BACKGROUND: To improve care for patients with colorectal peritoneal metastases (CRC-PM) or pseudomyxoma peritonei (PMP), the Dutch CRS-HIPEC quality registry was initiated in 2019. The aims are to describe the development and content of this registry and to give insight into the data collected during the first years.
METHODS: The registry is an observational cohort in the Netherlands. All patients with CRC-PM or PMP who intend to undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) from 6 hospitals are included. Clinical data and outcomes (including hospital variation) were analyzed.
RESULTS: In 2019-2022, 889 patients were included in the CRS-HIPEC quality registry: 749 (84 %) with CRC-PM and 140 (16 %) with PMP. Peritoneal metastases were diagnosed synchronously in 51 % of CRC-PM patients and in 94 % of PMP patients. In patients undergoing complete CRS, the median peritoneal cancer index was 8 (IQR 4-13) for CRC-PM and 15 (IQR 6-26) for PMP. Complete cytoreduction was achieved in 639 CRC-PM patients (97 %) and 108 PMP patients (82 %). HIPEC was mainly performed with mitomycin C (CRC-PM: 94 %, PMP: 92 %). Major postoperative complications (Clavien-Dindo grade ≥3) occurred in 148 CRC-PM patients (22 %) and 30 PMP patients (23 %) with 90-day mortality rates of 2 %. In CRC-PM, differences between hospitals were observed regarding proportions of diagnostic laparoscopies/laparotomies, (neo)adjuvant treatment, ostomy formations and re-admissions.
CONCLUSIONS: The CRS-HIPEC quality registry provides insight into the outcomes of CRS-HIPEC and enables clinical auditing and observational cohort studies aiming to improve treatment outcomes for patients with CRC-PM and PMP.

BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined.
OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population.
METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics.
RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05).
CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to reduce length of stay (LOS) and complications. The impact of ERAS protocols on the cost of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has not been studied.
METHODS: We performed a retrospective cohort analysis of patients undergoing CRS-HIPEC from 2016-2022 at a single quaternary center. Propensity score matching was used to create pre-and post-ERAS cohorts. Cost, overall and serious complications, and intensive care unit (ICU) length of stay (LOS) between the two cohorts were compared using the Mann-Whitney U-test for continuous variables and χ2 test for categorical variables.
RESULTS: Our final matched cohort consisted of 100 patients, with 50 patients in both the pre- and post-ERAS groups. After adjusting for patient complexity and inflation, the median total cost [$75,932 ($67,166-102,645) versus $92,992 ($80,720-116,710), p = 0.02] and operating room cost [$26,817 ($23,378-33,121) versus $34,434 ($28,085-$41,379), p < 0.001] were significantly higher in the post-ERAS cohort. Overall morbidity (n = 22, 44% versus n = 17, 34%, p = 0.40) and ICU length of stay [2 days (IQR 1-3) versus 2 days (IQR 1-4), p = 0.70] were similar between the two cohorts. A total cost increase of $22,393 [SE $13,047, 95% CI (-$3178 to $47,965), p = 0.086] was estimated after implementation of ERAS, with operating room cost significantly contributing to this increase [$8419, SE $1628, 95% CI ($5228-11,609), p < 0.001].
CONCLUSIONS: CRS-HIPEC ERAS protocols were associated with higher total costs due to increased operating room costs at a single institution. There was no significant difference in ICU LOS and complications after the implementation of the ERAS protocol.

OBJECTIVE: Patients with colorectal peritoneal metastases (PM) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are at high risk of recurrent disease. Understanding where and why recurrences occur is the first step in finding solutions to reduce recurrence rates. Although diffusion-weighted (DW) MRI is not routinely used in the follow-up of CRC patients, it has a clear advantage over CT in detecting the location and spread of (recurrent) PM. This study aimed to identify common locations of recurrence in CRC patients after CRS-HIPEC with MRI.
METHODS: This was a single-centre retrospective study of patients with recurrent PM after CRS-HIPEC performed between January 2016 and August 2020. Patients were eligible for inclusion if they had both an MRI preoperatively (MRI1) and at the time of recurrent disease (MRI2). Two abdominal radiologists reviewed in consensus and categorized recurrences according to their location on MRI2 and in correlation with previous disease location on prior imaging (MRI1) and the surgical report of the CRS-HIPEC.
RESULTS: Thirty patients were included, with a median surgical PCI of 7 (range 3-21) at the time of primary CRS-HIPEC. In total, 68 recurrent metastases were detected on MRI2, of which 14 were extra-peritoneal. Of the remaining 54 PM, 42 (78%) occurred where the peritoneum was damaged due to earlier resections or other surgical procedures (e.g. inserted surgical abdominal drains). Most recurrent metastases were found in the mesentery, lower abdomen/pelvis and abdominal wall (87%).
CONCLUSIONS: Most recurrent PMs appeared in the mesentery, lower abdomen/pelvis and abdominal wall, especially where the peritoneum was previously damaged.

