surgery has no direct impact on overall survival but can result in more cases of inoperability. In a larger cohort, this might translate into decreased survival, and efforts should therefore be made to complete preoperative work up as soon as possible and reduce overall time span. Important factors for survival are related to patient selection and extent of disease.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is standard treatment for peritoneal metastases in Sweden. Prolonged postoperative ileus (PPOI) is a common complication following major abdominal surgery and is associated with increased morbidity and prolonged hospitalization. The aim of this study was to evaluate the incidence of PPOI following CRS‐HIPEC and to identify factors associated with its development, including its relationship to postoperative complications. Methods: This retrospective, bicentre cohort study included patients undergoing CRS‐HIPEC for peritoneal metastases between January 2012 and 2024. Patients were identified through the Swedish HIPEC Registry, with supplementary data obtained from medical records. PPOI was defined as delayed defaecation beyond postoperative day 5 and/or prolonged use or reinsertion of a nasogastric tube. Clinical, surgical and postoperative outcomes were analysed and risk factors for PPOI were assessed using a multivariable logistic regression model. Results: A total of 982 patients were included, of whom 443 (45%) developed PPOI. Patients with PPOI had significantly longer hospital stays (median 11 vs. 9; p < 0.001) and delayed return of bowel function compared with patients without PPOI (median 6 vs. 3 days; p < 0.001). Major complications were more frequently observed in patients with PPOI (36% vs. 16%, p < 0.001). Independent risk factors for PPOI were major postoperative complications (aOR 3.74, CI 2.55–5.48), blood transfusion (aOR 1.70, CI 1.08–2.70) and omentectomy below the gastroepiploic arcade (aOR 1.51, CI 1.01–2.26). This association remained even after excluding patients with major postoperative surgical complications. Ileostomy formation was associated with a reduced risk of PPOI (aOR 0.51, CI 0.33–0.77). Conclusions: PPOI is a frequent complication following CRS‐HIPEC and is associated with increased postoperative morbidity and prolonged recovery. Strategies aimed to optimize perioperative care and enhanced recovery protocols may help to reduce the incidence and the adverse effects of PPOI.