Gaia Colletti

Background/Objectives: OrganoHIPEC is a phase-II, two-stage, open-label clinical trial that investigates if cytoreductive surgery (CRS) and patient-tailored HIPEC, based on a preclinical platform using patient-derived organoids, can improve disease control in peritoneal metastases from colorectal cancer (CRC-PM). Methods: Adults with limited CRC-PM and no distant metastases were included. CRC-PM were sampled for organoid development during diagnostic laparoscopy. These organoids were used in an in vitro HIPEC model to test various drugs suitable for intraperitoneal administration. After 3–6 months of systemic chemotherapy, patients without progression underwent CRS/HIPEC with personalized regimens based on organoid drug response. To detect an increase in 12-month peritoneal disease-free survival from 40% to 60%, 24 patients are needed. According to the two-stage design, if n = 14), cisplatin/mitomycin-C (n = 12), and low-dose (120 min) oxaliplatin (n = 4). No patient was sensitive to high-dose oxaliplatin (30 min) and cisplatin/doxorubicin. Ten patients had a potential follow-up >12 months. Peritoneal relapse occurred at 8 months in two patients, and one died of liver metastases at 7 months. Seven patients remained PM-free for >12 months (median 16.4, range 12.6–28.4). Conclusions: A comprehensive precision approach using patient-derived organoids to guide personalized HIPEC is feasible and shows promising early results. High-dose oxaliplatin is poorly active. As 7/10 patients achieved the endpoint of 12-month PM-free survival, Stage-1 was successfully completed. The trial is proceeding to Stage-2.

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is an effective but potentially highly morbid treatment option for peritoneal surface malignancies. Adequate risk assessment is fundamental for clinical decision-making and informed patient consent. The aim of this study was to construct a validated nomogram predicting the risk of severe postoperative complications based exclusively on preoperative variables. Methods: A prospective database of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a single institution between February 1995 and April 2023 was reviewed. The cohort was divided randomly into derivation and validation cohorts (70 : 30). The primary outcome measure was postoperative complications (National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥ 3). Binary logistic regression identified preoperative variables significantly associated with postoperative morbidity. A nomogram was constructed based on the results of the multivariable analysis. The model’s performance was evaluated on the validation cohort by receiver operating characteristic curve analysis. Results: A total of 1039 patients were analysed. The majority of the patients were female (58.8%) and the median age was 56 (interquartile range 46–64) years. The postoperative complication rate was 37.7%, and the reoperation rate 12.7%. A nomogram was constructed based on the following predictive factors: age, body mass index, high-grade histology, disease identified in the left upper quadrant and surrounding the stomach and small bowel mesentery on preoperative imaging, preoperative white blood cell count, and Onodera nutritional index score. Receiver operating characteristic curve analysis showed an area under the curve of 0.707 with accurate calibration curves. Conclusion: Preoperative variables were selected and included in a simple nomogram predicting the risk of postoperative complications. This nomogram could aid clinicians in decision-making and patients in making informed decisions.

We carefully read the comment by Serrano et al.

Background: The balance between quality of life and colorectal cancer risk in familial adenomatous polyposis (FAP) patients is of primary importance. A cut-off of less than 30 polyps under 1 cm of diameter in the rectum has been used as an indication for performing ileo-rectal anastomosis (IRA) in terms of lower rectal cancer risk. This study aimed to assess clinical and surgical features of FAP patients who developed cancer of the rectal stump. Methods: This retrospective study included all FAP patients who underwent total colectomy/IRA from 1977 to 2021 and developed subsequent rectal cancer. Patients’ features were reported using descriptive statistics by considering the overall case series and within pre-specified classes of age (30 years) at first surgery. Results: Among the 715 FAP patients, 47 (6.57%, 95% confidence interval: 4.87; 8.65) developed cancer in the rectal stump during follow-up. In total, 57.45% of the population were male and 38.30% were proband. The median interval between surgery and the occurrence of rectal cancer was 13 years. This interval was wider in the youngest group (p-value: 0.012) than the oldest ones. Twelve patients (25.53%) received an endoscopic or minimally invasive resection. Amongst them, 61.70% were Dukes stage A cancers. Conclusions: There is a definite risk of rectal cancer after total colectomy/IRA; however, the time interval from the index procedure to cancer developing is long. Minimally invasive and endoscopic treatments should be the procedures of choice in patients with early stage cancers.