The incidence of incisional hernias (IH) after midline laparotomy varies from 11% to 20%. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is potentially prone to hernias because a Xiphoid to pubis laparotomy incision performed on patients who have undergone previous abdominal surgeries with the addition of chemotherapy and its related adverse effects.
We performed a retrospective analysis on a prospectively maintained single institution database from March 2015 to July 2020. The inclusion criteria were patients who underwent CRS-HIPEC and had at least 6 months postoperative follow-up with post-operative cross-sectional imaging study.
Two hundred and one patients were included in the study. All patients underwent CRS-HIPEC with resection of previous scar and umbilectomy. Fifty-four patients were diagnosed with IH (26.9%). The major risk factors for IH in multivariate analysis were higher American society of Anesthesiologists score (ASA) (OR 3.9, P = 0.012), increasing age (OR 1.06, P = 0.004) and increasing BMI (OR 1.1, P = 0.006). Most of the hernia sites were median (n = 43, 79.6%). Eleven (20.4%) patients had lateral hernias due to stoma incisions or drain sites. Most of the median hernias were at the level of the resected umbilicus 58.9% (n = 23). Five (9.3%) of the patients with IH necessitated an urgent surgical repair.
We have demonstrated that more than a quarter of the patients after CRS-HIPEC suffer from IH and up to 10% of them may require surgical intervention. More research is needed to find the appropriate intraoperative interventions to minimize this sequela.

Purpose: To assess the safety and long-term outcome of a multimodality treatment consisting of radical surgery, intra-operative radiotherapy (IORT), and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with locally advanced rectal cancer (LARC) or locally recurrent rectal carcinoma (LRRC) and peritoneal metastases (PM). Methods: The present study was a single-center cohort study, including all consecutive patients undergoing this treatment in a tertiary referral center for LARC, LRRC, and PM. Postoperative complications, intensive care stay (ICU stay), and re-admission rates were assessed as well as disease-free survival (DFS) and overall survival (OS). Results: A total of 14 LARC and 16 LRRC patients with PM were included in the study. The median ICU stay was 1 day, and 57% of patients developed a severe postoperative complication. No 90-day mortality was observed. Median DFS was 10.0 months (Interquartile Range 7.1-38.7), and median OS was 31.0 months (Interquartile Range 15.9-144.3). Conclusions: As postoperative complications and survival were in line with treatments that are accepted for LARC or LRRC and PM as separate procedures, we conclude that combined treatment with IORT and CRS-HIPEC should be considered as a treatment option for selected patients with LARC or LRRC and peritoneal metastases in tertiary referral centers.

Purpose-To compare patient-reported outcomes (PROs) of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for colorectal peritoneal metastases to PROs of colorectal cancer (CRC) patients undergoing conventional surgery. Methods-Data were extracted from the CAIRO6 trial (CRS-HIPEC group) and the PROCORE study (conventional surgery group). Nine predefined PROs (derived from the EORTC QLQ-C30 questionnaire) were compared at baseline, in the early postoperative period and one year postoperatively, with correction for treatment with systemic therapy using linear mixed modeling. Results-In total, 331 patients were included: 71 in the CRS-HIPEC group and 260 in the conventional surgery group. All predefined PROs (fatigue, diarrhea, C30 summary score, Global Health Status, physical, role, emotional, cognitive, and social functioning) did not differ significantly between the groups at all three timepoints, and differential effects over time for all PROs did not differ significantly between the groups. Significant worsening of fatigue, C30 summary score, physical and role functioning (both groups), and cognitive and social functioning (conventional surgery group only) was present in the early postoperative period. All scores returned to baseline at one year postoperatively, except for physical and cognitive functioning in the conventional surgery group. Emotional functioning improved postoperatively in both groups compared to baseline. Conclusion-Despite a more extensive procedure with greater risk of morbidity, CRS-HIPEC in patients with colorectal peritoneal metastases did not have a greater negative impact on PROs than conventional surgery in patients with CRC. Further, systemic therapy did not affect these PROs. These findings may facilitate future patient counseling and shared decision making in clinical practice.

BACKGROUND: The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).
METHODS: We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the \"sandwich\" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy.
RESULTS: A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS.
CONCLUSIONS: In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.

BACKGROUND: Pseudomyxoma peritonei (PMP) is an uncommon clinical condition characterized by the presence of mucinous ascites, mainly induced by perforated appendiceal mucinous neoplasms (AMN). The peritoneal surface of the small bowel is usually spared from disease manifestation due to peristaltic movements. Mucinous tumours can disseminate as PMP on the entire peritoneum, but are rarely intraluminal. For the first time in literature, we report a case of intraluminal PMP involving the ileum.
METHODS: A 75-year-old male was treated for perforated AMN and disseminated PMP with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. During follow-up, the patient developed intraperitoneal recurrence together with intraluminal depositions in the ileum, both disease manifestations with identical KRAS and SMAD4 mutations. Hereafter, the patient was treated with palliative care.
CONCLUSIONS: This case illustrates the variation in the biological and clinical behaviour of this rare disease. Clinicians should be aware of unusual tumour distribution patterns of PMP, including the presence of mucinous tumour within the small bowel.

Frequency of PD-L1 expression and the role of immunotherapy in malignant peritoneal mesothelioma (MPM) have not been well characterized. The purpose of this study was to determine PD-L1 expression in patients with MPM and perform an exploratory analysis for associations between PD-L1 and its biological behavior in MPM.
Tumor samples were collected from patients undergoing surgical interventions between January 2018 and June 2020. Specimens were stained with anti-PD-L1 antibodies (Dako 22c3) and positivity was determined by tumor proportion score (TPS) or combined positive score (CPS) being ≥1%.
Twenty one samples were obtained from 21 patients. Sixteen of 21 (76%) samples were CPS positive and 9 of 21 (43%) were TPS positive. Three samples had more aggressive biphasic/sarcomatoid histology and a high CPS and TPS (CPS: 3, 75, 95%; TPS: 2, 60, 90%). On an exploratory analysis, as the CPS or TPS threshold increased, there was a trend towards worse survival.
MPM has a high frequency of PD-L1 expression, which may be associated with more aggressive tumor biology. These data provide the foundation for continued evaluation of checkpoint inhibition in patients with MPM.